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Search Results: 1 - 10 of 192248 matches for " Beth D. Jamieson "
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Overexpression of MicroRNAs from the miR-17-92 Paralog Clusters in AIDS-Related Non-Hodgkin's Lymphomas
Dharma R. Thapa,Xinmin Li,Beth D. Jamieson,Otoniel Martínez-Maza
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020781
Abstract: Individuals infected by HIV are at an increased risk for developing non-Hodgkin's lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.
The Dual Impact of HIV-1 Infection and Aging on Na?ve CD4+ T-Cells: Additive and Distinct Patterns of Impairment
Tammy M. Rickabaugh,Ryan D. Kilpatrick,Lance E. Hultin,Patricia M. Hultin,Mary Ann Hausner,Catherine A. Sugar,Keri N. Althoff,Joseph B. Margolick,Charles R. Rinaldo,Roger Detels,John Phair,Rita B. Effros,Beth D. Jamieson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016459
Abstract: HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As na?ve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA+CD31+ and CD45RA+CD31-) within the na?ve CD4+ T-cell compartment in young (20–32 years old) and older (39–58 years old), ART-na?ve, HIV-1 seropositive individuals within 1–3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA+CD31+CD4+ and CD45RA+CD31-CD4+ T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA+CD31+CD4+ T-cells two years post-ART, but minimal reconstitution of the CD45RA+CD31-CD4+ subset, which could impair de novo immune responses. For both ART-na?ve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4+ T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults.
Natural Killer T Cells in Advanced Melanoma Patients Treated with Tremelimumab
F. Javier Ibarrondo, Otto O. Yang, Thinle Chodon, Earl Avramis, Yohan Lee, Hooman Sazegar, Jason Jalil, Bartosz Chmielowski, Richard C. Koya, Ingrid Schmid, Jesus Gomez-Navarro, Beth D. Jamieson, Antoni Ribas, Bego?a Comin-Anduix
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076829
Abstract: A significant barrier to effective immune clearance of cancer is loss of antitumor cytotoxic T cell activity. Antibodies to block pro-apoptotic/downmodulatory signals to T cells are currently being tested. Because invariant natural killer T cells (iNKT) can regulate the balance of Th1/Th2 cellular immune responses, we characterized the frequencies of circulating iNKT cell subsets in 21 patients with melanoma who received the anti-CTLA4 monoclonal antibody tremelimumab alone and 8 patients who received the antibody in combination with MART-126–35 peptide-pulsed dendritic cells (MART-1/DC). Blood T cell phenotypes and functionality were characterized by flow cytometry before and after treatment. iNKT cells exhibited the central memory phenotype and showed polyfunctional cytokine production. In the combination treatment group, high frequencies of pro-inflammatory Th1 iNKT CD8+ cells correlated with positive clinical responses. These results indicate that iNKT cells play a critical role in regulating effective antitumor T cell activity.
Differential Blood and Mucosal Immune Responses against an HIV-1 Vaccine Administered via Inguinal or Deltoid Injection
Otto O. Yang, F. Javier Ibarrondo, Charles Price, Lance E. Hultin, Julie Elliott, Patricia M. Hultin, Roger Shih, Mary Ann Hausner, Hwee L. Ng, Jennifer Hoffman, Beth D. Jamieson, Peter A. Anton
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088621
Abstract: Mucosal immunity is central to sexual transmission and overall pathogenesis of HIV-1 infection, but the ability of vaccines to induce immune responses in mucosal tissue compartments is poorly defined. Because macaque vaccine studies suggest that inguinal (versus limb) vaccination may better target sexually-exposed mucosa, we performed a randomized, double-blinded, placebo-controlled Phase I trial in HIV-1-uninfected volunteers, using the recombinant Canarypox (CP) vaccine vCP205 delivered by different routes. 12 persons received vaccine and 6 received placebo, divided evenly between deltoid-intramuscular (deltoid-IM) or inguinal-subcutaneous (inguinal-SC) injection routes. The most significant safety events were injection site reactions (Grade 3) in one inguinal vaccinee. CP-specific antibodies were detected in the blood of all 12 vaccinees by Day 24, while HIV-1-specific antibodies were observed in the blood and gut mucosa of 1/9 and 4/9 evaluated vaccinees respectively, with gut antibodies appearing earlier in inguinal vaccinees (24–180 versus 180–365 days). HIV-1-specific CD8+ T lymphocytes (CTLs) were observed in 7/12 vaccinees, and blood and gut targeting were distinct. Within blood, both deltoid and inguinal responders had detectable CTL responses by 17–24 days; inguinal responders had early responses (within 10 days) while deltoid responders had later responses (24–180 days) in gut mucosa. Our results demonstrate relative safety of inguinal vaccination and qualitative or quantitative compartmentalization of immune responses between blood and gut mucosa, and highlight the importance of not only evaluating early blood responses to HIV-1 vaccines but also mucosal responses over time. Trial Registration ClinicalTrials.gov NCT00076817
The Use of Neural Networks and Genetic Algorithms for Design of Groundwater Remediation Schemes
Z. Rao,D. G. Jamieson
Hydrology and Earth System Sciences (HESS) & Discussions (HESSD) , 1997,
Abstract: The increasing incidence of groundwater pollution has led to recognition of a need to develop objective techniques for designing reniediation schemes. This paper outlines one such possibility for determining how many abstraction/injection wells are required, where they should be located etc., having regard to minimising the overall cost. To that end, an artificial neural network is used in association with a 2-D or 3-D groundwater simulation model to determine the performance of different combinations of abstraction/injection wells. Thereafter, a genetic algorithm is used to identify which of these combinations offers the least-cost solution to achieve the prescribed residual levels of pollutant within whatever timescale is specified. The resultant hybrid algorithm has been shown to be effective for a simplified but nevertheless representative problem; based on the results presented, it is expected the methodology developed will be equally applicable to large-scale, real-world situations.
