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Search Results: 1 - 10 of 300290 matches for " Jeremy J. Martinson "
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Investigation of Association between PFO Complicated by Cryptogenic Stroke and a Common Variant of the Cardiac Transcription Factor GATA4
Mahdi Moradi Marjaneh, Edwin P. Kirk, Maximilian G. Posch, Cemil Ozcelik, Felix Berger, Roland Hetzer, Robyn Otway, Tanya L. Butler, Gillian M. Blue, Lyn R. Griffiths, Diane Fatkin, Jeremy J. Martinson, David S. Winlaw, Michael P. Feneley, Richard P. Harvey
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020711
Abstract: Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke.
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.
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.
LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection
Arman A. Bashirova equal contributor,Enrique Martin-Gayo equal contributor,Des C. Jones equal contributor,Ying Qi,Richard Apps,Xiaojiang Gao,Patrick S. Burke,Craig J. Taylor,Jerome Rogich,Steven Wolinsky,Jay H. Bream,Priya Duggal,Shehnaz Hussain,Jeremy Martinson,Amy Weintrob,Gregory D. Kirk,Jacques Fellay,Susan P. Buchbinder,James J. Goedert,Steven G. Deeks,Florencia Pereyra,John Trowsdale,Mathias Lichterfeld,Amalio Telenti,Bruce D. Walker,Rachel L. Allen,Mary Carrington,Xu G. Yu
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004196
Abstract: Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10?2). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10?11–10?9) and African (p = 10?5–10?3) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.
Cotrimoxazole Prophylaxis and Tuberculosis Risk among People Living with HIV
Christopher J. Hoffmann, Richard E. Chaisson, Neil A. Martinson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0083750
Abstract: Objectives Many randomized and cohort studies have reported a survival benefit with cotrimoxazole prophylaxis without detecting a difference in tuberculosis (TB) incidence by cotrimoxazole status. However, several in vitro studies have reported that cotrimoxazole possesses anti-TB activity. We sought to compare TB incidence and TB diagnostic yield by cotrimoxazole use among participants in a well characterized cohort of HIV-infected adults living in a high TB prevalence region. Methods We analyzed prospective data from a long-term longitudinal cohort of adults receiving HIV care and TB investigations in Soweto, South Africa. Using longitudinal analysis, we compared total and laboratory confirmed TB incidence by cotrimoxazole status as well as all-cause mortality. In addition, we compared TB culture results by cotrimoxazole status. Results In a multivariable analysis, adjusted for sex, body mass index, WHO clinical stage, time-updated CD4 count, and antiretroviral therapy status, we observed an association between cotrimoxazole and an increase in TB incidence (hazard ratio 1.7, 95% CI: 1.2, 2.2). However, when restricted to laboratory-confirmed TB, there was no association between cotrimoxazole and TB incidence (hazard ratio: 0.97, 95% CI: 0.39, 2.4). In TB cases, we found no difference in the proportion of positive sputum cultures or days to culture positivity by cotrimoxazole status. Cotrimoxazole was associated with a reduction in mortality. Conclusions In this cohort with a mortality benefit from cotrimoxazole, we found an increased risk of all TB among individuals using cotrimoxazole, likely a result of residual confounding, but no association between use of cotrimoxazole and laboratory-confirmed TB. Cotrimoxazole did not compromise TB diagnosis.
A Within-Host Model of Dengue Infection with a Non-Constant Monocyte Production Rate  [PDF]
Jeremy J. Thibodeaux, Michael Hennessey
Applied Mathematics (AM) , 2016, DOI: 10.4236/am.2016.718187
Abstract: In this paper we modify previous models to develop a new model of within-host dengue infection without the assumption that monocyte production is constant. We show that this new model exhibits behavior not seen in previous models. We then proceed by obtaining an expression for the net reproductive rate of the virus and thus establish a stability result. We also perform a sensitivity analysis to test various treatment strategies and find that two strategies might be fruitful. One is the reduction of the infection rate of monocytes by viruses and the other, more effective, theoretical approach is to reduce the number of new viruses per infected monocyte.
