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131.
Schnickel GT Bastani S Hsieh GR Shefizadeh A Bhatia R Fishbein MC Belperio J Ardehali A 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(7):4714-4721
Chemokine-chemokine receptor interactions orchestrate mononuclear cells recruitment to the allograft, leading to acute and chronic rejection. Despite biologic redundancy, several experimental studies have demonstrated the importance of CXCR3 and CCR5 in acute rejection of allografts. In these studies, deficiency or blockade of CXCR3 or CCR5 led to prolongation of allograft survival, yet allografts were ultimately lost to acute rejection. Given the above findings and the specificity of mononuclear cells bearing CXCR3 and CCR5, we hypothesized that combined blockade of CXCR3 and CCR5 will lead to indefinite (>100 days) graft survival in a full MHC-mismatched murine cardiac allograft model. The donor hearts in the control group were rejected in 6 +/- 1 days after transplantation. Combined blockade of CXCR3 and CCR5 prolonged allograft survival >15-fold vs the control group; all allografts survived for >100 days. More importantly, the donor hearts did not display any intimal lesions characteristic of chronic rejection. Further analysis of the donor hearts in the CXCR3/CCR5 blockade group demonstrated graft infiltration with CD4(+)CD25(+) T cells expressing the Foxp3 gene. Depletion of CD25(+) cells in the combined CXCR3 and CCR5 blockade group resulted in acute rejection of the allografts in 22 +/- 2 days. Combined CXCR3 and CCR5 blockade also reduced alloantigen-specific T lymphocyte proliferation. Combined CXCR3 and CCR5 blockade is effective in preventing acute and chronic rejection in a robust murine model. This effect is mediated, in part, by CD25(+) regulatory T cell recruitment and control of T lymphocyte proliferation. 相似文献
132.
133.
Keane MP Donnelly SC Belperio JA Goodman RB Dy M Burdick MD Fishbein MC Strieter RM 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(11):6515-6521
Diffuse alveolar damage is the histopathological hallmark of acute respiratory distress syndrome (ARDS) and is a stereotypic response to a variety of etiologies. Moreover, a significant proportion of ARDS survivors have residual pulmonary fibrosis and compromised pulmonary function. This suggests that the pathogenesis of diffuse alveolar damage that ultimately leads to the chronic fibrosis of ARDS has features of dysregulated repair exemplified by exaggerated intra-alveolar angiogenesis and fibrogenesis (i.e., fibroproliferation and deposition of extracellular matrix), leading to progressive alveolar fibrosis and impaired lung function. We obtained bronchoalveolar lavage fluid (BALF) from patients with ARDS or ventilated control patients and assessed CXC chemokine levels by ELISA. We found an imbalance in the expression of ELR(+) as compared with ELR(-) CXC chemokines from BALF of patients with ARDS as compared with controls. This imbalance correlated with angiogenic activity as assessed by the corneal micropocket assay. Furthermore, these levels correlated with both procollagen I and procollagen III levels in BALF. In contrast, while BALF levels of vascular endothelial growth factor were elevated, vascular endothelial growth factor did not appear to be significantly contributing to the angiogenic activity. These findings suggest that CXC chemokines have an important role in the fibroproliferative phase of ARDS via the regulation of angiogenesis. 相似文献
134.
ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation 总被引:14,自引:0,他引:14
Kennedy MA Barrera GC Nakamura K Baldán A Tarr P Fishbein MC Frank J Francone OL Edwards PA 《Cell metabolism》2005,1(2):121-131
Here we demonstrate that the ABC transporter ABCG1 plays a critical role in lipid homeostasis by controlling both tissue lipid levels and the efflux of cellular cholesterol to HDL. Targeted disruption of Abcg1 in mice has no effect on plasma lipids but results in massive accumulation of both neutral lipids and phospholipids in hepatocytes and in macrophages within multiple tissues following administration of a high-fat and -cholesterol diet. In contrast, overexpression of human ABCG1 protects murine tissues from dietary fat-induced lipid accumulation. Finally, we show that cholesterol efflux to HDL specifically requires ABCG1, whereas efflux to apoA1 requires ABCA1. These studies identify Abcg1 as a key gene involved in both cholesterol efflux to HDL and in tissue lipid homeostasis. 相似文献
135.