Copy Number Variation of KIR Genes Influences HIV-1 Control
Kimberly Pelak,Anna C. Need,Jacques Fellay,Kevin V. Shianna,Sheng Feng,Thomas J. Urban,Dongliang Ge,Andrea De Luca,Javier Martinez-Picado,Steven M. Wolinsky,Jeremy J. Martinson,Beth D. Jamieson,Jay H. Bream,Maureen P. Martin,Persephone Borrow,Norman L. Letvin,Andrew J. McMichael,Barton F. Haynes,Amalio Telenti,Mary Carrington,David B. Goldstein,Galit Alter
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001208
Abstract: A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3DS1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028), as does an increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for both receptors (p = 0.0015). We further provide functional data that demonstrate that NK cells from individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection.
Active Ranking using Pairwise Comparisons
Kevin G. Jamieson,Robert D. Nowak
Mathematics , 2011,
Abstract: This paper examines the problem of ranking a collection of objects using pairwise comparisons (rankings of two objects). In general, the ranking of $n$ objects can be identified by standard sorting methods using $n log_2 n$ pairwise comparisons. We are interested in natural situations in which relationships among the objects may allow for ranking using far fewer pairwise comparisons. Specifically, we assume that the objects can be embedded into a $d$-dimensional Euclidean space and that the rankings reflect their relative distances from a common reference point in $R^d$. We show that under this assumption the number of possible rankings grows like $n^{2d}$ and demonstrate an algorithm that can identify a randomly selected ranking using just slightly more than $d log n$ adaptively selected pairwise comparisons, on average. If instead the comparisons are chosen at random, then almost all pairwise comparisons must be made in order to identify any ranking. In addition, we propose a robust, error-tolerant algorithm that only requires that the pairwise comparisons are probably correct. Experimental studies with synthetic and real datasets support the conclusions of our theoretical analysis.
Comparison of Multimodality Image-Based Volumes in Preclinical Tumor Models Using In-Air Micro-CT Image Volume as Reference Tumor Volume  [PDF]
Yongsook C. Lee, Gary D. Fullerton, Beth A. Goins
Open Journal of Medical Imaging (OJMI) , 2015, DOI: 10.4236/ojmi.2015.53016
Abstract: Purpose: Changes in tumor volume are used for therapy response monitoring in preclinical studies. Unlike prior studies, this article introduces in-air micro-computed tomography (micro-CT) image volume as reference tumor volume in rodent tumor models. Tumor volumes determined using imaging modalities such as magnetic resonance imaging (MRI), micro-CT and ultrasound (US), and with an external caliper are compared with the reference tumor volume. Materials and Methods: In vivo MR, US and micro-CT imaging was performed 4, 6, 9, 11 and 13 days after tumor cell inoculation into nude rats. On the day of the imaging study, in vivo caliper measurements were also made. After in vivo imaging, tumors were excised followed by in-air micro-CT imaging and ex vivo caliper measurements of excised tumors. The in-air micro-CT image volume of excised tumors was determined as reference tumor volume. Then tumor volumes were calculated using formula V = (π/6) × a × b × c, where a, b and c are maximum diameters in three perpendicular dimensions determined by the three image modalities and caliper, and compared with reference tumor volume by linear regression analysis as well as Bland-Altman plots. Results: The correlation coefficients (R2) of the regression lines for in vivo tumor volumes measured by the three imaging modalities were 0.9939, 0.9669 and 0.9806 for MRI, US and micro-CT respectively. For caliper measurements, the coefficients were 0.9274 and 0.9819 for caliperin vivo and caliperex vivo respectively. In Bland-Altman plots, the average of tumor volume difference from reference tumor volume (bias) was significant for caliper and micro-CT, but not for MRI and US. Conclusion: Using the in-air micro-CT image volume as reference tumor volume, tumor volume measured by MRI was the most accurate among the three imaging modalities. In vivo caliper volume measurements showed unreliability while ex vivo caliper measurements reduced errors.
Copy Number Variation of KIR Genes Influences HIV-1 Control
Kimberly Pelak equal contributor,Anna C. Need equal contributor,Jacques Fellay equal contributor,Kevin V. Shianna,Sheng Feng,Thomas J. Urban,Dongliang Ge,Andrea De Luca,Javier Martinez-Picado,Steven M. Wolinsky,Jeremy J. Martinson,Beth D. Jamieson,Jay H. Bream,Maureen P. Martin,Persephone Borrow,Norman L. Letvin,Andrew J. McMichael,Barton F. Haynes,Amalio Telenti,Mary Carrington,David B. Goldstein,Galit Alter ,on behalf of NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
PLOS Biology , 2011, DOI: 10.1371/journal.pbio.1001208
Abstract: A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3DS1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028), as does an increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for both receptors (p = 0.0015). We further provide functional data that demonstrate that NK cells from individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection.
Hepatitis C Virus (HCV): Prevalence in a Gynecological Urgent Care Clinic Population
J. Adusumalli,E. A. Bonney,L. Odenat,D. J. Jamieson
Infectious Diseases in Obstetrics and Gynecology , 2004, DOI: 10.1080/1064744042000210393
Abstract: Objective: To determine the prevalence of hepatitis C virus (HCV) among women seeking urgent gynecological care.
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