Common Genetic Variation and the Control of HIV-1 in Humans
Jacques Fellay equal contributor,Dongliang Ge equal contributor,Kevin V. Shianna,Sara Colombo,Bruno Ledergerber,Elizabeth T. Cirulli,Thomas J. Urban,Kunlin Zhang,Curtis E. Gumbs,Jason P. Smith,Antonella Castagna,Alessandro Cozzi-Lepri,Andrea De Luca,Philippa Easterbrook,Huldrych F. Günthard,Simon Mallal,Cristina Mussini,Judith Dalmau,Javier Martinez-Picado,José M. Miro,Niels Obel,Steven M. Wolinsky,Jeremy J. Martinson,Roger Detels,Joseph B. Margolick,Lisa P. Jacobson,Patrick Descombes,Stylianos E. Antonarakis,Jacques S. Beckmann,Stephen J. O'Brien,Norman L. Letvin,Andrew J. McMichael,Barton F. Haynes,Mary Carrington,Sheng Feng,Amalio Telenti ,David B. Goldstein ,NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
PLOS Genetics , 2009, DOI: 10.1371/journal.pgen.1000791
Abstract: To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.
Resident accuracy in locating the common femoral vein in normal weight vs. obese patients  [PDF]
Leigh Patterson, Jeremy J. Bennett, Kori Brewer
Open Journal of Clinical Diagnostics (OJCD) , 2013, DOI: 10.4236/ojcd.2013.33018
Abstract: Objectives: Ultrasound guidance increases the success of internal jugular central venous catheter (CVC) placement. The common femoral vein (CFV) is considered an easier site and physicians frequently place CFV CVCs using anatomical landmark guidance. No research has demonstrated the effect of patient weight on placement of a femoral CVC. The authors hypothesized that resident physicians could determine by anatomical landmarks the insertion site of a femoral CVC in normal and overweight adults. Methods: Investigators consented adult patients in the Emergency Department to serve as study models. Patients were grouped by BMI: Normal (BMI < 25) and Overweight (BMI > 25). PGYI-III Emergency Medicine residents who volunteered to participate were included. Residents inspected and palpated the inguinal regions on a patient and marked the patient’s skin directly over the CFV. A faculty member assessed success using a 10 MHz linear probe (Sonosite Micro Maxx) centered over the mark. The attempt was successful if the mark was directly over the CFV and unsuccessful if distal, lateral, or medial to the CFV. Results: Nineteen residents (6 PGYI, 7 PGY II, and 6 PGYIII) assessed 17 patients. There were 43 attempts on Normal patients and 57 attempts on Overweight patients. The success rate on Normal patients was 74% and on Overweight patients was 42% (p = 0.0021). Conclusion: Residents were more successful in correctly identifying the CFV by anatomical landmarks in Normal patients. Training year had no effect on success. Ultrasound guidance may increase the success rate of placing a femoral CVC in patients with BMI > 25.
Pathoecology of Chiribaya parasitism
Martinson, Elizabeth;Reinhard, Karl J;Buikstra, Jane E;Cruz, Katharina Dittmar de la;
Memórias do Instituto Oswaldo Cruz , 2003, DOI: 10.1590/S0074-02762003000900029
Abstract: the excavations of chiribaya culture sites in the osmore drainage of southern peru focused on the recovery of information about prehistoric disease, including parasitism. the archaeologists excavated human, dog, guinea pig, and llama mummies. these mummies were analyzed for internal and external parasites. the results of the analysis and reconstruction of prehistoric life from the excavations allows us to interpret the pathoecology of the chiribaya culture.
Pathoecology of Chiribaya parasitism
Martinson Elizabeth,Reinhard Karl J,Buikstra Jane E,Cruz Katharina Dittmar de la
Memórias do Instituto Oswaldo Cruz , 2003,
Abstract: The excavations of Chiribaya culture sites in the Osmore drainage of southern Peru focused on the recovery of information about prehistoric disease, including parasitism. The archaeologists excavated human, dog, guinea pig, and llama mummies. These mummies were analyzed for internal and external parasites. The results of the analysis and reconstruction of prehistoric life from the excavations allows us to interpret the pathoecology of the Chiribaya culture.
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