Polymorphonuclear leukocytes (PMN) accumulating in airways of patients with cystic fibrosis (CF) as a response to chronic endobronchial bacterial lung infection, release lysosomal serine proteinases such as PMN-elastase at concentrations of approximately 0.5 microM to 5 microM into the airway lumen. Immunohistology of CF lung material and fluorescence activated cell sorter analysis of sequential CF bronchoalveolar lavages demonstrated loss of the CD4 and CD8 Ag on CD3+ T lymphocytes in sputum-filled airways. In 10 CF sputum samples 1.0%, 19.1%, and 15.7% of all CD3+ T lymphocytes expressed CD4, CD8, and CD2, respectively. Incubation of CF sputum supernatant fluids with peripheral blood T lymphocytes resulted in total reduction of CD4 and CD8 but not CD2. Addition of alpha 1-proteinase inhibitor abolished surface Ag cleavage completely. Purified PMN-elastase and cathepsin G cleaved CD2, CD4, and CD8 on peripheral blood T lymphocytes at proteinase concentrations of 0.83 to 8.3 microM in a dose-dependent manner. Cleaved CD4 and CD8 were reexpressed on the surface of T lymphocytes after 24 h in the absence of PMN-elastase. Incubation of a CD4+ T cell clone with PMN-elastase lead to a significant reduction of cytotoxicity toward target cells and significantly reduced IL-2 and IL-4 production. The results suggest a temporary functional impairment of T lymphocytes in foci of high inflammation characterized by stimulated PMN, which may lower tissue destruction.
This paper reports on a quantitative study of prioritisation of biodiversity amongst small‐ to medium‐sized enterprise (SME) leaders. Existing research indicates that value orientation impacts propensity for pro‐environmental behaviours. However, as biodiversity loss remains inadequately addressed, this study employs the value‐belief‐norm framework to explore how leaders with strong biospheric and altruistic (collectively termed ‘bigger‐than‐self’) value orientations perceive their responsibility for biodiversity loss in comparison with climate change and, using an adaptation of the Global Reporting Initiative standards, how biodiversity is prioritised against other areas of environmental sustainability in their businesses. Surveying 61 SME leaders, primarily in the South‐West UK, it was found that biodiversity is often considered of low priority compared with factors such as energy, waste, materials and emissions. Analysis also indicates that these leaders feel less responsibility for biodiversity than for climate change demonstrating that, even where bigger‐than‐self values dominate, there is a need for higher prioritisation of biodiversity amongst SMEs.
Scleroderma is one of the main clinical features of chronic graft-versus-host disease (cGVHD), in which donor immune cells react against host tissues after allogeneic hematopoietic stem cell transplant. It has been reported that interferon (IFN)-g released by donor T cells promotes infiltration of donor T cells themselves into the skin, and mediates production of transforming growth factor (TGF)-b from macrophages in the pathogenesis of sclerodermatous cGVHD. To investigate the roles of host keratinocytes, which are the targets for donor T cells, in skin fibrosis of cGVHD, we established a new murine model of sclerodermatous cGVHD using transgenic mice that express membrane-bound chicken ovalbumin (OVA) under the control of a keratin 14 promoter (K14-mOVA Tg mice), which present cGVHD-like scleroderma 28 days after the transfer of OVA-specific CD8 T cells (OT-I cells). IFNg -/-OT-I cells-transferred K14-mOVA Tg mice developed significantly milder scleroderma (clinical score, 5.9AE0.64, P<0.01), which were also assessed by dermal thickness, the numbers of infiltrating a-smooth muscle actin-positive myofibroblasts and hydroxyproline contents, than wild-type OT-I cell-transferred mice (clinical score, 3.1AE0.62). Moreover, mRNA expression of TGF-b were significantly lower in both total skin samples and epidermal keratinocytes from IFNg -/-OT-I cell-transferred K14-mOVA Tg mice than in those of OT-I celltransferred mice. Primary murine keratinocytes undergoing apoptosis produced more amount of TGF-b when stimulated by 2AE12.15 pg/ml, measured by an enzyme-linked immunosorbent assay, P<0.01) as well as when treated with an apoptosis-induce agent (AT101; 107.8AE12.18 pg/ml, P<0.01), compared to untreated keratinocytes (17.8AE5.5 pg/ml) and borate-treated keratinocytes undergoing necrosis (0 pg/ml). Collectively, TGF-b produced by keratinocytes undergoing IFN-g-induced apoptosis is implicated in the pathogenesis of sclerodermatous cGVHD.
Background
Miami-Dade County (MDC) has the highest rate of new HIV diagnoses in the United States (US), with highest incidence among Black and Latino men who have sex with men (MSM). Immigrants may be especially vulnerable to HIV acquisition and may lack or avoid accessible sexual health services. The University of Miami Mobile PrEP (MP) Clinic provides sexual health services including STI and HIV testing as well as PrEP initiation and follow-up in four highly impacted areas of MDC. The majority of MP clients are immigrant Latino MSM. We evaluated sexual healthcare access, preferences, and facilitators or barriers to receiving sexual health services through non-traditional platforms.
Methods
A brief survey was offered to clients at four MP locations from September 2020 to June 2021. Multiple-choice questions addressed healthcare access, usage, and experience as well as preferences for service receipt including home-based, mobile clinic, and telehealth options. Brief qualitative short answer responses were also elicited. Results were tabulated and presented descriptively.
Results
A total of 115 clients were surveyed. Mean age was 36; 82.6% identified as male. Most respondents were either White/Caucasian (56.5%) or Black/African-American (19.1%) and 78 (67.8%) identified as Hispanic/Latinx. Of the 66% that reported being born outside the US, 34.2% had immigrated in the past 5 years. Only 41.7% of respondents had a primary care provider. Before coming to the MP clinic, 27% had not been seen for sexual health services in over 2 years. Most clients indicated satisfaction with MP services. The most important characteristics for a care site identified included comfort with staff, location, and affordability. 43.5% preferred a clinic time outside of 9am-5pm. Only 13% of clients preferred home-based labs using a self-collection kit with a majority preference for in-person follow-up at the MP clinic.
Conclusion
Key populations at risk for HIV infection including immigrants and Black and Latino MSM may experience barriers to traditional clinic care. Clients expressed satisfaction with MP services, and a preference for clinic-collected rather than self-collected specimens. Further research to tailor service delivery to client preferences is needed.
Disclosures
All Authors: No reported disclosures
Incidence of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) has declined by more than 95% since initiation of the elimination program in 2005. As the ISC transitions to the post-elimination surveillance phase, an accurate measurement of human-vector contact is needed to assure long-term success. To develop this tool, we identified PagSP02 and PagSP06 from saliva of Phlebotomus argentipes, the vector of Leishmania donovani in the ISC, as immunodominant proteins in humans. We also established the absence of cross-reactivity with Ph. papatasi saliva, the only other human-biting sand fly in the ISC. Importantly, by combining recombinant rPagSP02 and rPagSP06 we achieved greater antibody recognition and specificity than single salivary proteins. The Receiver Operating Characteristics curve for rPagSP02 + rPagSP06 predicts exposure to Ph. argentipes bites with 90% specificity and 87% sensitivity compared to negative control sera (P >0.0001). Overall, rPagSP02 + rPagSP06 provides an effective surveillance tool for monitoring vector control efforts post-VL elimination.
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