| 1. |
- Duan, Wei-Ming
(författare)
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Immunological and Inflammtory Responses against Intrastriatal Neural Grafts in the Rat
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intracerebral neural transplantation offers a new strategy to combat Parkinson’s and Huntington’s diseases. However, a host immune response against a histoincompatible neural graft in the brain may jeopardize transplant survival. We transplanted dissociated mesencephalic tissue prepared from Sprague-Dawley (SD) (syngeneic), Lewis (allogeneic) rats or mice (xenogeneic), into 6-hydroxydopamine (6-OHDA) lesioned or normal striatum of SD rats. We addressed the following issues: (i) the survival of syngeneic, allogeneic and xenogeneic neural grafts at different time-points after transplantation and the time-pattern of inflammatory and immunological reactions against them. (ii) if a first intrastriatal neural allograft leads to rejection of a second genetically identical allograft. (iii) if neural allografts can survive in the hosts which are immunized using orthotopic skin allografts before and after intracerebral surgery. (iv) the importance of graft immunogenicity for graft survival by supplementing allogeneic neuronal cell suspension with allogeneic spleen cells from the same Lewis donor rats. (v) the impact of severe local inflammation induced by an intrastriatal injection of quinolinic acid on the survival of neural allografts. (vi) the effects of methylprednisolone on the survival of intrastriatal concordant neural xenografts from mice. The results show: (1) Syngeneic and allogeneic neural grafts can survive transplantation to the striatum for prolonged periods. The inflammatory or immunological responses against such grafts are only weak and transient. In contrast, concordant xenogeneic neural grafts are in most cases rejected rapidly. (2) Neural allografts are not rejected by a host which has already received genetically identical allografts before. (3) Neural allografts are rejected if the host is immunized by an orthotopic skin allograft 6 weeks prior to, at the same time as, or 2 weeks after, neural transplantation surgery. However, neural allografts are not always promptly rejected if the orthotopic skin grafting is performed 6 weeks after the neural transplantation, although there is a massive inflammatory and immunological response against them. By 12 weeks after skin grafting, most of these allografts are rejected. (4) Addition of allogeneic spleen cells increases the immunogenicity of neural allografts and leads to rejection of mixed allografts following transplantation. (5) Severe inflammation in the striatum induced by quinolinic acid injection does not result in the rejection of neural allografts. (6) Rejection of concordant neural xenografts can be prevented by systemic administration of a daily high dose of methylprednisolone. In conclusion, the brain is an immunologically privileged site, but this privilege is not absolute. In our animal model, intrastriatal neural allografts can achieve long-term survival probably due to a very low immunogenicity and lack of antigen presenting cells in the grafted neural tissue. Even if neural allografts are implanted in a brain region that is affected by severe inflammation, they survive without clear signs of rejection. Nevertheless, rejection of neural allografts can be induced if the hosts are efficiently immunized with the same alloantigens before or soon after transplantation, rather than at later time-points. Methylprednisolone can be used as an alternative immunosuppressive drug to prevent rejection of concordant intracerebral neural xenografts.
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| 2. |
- Gao, Ming-Wei, et al.
(författare)
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Power predictions for a pilot scale stirred ball mill
- 1996
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Ingår i: International Journal of Mineral Processing. - : Elsevier BV. - 0301-7516 .- 1879-3525. ; 44-45, s. 641-652
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Tidskriftsartikel (refereegranskat)abstract
- The capacity of a stirred ball mill to grind to a certain product size efficiently depends strongly on the power intensity in the milling chamber. The dependence of power intensity on stirrer speed, slurry density, bead density and the amount of dispersant added to the feed was investigated using a 6-litre 11-kW horizontal stirred ball mill fitted with perforated disks as stirrers. Dolomite was ground at a fixed volumetric flow rate, but with slurry densities ranging from 65 to 75 percent by weight, stirrer speeds from 805 to 2253 rpm, bead densities from 2.5 to 5.4 g/ml and the dispersant level from 0.5 to 1.5 percent of dry solids. Three levels of the four variables were used in 27 continuous milling tests, set up as one-third of a 34 factorial design. All factors affected the power draft in a highly significant way. Speed, and to a lesser extent slurry density, were the dominant factors with significant non-linear effects. A six-term model, incorporating all significant effects, predicted the experimental results with an accuracy of about 12%. Increasing the power accelerated size reduction dramatically with only a small change to the energy efficiency of the process.
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| 3. |
- Li, Wei, et al.
(författare)
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Uptake of Oxidized LDL by Macrophages Results in Partial Lysosomal Enzyme Inactivation and Relocation
- 1998
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 18:2, s. 177-84
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Tidskriftsartikel (refereegranskat)abstract
- The cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells might contribute to atherosclerosis by causing cell death, presumably by both apoptosis and necrosis. After its uptake into macrophage lysosomes by receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in ceroid-containing foam cells. We studied the influence of oxLDL on lysosomal enzyme activity and, in particular, on lysosomal membrane stability and the modulation of these cellular characteristics by HDL and vitamin E (vit-E). Unexposed cells and cells exposed to acetylated LDL (AcLDL) were used as controls. The lysosomal marker enzymes cathepsin L and N-acetyl-β-glucosaminidase (NAβGase) were biochemically assayed in J-774 cells after fractionation. Lysosomal integrity in living cells was assayed by the acridine orange (AO) relocation test. Cathepsin D was immunocytochemically demonstrated in J-774 cells and human monocyte-derived macrophages. We found that the total activities of NAβGase and cathepsin L were significantly decreased, whereas their relative cytosolic activities were enhanced, after oxLDL exposure. Labilization of the lysosomal membranes was further proven by decreased lysosomal AO uptake and relocation to the cytosol of cathepsin D, as estimated by light and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The results indicate that endocytosed oxLDL not only partially inactivates lysosomal enzymes but also destabilizes the acidic vacuolar compartment, causing relocation of lysosomal enzymes to the cytosol. Exposure to AcLDL resulted in its uptake with enlargement of the lysosomal apparatus, but the stability of the lysosomal membranes was not changed.
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