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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Parkinson's disease may be linked to defects in mitochondrial function. Mitochondrially transformed cells (cybrids) were created from Parkinson's disease patients or disease-free controls. Parkinson's disease cybrids had 26% less complex I activity, but maintained comparable basal calcium and energy levels. Parkinson's disease cybrids recovered from a carbachol-induced increase in cytosolic calcium 53% more slowly than controls even with lanthanum and thapsigargin blockade. Inhibition of complex I with the Parkinson's disease-inducing metabolite 1-methyl-4-phenylpyridinium (MPP+) similarly reduced the rate of recovery after carbachol. This MPP+-induced reduction in recovery rates was much more pronounced in control cybrids than in Parkinson's disease cybrids. Parkinson's disease cybrids had less carbonyl cyanide m-chlorophenylhydrazone-releasable calcium. Bypassing complex I with succinate partially restored Parkinson's disease cybrid, and MPP+ suppressed control cybrid recovery rates. The subtle alteration in calcium homeostasis of Parkinson's disease cybrids may reflect an increased susceptibility to cell death under circumstances not ordinarily toxic.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Grass and forage science 58 (2003), S. 0 
    ISSN: 1365-2494
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Kudzu [Pueraria lobata (Willd.) Ohwi.], a vigorous, perennial warm-season legume, grows widely throughout the south-eastern United States, predominantly as a volunteer species. It is tolerant of drought and acidic, infertile soils and may have potential as a low-input forage for livestock. A field experiment was undertaken to determine the effects of cutting date and frequency on yield and nutritive value of kudzu (20-year-old stand with no fertilizer or lime inputs) in central Georgia. The cutting treatments included an uncut control, and plots cut once (September), twice (July and September), and three times (June, July, and September) during the 1994 growing season. Dry matter (DM) production and forage quality were determined for total herbage, leaf and stem tissues from quadrat samples taken on all plots in June, July, September, and November (after a killing frost) in 1994, and in June, 1995. Total herbage and leaf DM production was highest for the three-harvest system and lowest in the no-cut control plots in 1994, but these results were reversed in the harvest made in 1995. Total herbage production and crude protein concentrations were similar in kudzu cut in the initial summer harvest (either June, July, or September) during the first year. Whole plant and stem in vitro dry matter digestibility (IVDMD) in these samples declined throughout the growing season, while leaf IVDMD was unchanged until the first frost. Kudzu has the potential to be a low-input forage for livestock, particularly as supplemental drought feed, or as a protein bank for summer or autumn grazing.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2494
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: The botanical composition, intake and digestibility of the diet consumed by 1-year-old weaner sheep grazing a native white grass plant community in the Falkland Islands was measured in five periods between June 1998 and March 1999. Five different sheep were used in each period. Two methods were used for estimating the botanical composition of the diet: plant cuticle patterns in the faeces of the sheep and the patterns of concentrations of n-alkanes in the faeces of sheep. These methods were used to predict the concentrations of C32- and C33-alkanes in the herbage to allow the estimation of herbage intake and digestibility using the n-alkane technique. It was concluded that the n-alkane technique gave more accurate estimates of diet composition based on the comparison with estimates of nutrient intake derived from liveweight gains of sheep. The dominant pasture species, Cortaderia pilosa, was the predominant species consumed during the cooler periods of the year. In the summer, when the highest liveweight gains of sheep occur, the proportion of fine grass species, including Poa spp., Festuca magellanica and Agrostis capillaris, and herbs and sedges in the diet was highest. Herbage intake was the highest during the summer periods when digestibility was also at its peak. Estimated nutritional deficiencies of metabolizable energy, crude protein, phosphorus and vitamin D3 that limit the growth and development of weaner sheep were evident for up to 9 months of the year. Targeted supplementation regimes that counter specific nutrient deficiencies could be developed on the basis of these results to address critical periods in the growth of young sheep.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd
    Cytopathology 12 (2001), S. 0 
    ISSN: 1365-2303
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  Effective treatment of haemophilic arthropathy requires a detailed evaluation of joint integrity. Methodological assessment of magnetic resonance imaging (MRI) scores are needed to assure reproducibility of measurements when comparing results of clinical trials conducted in different centres. We compared the reliability of two MRI scoring systems for assessment of haemophilic arthropathy: one progressive system that displays the most severe change and one additive system that depicts osteochondral and soft tissue-related changes. A total of 47 1.5 T MRI examinations of knees (n = 21) and ankles (n = 26) of 42 haemophilic boys, age range, 22 months to 18 years, performed at different centres (Toronto, n = 20, Europe, n = 12 and Denver, n = 15) were independently reviewed by four radiologists at two occasions. Twenty-two examinations were from children 〈9 years and 25 from children ≥9. Sagittal and coronal gradient-echo (MPGR, 3D FLASH with fat saturation, GRASS) images were obtained. The MRI examinations of the ankle and knee studies presented with osteochondral abnormalities in 38.5% and 23.8% of the cases respectively. The two scoring systems demonstrated an excellent inter-reader [progressive, 0.88; additive (A, e, s and h components), 0.86] and intra-reader [progressive, 0.92; additive (A, e, s and h components), 0.93] reliability using intraclass correlation coefficients (ICCs). Although ICCs were slightly higher for knees when compared with ankles, and for older children when compared with younger children, all values fell within excellent inter- and intra-reader reliability categories. The two MRI scoring systems demonstrated a comparable reliability. This result constitutes the basis for further development of a combined MRI scoring system for assessment of haemophilic arthropathy, which incorporates progressive and additive components.