Immunology presentation at the 1990 NASA/NSF Antarctica Biomedical Science Working Group

An overview of methodology used for determining human in vitro lymphocyte activation, proliferation and effector cell function was presented and results of previous manned space flight immunology studies from Apollo through Shuttle were reviewed. Until the Shuttle era, lymphocyte assays were not very sensitive and had such large variations among normal subjects that it was difficult to define a consistent effect of space flight. More sensitive assay, however, even with Shuttle missions as brief as 6 days indicate depressed T-cell proliferative responses are routinely observed following space flight. Using a slight modification of the Shuttle assay, five different human stress-immunology models have been studied over the last 6 years in our lab. These have included: academic examinations of medical students having blood drawn during major test periods on three separate groups of first year students and two hypoxia studies (at 25,000 feet in a 6 week chamber ascent to the equivalent of Mount Everest and twice on Pikes Peak at 14,000 feet). These studies are particularly pertinent to Antarctica, since the altitude equivalent of 11,000 feet at the South Pole may affect some of the variables that are being measured in immunology, physiology or cognitive studies. An extravehicular study was performed drawing blood from 35 individuals before and immediately following a chamber exposure study. Preliminary results from 30 Shuttle astronauts investigated immunophenotype analysis and the role of a novel monocyte population in modulating the previously observed suppressed in vitro immune function. The results of the Air Force Academy cadet stress study were also presented

Portable dynamic fundus instrument

A portable diagnostic image analysis instrument is disclosed for retinal funduscopy in which an eye fundus image is optically processed by a lens system to a charge coupled device (CCD) which produces recordable and viewable output data and is simultaneously viewable on an electronic view finder. The fundus image is processed to develop a representation of the vessel or vessels from the output data

Microwave pyrolysis of Laminaria digitata to produce unique seaweed-derived bio-oils

Microwave pyrolysis has become an attractive form of processing technology to generate bio-oil, bio-char and syngas from different biomass feedstocks. In this study, microwave pyrolysis was performed on the UK native seaweed Laminaria digitata and its extract residue from a bio-refinery process. Pyrolysis of these two feedstocks was successfully achieved without the requirement of microwave susceptors, as pelletizing the biomass was sufficient to allow microwave pyrolysis to occur. It was found that average energy requirements as low as 1.84–2.83 kJ g−1 were required to pyrolyse 55–70% of both feedstocks and bio-oil yields of 5–8% and 10–14% for native and extraction residue L. digitata were produced, respectively. Maximum microwave pyrolysis processing times were in the order of 200 s. The bio-oil generated from both feedstocks contained no phenolic based compounds, but a greater number of nitrogen-containing compounds and compounds derived from macroalgal polysaccharides. Yields of certain compounds differed in bio-oils generated from the two L. digitata feedstocks, however it was observed that specific energy did not have a direct influence on bio-oil compound yield. Furthermore, the identification of a particular nitrogen-containing compound L-Proline, 1-methyl-5-oxo-, methylester is thought to be a unique product of microwave pyrolysis when carbon-based additives are avoided

FEV1 over time in patients with connective tissue disease-related bronchiolitis

SummaryBackgroundFibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown.MethodsWe analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB).ResultsOf 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis (n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV1 %pred at all times. There were no significant differences in FEV1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward.ConclusionSubjects with CTD-related CB had lower FEV1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV1 %pred remained stable over time in both groups regardless of therapy received

Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple Myeloma: A CIBMTR Analysis.

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (-Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P \u3c .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P \u3c .001) and 72% versus 85% (P \u3c .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to HRM, higher stage, less than a CR pretransplant, lack of post-transplant therapy, and African American race were associated with worse OS. In conclusion, we show HRM patients achieve similar day 100 post-transplant responses compared with non-HRM patients, but these responses are not sustained. Post-transplant therapy appeared to improve the poor outcomes of HRM

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Celtic pilgrimage, past and present: from historical geography to contemporary embodied practices

Perigrinatio, the Latin term for pilgrimage was at the heart of the medieval Celtic church, but was this was understood and practised not only as a journey to a shrine, but more broadly as a spiritual journey, which could lead to an isolated hermitage or peripatetic evangelistic mission. In this paper, we outline the beliefs and practices of the broad assemblage known as the Celtic church, particularly the interleaving of pilgrimage, asceticism and landscape poetics, and how these have informed continued and renewed pilgrimage practices to sites of the early Celtic church by particular denominations, ecumenical groups and those interested in broader spiritualities. These sacred mobilities are explored through vignettes of embodied-emotionalspiritual practices situated in the landscapes and faith communities of Lough Derg,Ireland and the Isle of Man. They share geographical marginality, a focus on multiple Celtic saints and an enduring belief in the immanence of God, expressed through embodied spiritual practice in the landscape. However, they differ widely in matters of institutionalised structure, regulation, discursive scripting and gendered hierarchy, reflecting situated and denominational preferences for the ascetic and aesthetic spiritual legacies of the medieval Celtic church

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

A Cell/Cilia Cycle Biosensor for Single-Cell Kinetics Reveals Persistence of Cilia after G1/S Transition Is a General Property in Cells and Mice

The cilia and cell cycles are inextricably linked. Centrioles in the basal body of cilia nucleate the ciliary axoneme and sequester pericentriolar matrix (PCM) at the centrosome to organize the mitotic spindle. Cilia themselves respond to growth signals, prompting cilia resorption and cell cycle re-entry. We describe a fluorescent cilia and cell cycle biosensor allowing live imaging of cell cycle progression and cilia assembly and disassembly kinetics in cells and inducible mice. We define assembly and disassembly in relation to cell cycle stage with single-cell resolution and explore the intercellular heterogeneity in cilia kinetics. In all cells and tissues analyzed, we observed cilia that persist through the G1/S transition and into S/G2/M-phase. We conclude that persistence of cilia after the G1/S transition is a general property. This resource will shed light at an individual cell level on the interplay between the cilia and cell cycles in development, regeneration, and disease. The cilia and cell cycles are fundamental processes coupled through shared machinery. Ford et al. develop and characterize a multicistronic biosensor that can simultaneously label the cell and cilia cycles in mice, enabling live imaging studies of their kinetics

Heterostructures for Optical Devices

Contains research objectives and reports on eight research projects.Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAALO3-89-C-0001)National Science Foundation (Grant EET 87-03404)Charles Stark Draper Laboratory (Contract DL-H-315251)Xerox Corporation FellowshipMIT Fund