68 research outputs found
The response of the lymphatic endothelium to inflammation and infection in in vitro and in vivo systems
No full textThe lymphatic endothelium is involved in the drainage of interstitial fluid and in the migration of immune cells like dendritic cells (DCs) from the periphery to draining lymph nodes (LNs). Tuberculosis has been declared a pandemic infectious disease accounting for more than 2 million deaths annually and is caused by the intracellular bacteria, Mycobacterium tuberculosis. The chronic inflammatory response to M. tuberculosis infection is characterized by the formation of granulomatous structures in the pulmonary compartments of infected individuals. These structures contain excess interstitial fluid and are enriched with immune cells including DCs. Therefore, the lymphatic vessels might play important roles in regulating drainage of fluid and migration of immune cells from granulomas to the draining LNs. My hypothesis was that there is an increased concentration of lymphatic vessels in these granulomatous structures and that the inflammatory environment including mycobacterial components present in granulomas and at other sites of infection elicit an inflammatory response from these lymphatic vessels which contribute to the overall immune response to M. tuberculosis infection. To address this hypothesis I have examined the distribution of lymphatic vessels in granulomatous and LN tissues obtained from nonhuman primates infected with M. tuberculosis and analyzed their expression of multiple chemokines and lymphatic markers. In addition, I evaluated the response of LECs to inflammatory mediators that included multiple TLR ligands, M. tuberculosis components and cytokines. I observed an association of lymphatic vessels with granulomas, and found that there was heterogeneity in the expression of chemokines and lymphatic markers by LECs in tissues. I also found that primary human LECs expressed multiple TLR molecules and responded to TLR ligands, cytokines and M. tuberculosis components by increasing expression of inflammatory chemokines, cytokines and adhesion molecules. These LECs also demonstrated phenotypic similarities with DCs. Overall my findings support the involvement of the lymphatic endothelium in the inflammatory immune response to pathogens like M. tuberculosis. From the perspective of public health relevance, these studies provide direction in the development of new therapeutic targets against M. tuberculosis infections and aid in the development of better adjuvants for vaccines for infectious diseases and cancers
Afferent and Efferent Interfaces of Lymph Nodes Are Distinguished by Expression of Lymphatic Endothelial Markers and Chemokines
No full textAffective Ecologies of Illness: Medical Humanities, Environment, and Resistance in Boyer’s The Undying and Khakpour’s Sick
No full textThis paper examines the convergence of medical humanities, affect theory and ecocriticism in Anne Boyer’s The Undying (2019) and Porochista Khakpour’s Sick (2018). Both memoirs disrupt dominant biomedical and neoliberal health narratives by foregrounding the lived experience of illness within broader contexts of environmental toxicity, gendered care work, and structural inequality. Through the lens of affect theory, the study highlights how pain, fatigue, and vulnerability function as politically charged affective states that resist clinical objectification. An ecocritical perspective further reveals how each author portrays the body as a site inscribed by ecological and institutional violence. Boyer’s lyrical critique of breast cancer treatment and Khakpour’s intimate depiction of chronic Lyme disease underscore how illness emerges from entanglements with capitalist, patriarchal, and toxic systems. Situated within the medical humanities, these memoirs utilize experimental narrative forms and emotionally resonant language to reclaim agency, redefine care, and assert the ethical urgency of storytelling amid environmental and bodily precarity.
 
Eliminating antibody polyreactivity through addition of N-linked glycosylation
No full textAntibody polyreactivity can be an obstacle to translating a candidate antibody into a clinical product. Standard tests such as antibody binding to cardiolipin, HEp-2 cells, or nuclear antigens provide measures of polyreactivity, but its causes and the means to resolve are often unclear. Here we present a method for eliminating antibody polyreactivity through the computational design and genetic addition of N-linked glycosylation near known sites of polyreactivity. We used the HIV-1-neutralizing antibody, VRC07, as a test case, since efforts to increase VRC07 potency at three spatially distinct sites resulted in enhanced polyreactivity. The addition of N-linked glycans proximal to the polyreactivity-enhancing mutations at each of the spatially distinct sites resulted in reduced antibody polyreactivity as measured by (i) anti-cardiolipin ELISA, (ii) Luminex AtheNA Multi-Lyte ANA binding, and (iii) HEp-2 cell staining. The reduced polyreactivity trended with increased antibody concentration over time in mice, but not with improved overall protein stability as measured by differential scanning calorimetry. Moreover, glycan proximity to the site of polyreactivity appeared to be a critical factor. The results provide evidence that antibody polyreactivity can result from local, rather than global, features of an antibody and that addition of N-linked glycosylation can be an effective approach to reducing antibody polyreactivity.</p
Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques
No full textPrevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1–specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8+ T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.Fil: Hessell, Ann J.. Oregon Health and Science University; Estados UnidosFil: Jaworski, Juan Pablo. Oregon Health and Science University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Epson, Erin. Oregon Health and Science University; Estados UnidosFil: Matsuda, Kenta. National Institutes of Health; Estados UnidosFil: Pandey, Shilpi. Oregon Health and Science University; Estados UnidosFil: Kahl, Christoph. Oregon Health and Science University; Estados UnidosFil: Reed, Jason. Oregon Health and Science University; Estados UnidosFil: Sutton, William F.. Oregon Health and Science University; Estados UnidosFil: Hammond, Katherine B.. Oregon Health and Science University; Estados UnidosFil: Cheever, Tracy A.. Oregon Health and Science University; Estados UnidosFil: Barnette, Philip T.. Oregon Health and Science University; Estados UnidosFil: Legasse, Alfred W.. Oregon Health and Science University; Estados UnidosFil: Planer, Shannon. Oregon Health and Science University; Estados UnidosFil: Stanton, Jeffrey J.. Oregon Health and Science University; Estados UnidosFil: Pegu, Amarendra. National Institutes of Health; Estados UnidosFil: Chen, Xuejun. National Institutes of Health; Estados UnidosFil: Wang, Keyun. National Institutes of Health; Estados UnidosFil: Siess, Don. Oregon Health and Science University; Estados UnidosFil: Burke, David. Oregon Health and Science University; Estados UnidosFil: Park, Byung S.. Oregon Health and Science University; Estados UnidosFil: Axthelm, Michael K. Oregon Health and Science University; Estados UnidosFil: Lewis, Anne. Oregon Health and Science University; Estados UnidosFil: Hirsch, Vanessa M.. National Institutes of Health; Estados UnidosFil: Graham, Barney S.. National Institutes of Health; Estados UnidosFil: Mascola, John R.. National Institutes of Health; Estados UnidosFil: Sacha, Jonah B.. Oregon Health and Science University; Estados UnidosFil: Haigwood, Nancy L.. Oregon Health and Science University; Estados Unido
Human Herpesvirus 8 Infects and Replicates in Primary Cultures of Activated B Lymphocytes through DC-SIGN
No full textСлоны и бубенчики: государства Мьянмы глазами итальянских путешественников XV в.