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  The international MRI expert subgroup of the International Prophylaxis Study Group (IPSG) has developed a consensus for magnetic resonance imaging (MRI) scales for assessment of haemophilic arthropathy. A MRI scoring scheme including a 10 step progressive scale and a 20 step additive scale with identical definitions of mutual steps is presented. Using the progressive scale, effusion/haemarthrosis can correspond to progressive scores of 1, 2, or 3, and synovial hypertrophy and/or haemosiderin deposition to 4, 5, or 6. The progressive score can be 7 or 8 if there are subchondral cysts and/or surface erosions, and it is 9 or 10 if there is loss of cartilage. Using the additive scale, synovial hypertrophy contributes 1–3 points to the additive score and haemosiderin deposition contributes 1 point. For osteochondral changes, 16 statements are evaluated as to whether they are true or false, and each true statement contributes 1 point to the additive score. The use of these two compatible scales for progressive and additive MRI assessments can facilitate international comparison of data and enhance the accumulation of experience on MRI scoring of haemophilic arthropathy.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2013-11-16
    Description: Immune tolerance remains the most promising yet elusive strategy for treating immune-mediated diseases. An experimental strategy showing promise in phase 1 clinical studies is the delivery of Ag cross-linked to apoptotic leukocytes using ethylene carbodiimide. This approach originated from demonstration of the profound tolerance-inducing ability of i.v. administered Ag-coupled splenocytes (Ag-SP) in mice, which has been demonstrated to treat T cell–mediated disorders including autoimmunity, allergy, and transplant rejection. Recent studies have defined the intricate interplay between the innate and adaptive immune systems in Ag-SP tolerance induction. Innate mechanisms include scavenger receptor–mediated uptake of Ag-SP by host APCs, Ag representation, and the required upregulation of PD-L1 expression and IL-10 production by splenic marginal zone macrophages leading to Ag-specific T cell regulation via the combined effects of cell-intrinsic anergy and regulatory T cell induction. In this paper, we discuss the history, advantages, current mechanistic understanding, and clinical potential of tolerance induction using apoptotic Ag-coupled apoptotic leukocytes.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 8
    Publication Date: 2018-03-07
    Description: The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies for human diseases. We identified Ig-like domain–containing receptor (ILDR)2 as a novel B7-like protein with robust T cell inhibitory activity, expressed in immune cells and in immune-privileged and inflamed tissues. A fusion protein, consisting of ILDR2 extracellular domain with an Fc fragment, that binds to a putative counterpart on activated T cells showed a beneficial effect in the collagen-induced arthritis model and abrogated the production of proinflammatory cytokines and chemokines in autologous synovial-like cocultures of macrophages and cytokine-stimulated T cells. Collectively, these findings point to ILDR2 as a novel negative regulator for T cells, with potential roles in the development of immune-related diseases, including autoimmunity and cancer.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 9
    Publication Date: 2018-03-07
    Description: ILDR2 is a member of the Ig superfamily, which is implicated in tricellular tight junctions, and has a putative role in pancreatic islet health and survival. We recently found a novel role for ILDR2 in delivering inhibitory signals to T cells. In this article, we show that short-term treatment with ILDR2-Fc results in long-term durable beneficial effects in the relapsing-remitting experimental autoimmune encephalomyelitis and NOD type 1 diabetes models. ILDR2-Fc also promotes transplant engraftment in a minor mismatch bone marrow transplantation model. ILDR2-Fc displays a unique mode of action, combining immunomodulation, regulation of immune homeostasis, and re-establishment of Ag-specific immune tolerance via regulatory T cell induction. These findings support the potential of ILDR-Fc to provide a promising therapeutic approach for the treatment of autoimmune diseases.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 10
    Publication Date: 2016-03-05
    Description: HIV-1 replication is concentrated within CD4 + T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (T FH ) within germinal centers (GC) is highly permissive to HIV-1. Whether GC T FH are the major HIV-1 virus–producing cells in vivo has not been established. In this study, we investigated T FH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC T FH (CXCR5 high PD-1 high ) and CXCR5 + programmed cell death-1 (PD-1) low cells were GFP + than non-GC T FH (CXCR5 + PD-1 intermediate ) or extrafollicular (EF) (CXCR5 – ) cells. When sorted prior to spinoculation, however, GC T FH were substantially more permissive than CXCR5 + PD-1 low or EF cells, suggesting that many GC T FH transition to a CXCR5 + PD-1 low phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1–infected individuals without AIDS revealed higher frequencies of HIV-1 RNA + cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1–infected individuals’ lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5 + CD4 + cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5 + subsets harbored 11–66-fold more HIV-1 RNA than CXCR5 – subsets, as determined by RT PCR. Thus, GC T FH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC T FH as the major HIV-1–producing cells in chronic asymptomatic HIV-1 infection.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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