Comparison of various lazaroid compounds for protection against ischemic liver injury

Lazaroids are a group of 21-aminosteroids that lack steroid action but have a potent cytoprotective effect by inhibiting iron-dependent lipid peroxidation. However, there have been conflicting reports on the effectiveness and potency of the various lazaroid compounds. In this study, we compared the effectiveness of three major lazaroids on warm liver ischemia in dogs using a 2-hr hepatic vascular exclusion model. The agents were given to the animals intravenously for 30 min before ischemia. The animals were divided into 5 groups: Control (n=10), no treatment; Group F (n=6), U-74006F (10 mg/kg); Group G (n=6), U-74389G (10 mg/kg); Group A1 (n=6), U-74500A (10 mg/kg); Group A2 (n=6), U-74500A (5 mg/kg). The effect of treatment was evaluated by two-week animal survival, hepatic tissue blood flow, liver function tests, blood and tissue biochemistry, and histological analyses. Animal survival in all treated groups was significantly improved compared with the control (83-100% versus 30%). Elevation of liver enzymes after reperfusion was markedly attenuated in treated groups, except for an early significant increase in Group G. Postreperfusion hepatic tissue blood flow was much higher in all treated animals (50% of the preischemic level vs. 25% in the control). Lazaroids, particularly U-74500A at 5 mg/kg (Group A2), suppressed adenine nucleotide degradation during ischemia and enhanced the resynthesis of high-energy phosphates after reperfusion. Although structural abnormalities in postreperfusion liver tissues were markedly ameliorated in all treated groups, Group A2 showed significantly less neutrophil infiltration. Liver injury from warm ischemia and reperfusion was attenuated with all lazaroid compounds, of which U-74500A at 5 mg/kg exhibited the most significant protective activity

Isolation, phenotype, and allostimulatory activity of mouse liver dendritic cells

Donor liver-derived dendritic cells (DC) have recently been identified within various lymphoid and nonlymphoid tissues of organ allograft recipients, including nonimmunosuppressed mice transplanted with and permanently accepting major histocompatibility complex (MHC)-disparate hepatic allografts. These findings have raised questions about the basis of the tolerogenicity of the liver—and, in particular, about the properties of liver-derived DC. To study further the structure, immunophenotype and allostimu-latory activity of leukocytes resident in normal mouse (B10.BR; H-2k, I-Ek) liver, a procedure was developed to maximize the yield of viable, nonparenchymal cells (NPC) obtained following collagenase digestion of perfused liver fragments and density centrifugation (Per-coll). These cells comprised populations expressing lymphoid and myeloid cell surface antigens. As compared with spleen cells, they proved good allostimula-tors of naive (BIO; H-2b, I-E") splenic T cells when tested in primary mixed leukocyte reactions (MLR). After overnight (18-hr) incubation of the NPC, enrichment for transiently adherent, low-density (LD) cells on metrizamide gradients permitted the recovery of low numbers of cells (approx. 2-5 × 105 per liver), many of which displayed distinct DC morphology. Flow cytometric analysis revealed that these cells were CD3-, CD4-, CD8-, and B220-, but strongly expressed CD45 (leukocyte-common antigen), and mild-to-moderate levels of CD lib, heat-stable antigen, and CD44. The cells also expressed moderate intensity of NLDC 145 but not 33D1, DC restricted markers which have been shown to be differentially expressed on mouse DC isolated from various organs. This DC-enriched population was more strongly MHC class II(I-Ek)+ than NPC, as determined by immunocytochemistry and flow cytometry and exhibited much more potent allo-stimulatory activity for naive T cells. These findings demonstrate that freshly isolated murine liver NPC, and perhaps their counterparts in situ, exhibit allo-stimulatory activity that is enhanced in the nonadherent, low-density (DC-enriched) fraction after overnight culture. They further suggest that the © 1994 by Williams and Wilkins

In vitro propagation and homing of liver-derived dendritic cell progenitors to lymphoid tissues of allogeneic recipients: Implications for the establishment and maintenance of donor cell chimerism following liver transplantation

Dendritic cell (DC) progenitors were propagated in liquid culture from nonparenchymal cells resident in normal mouse (B10.BR; H-2k, I-E+) liver in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The liver-derived DC progenitors were MHC class II-/dim and did not express counter receptors for CTLA-4, a structural homologue of the Т cell activation molecule CD28. Following subcutaneous or intravenous injection, these liver-derived cells migrated to Т cell-dependent areas of lymph nodes and spleen of unmodified, allogeneic (BIO; H-2b; I-E_) recipients, where they were identified 1-5 days, and 1 and 2 months after injection by their strong surface expression of donor MHC class II (I-Ek) and their dendritic morphology. Maximal numbers of liver-derived DC in the spleen were recorded 5 days after injection. Both clusters of strongly donor MHC class II+ cells— and (more rarely) dividing cells—could also be identified, suggesting cell replication in situ. Using the same techniques employed to generate DC progenitors from normal liver, GM-CSF-stimulated cells were propagated for 10 days from the bone marrow and spleen of nonimmunosuppressed mice sacrificed 14 days after orthotopic liver transplantation (B10;H-2b → C3H;H-2k). Immunocytochemical staining for recipient and donor MHC class II phenotype revealed the growth both of host cells with DC characteristics, and of cells expressing donor alloantigens (I-Ab). These results are consistent with the growth, in response to GM-CSF, of donor-derived DC from progenitors seeded from the liver allograft to recipient lymphoid tissue. The functional activity of the progenitors of chimeric DC and the possible role of these cells in the establishment and maintenance of donor-specific tolerance following liver transplantation remain to be determined. © 1995 by Williams and Wilkins

Quantum equivalence of sigma models related by non Abelian Duality Transformations

Coupling constant renormalization is investigated in 2 dimensional sigma models related by non Abelian duality transformations. In this respect it is shown that in the one loop order of perturbation theory the duals of a one parameter family of models, interpolating between the SU(2) principal model and the O(3) sigma model, exhibit the same behaviour as the original models. For the O(3) model also the two loop equivalence is investigated, and is found to be broken just like in the already known example of the principal model.Comment: As a result of the collaboration of new authors the previously overlooked gauge contribution is inserted into eq.(43) changing not so much the formulae as part of the conclusion: for the models considered non Abelian duality is OK in one loo

The influence of arrangement of subgroups on the group structure

Investigation of groups satisfying certain related to arrangement of subgroups conditions allows algebraists to introduce and describe many important classes of groups. Most of these conditions are based on the fundamental notion of normality and built with the help of this concept di erent subgroup chains (series). Some of important results obtained on this way we will discuss in the current surve