No full textThe paper deals with the images of Ava and Pegu, two powerful medieval states of present-day Myanmar, in the accounts made by two merchants from the Italian maritime republics: Niccolò de' Conti of Venice (1439) and Hieronimo di Santo Stefano of Genoa (1499). The author observes the means of portrayal of the Southeast Asian social and religious practices in these documents, highlights the late medieval Europeans' perception of the regional body culture. The article also examines how the traditional images of India (Indias) in the medieval discourse were influenced by the travellers’ personal experience and evolved towards a more realistic portrayal.В статье анализируются образы государств Авы и Пегу в двух отчетах, оставленных купцами из итальянских морских республик: венецианцем Никколо Конти (1439) и генуэзцем Иеронимо ди Санто Стефано (1499). Автор статьи рассматривает основные средства портретирования социальных и религиозных практик Юго-Восточной Азии в этих документах, показывает особенности восприятия телесной культуры региона человеком позднесредневекового Запада. В работе также прослеживается эволюция в средневековом дискурсе о Востоке укоренившихся образов Индии или Индий как таинственного края ойкумены в сторону более реалистичной картины под влиянием личного опыта путешественников
Elephants and Bells: The States of Myanmar in the Eyes of 15th Century Italian Travellers
No full textСтатья поступила в редакцию 13.03.2015 г.В статье анализируются образы государств Авы и Пегу в двух отчетах, оставленных купцами из итальянских морских республик: венецианцем Никколо Конти (1439)
и генуэзцем Иеронимо ди Санто Стефано (1499). Автор статьи рассматривает основные средства портретирования социальных и религиозных практик Юго-Восточной
Азии в этих документах, показывает особенности восприятия телесной культуры
региона человеком позднесредневекового Запада. В работе также прослеживается
эволюция в средневековом дискурсе о В остоке укоренившихся образов Индии или Индий как таинственного края ойкумены в сторону более реалистичной картины под влиянием личного опыта путешественников.The paper deals with the images of Ava and Pegu, two powerful medieval states of present-day Myanmar, in the accounts made by two merchants from the Italian maritime republics: Niccolò de' Conti of Venice (1439) and Hieronimo di Santo Stefano of Genoa (1499). The author observes the means of portrayal of the Southeast Asian social and religious practices in these documents, highlights the late medieval Europeans' perception of the regional body culture. The article also examines how the traditional images of India (Indias) in the medieval discourse were influenced by the travellers’ personal experience and evolved towards a more realistic portrayal
Modeling cumulative overall prevention efficacy for the VRC01 phase 2b efficacy trials
No full textThe Antibody Mediated Prevention trials are assessing whether intravenously-administered VRC01 (10 mg/kg or 30 mg/kg vs placebo) can prevent HIV infection. In a modeling exercise, we used two models to predict the overall prevention efficacy (PE) of each VRC01 dose in preventing HIV infection. For the first per-exposure PE model, parameters were estimated from studies where nonhuman primates (NHPs) were administered high-dose intra-rectal simian-human immunodeficiency virus challenge two days post-VRC01 infusion at various dosages (“NHP model”). To account for the fact that humans may require greater VRC01 concentration to achieve the same level of protection, we next assumed that a 5-fold greater VRC01 serum concentration would be needed to provide the same level of per-exposure PE as seen in the NHP data (“5-fold model”). For the 10 mg/kg regimen, the 5-fold and NHP models predict an overall PE of 37% and 64%, respectively; for the 30 mg/kg regimen, the two models predict an overall PE of 53% and 82%, respectively. Our results support that VRC01 may plausibly confer positive PE in the AMP trials. Given the lack of available knowledge and data to verify the assumptions undergirding our modeling framework, its quantitative predictions of overall PE are preliminary. Its current main applications are to supplement decisions to advance mAb regimens to efficacy trials, and to enable mAb regimen ranking by their potential for PE in humans
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