Presence and localization of three lactic acid transporters (MCT1, -2, and -4) in separated human granulocytes, lymphocytes, and monocytes. 总被引:2,自引:0,他引:2
136.
Cloning, expression, purification, and characterization of the acid alpha-mannosidase from Trypanosoma cruzi 总被引:1,自引:0,他引:1
Vandersall-Nairn AS; Merkle RK; O'Brien K; Oeltmann TN; Moremen KW 《Glycobiology》1998,8(12):1183-1194
The acid alpha-mannosidase of Trypanosoma cruzi is a broad-specificity
hydrolase involved in the catabolism of glycoconjugates, presumably in the
digestive vacuole. We have cloned the alpha-mannosidase gene from a T.cruzi
epimastigote genomic library. The alpha-mannosidase gene was determined to
be single copy by Southern analysis, and similar sequences were not
detected in genomic digests of either Trypanosoma brucei or Leishmania
donovani. The coding region was subcloned into the Pichia pastoris
expression vector pPICZ, and alpha-mannosidase activity was detected in the
medium of induced cultures. The recombinant alpha- mannosidase demonstrated
a pH optimum, inhibition by swainsonine, Km, and substrate specificity
consistent with the characteristics of the alpha-mannosidase previously
purified from T.cruzi epimastigotes. The recombinant enzyme was purified
103-fold from the culture medium of Pichia pastoris and had a native
molecular mass of 359 kDa by gel filtration. A combination of SDS-PAGE,
deglycosylation with endo H, and NH2-terminal sequencing indicates that the
enzyme is originally synthesized as a homodimeric polypeptide that is
subsequently cleaved to form a heterotetramer composed of 57 and 46 kDa
subunits. A polyclonal antibody raised to the recombinant enzyme was shown
to immunoprecipitate the alpha-mannosidase from T.cruzi cell extracts and
will be used in future immunolocalization studies.
相似文献
137.
Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases. 相似文献
138.
139.
Myoadenylate deaminase deficiency: inherited and acquired forms 总被引:2,自引:0,他引:2
W N Fishbein 《Biochemical medicine》1985,33(2):158-169
Myoadenylate deaminase deficiency, the most common of the known enzyme deficits of muscle, appears to occur in two forms. The primary type seems to be inherited as a complete gene block in an autosomal recessive pattern. Although occasionally diagnosed in infancy, when muscle biopsy is performed on a hypotonic but normoreflexic child, the deficiency is usually not symptomatic until adult or middle age, when muscle cramping and exercise intolerance develop. The skeletal muscle isozyme is immunologically, and presumably genetically, unique, and these patients have normal levels of adenylate deaminase in their other cells and tissues. A presumptive diagnosis can usually be made by an ischemic forearm exercise test, which shows a negligible increase in blood ammonia, despite a normal rise in lactate. Despite the absence of more than 99% of normal adenylate deaminase activity, the muscle biopsy shows no anatomic pathology, and other enzymes are at normal levels. These patients do not suffer progressive disease, and should be reassured, and encouraged to maintain physical activity. The heterozygous state is probably asymptomatic, except, perhaps, on extreme exercise, but may be associated with an increased incidence of malignant hyperthermia susceptibility. Since the gene defect is not rare, it is not surprising that some cases of the deficiency will be coincidentally associated with other neuromuscular disease. However, there is also a secondary form of myoadenylate deaminase deficiency, consequent to muscle damage from other disease. In this form, the residual activity is higher (1-10% of normal), may present rare foci of positive stain in the section, and reacts normally with antibody to the muscle isozyme. Other muscle enzymes are also depleted, although not as severely, and the prognosis in such cases is dictated by the primary disease. Since the heterozygous state is common, these patients might have been carriers, whose adenylate deaminase levels have been lowered for the deficient category by the advent of other neuromuscular disease. 相似文献
140.