Modulation of alloimmunity with class I MHC peptides: mechanisms of action.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G D Wu.
Explore the source record for details and available documents.
Renewed interest in the transplantation of isolated hepatocytes into the liver as a potential therapy for liver disease has stimulated the development of methods for the identification of donor cells within the recipient organ. We describe a method for cellular tagging and in vivo identification of intraportally transplanted hepatocytes using an intracellular fluorescent dye, 5(6)-carboxyfluorescein diacetate, succinimidyl-ester (CFSE). Rat and porcine hepatocytes were isolated and labelled with CFSE. The optimal conditions for labelling consisted of a buffered saline suspension of hepatocytes (5 x 10(6) cells/mL) in 20.0 microM CFSE incubated for 15 min at 37 degrees C. In vitro, labelled hepatocytes were cultured either on fibronectin-coated chamber slides or in culture flasks. Cultures were evaluated in situ by fluorescence photomicrography or by fluorescence-activated cell sorting (FACS) after cell detachment. Cell viability was assessed serially and cultured, labelled hepatocytes retained the dye for up to 3 wk (last day of study). CFSE did not effect hepatocyte viability and there was no evidence of intercellular diffusion of the dye. In vivo, syngeneic Lewis rats underwent selective portal vein infusion of freshly isolated, labelled hepatocytes (2.0 x 10(7) cells/2.0 mL saline/animal) into the posterior liver lobes. All recipients were sacrificed 48 h and 96 h later and their livers examined. Transplanted hepatocytes were identified by fluorescence microscopy in tissue sections and by FACS following collagenase digestion of the liver tissue. CFSE persisted in a population of viable, engrafted hepatocytes. FACS analysis demonstrated that 9 +/- 3% of the hepatocytes in the posterior liver lobes were labelled 48 and 96 h after transplantation. At 96 h following transplantation, multiple engrafted hepatocytes could be observed by fluorescence microscopy around the central veins. CFSE labelling allows for both in vitro identification and in vivo localization of donor hepatocytes. Furthermore, it appears to be more stable and specific for labelling hepatocytes than other tested dyes (especially DiI).
Transplantation of vascularized organ allografts is associated with the development of arteriosclerosis in the vessels of the donor graft. We have recently examined the distribution of lymphocytic/mononuclear inflammatory cell subsets and histopathologic changes seen in the sequential development of transplant arteriosclerosis in cardiac allografts exchanged between inbred rat strain combinations (LEW-to-F344) that differ for weak histocompatibility loci. The donor grafts were harvested at 7, 14, 21, 28, 50 to 65, and 90 days after transplantation, and the vascular lesions were characterized for the immunopathologic changes associated with the chronic rejection of the grafts. The inflammatory cell infiltration of the graft myocardium was present as early as 7 days after transplantation (53.37 +/- 9.06 inflammatory cells/high-power field), and the accumulation of cells increased at 3 and 4 weeks after transplantation (112.12 +/- 16.58 and 130.40 +/- 21.24 cells/high-power field, respectively). The infiltrating inflammatory cells in the grafts at 4 weeks after transplantation were predominantly ED-1+ macrophages (63.39%), with a substantial number of OX19+ T lymphocytes (28%), OX8+ Tc/s cells (25.4%), 3.2.3+ natural killer cells (16.89%), W3/25+ Th cells (20.2%), and a small number of OX33+ B lymphocytes (1.13%) and interleukin-2 receptor+ T lymphocytes (2.6%). Among the T-cell population, most (87.6%) were positive (R73+) for T-cell receptors. The arteriosclerotic lesions present in the cardiac grafts exhibited a gradual increase in severity of the vascular intimal proliferation and a similar pattern of increased intensity of cellular infiltration. The lesions were infiltrated with inflammatory cells beginning in the first week and increasing for the first month after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
A quasi-historical cohort study method was used to collect the data of male stomach and liver cancer death from 1984 to 1988 in male residents (> or = 30 years old) of three tap-water-drinking communities at the upper, middle and lower reaches of the Huangpu River. Total person-years observed are 184,645. The result shows that the world standard population standardized cut-off mortalities (> or = 30 years old) of male stomach and liver cancer increase gradually from the upper to lower reaches. The mortalities from the upper to the lower reaches are 62.7, 86.2 and 146.0/100,000 person-years for male stomach cancer and 56.9, 67.7 and 81.3/100,000 person-years for male liver cancer, respectively. This trend is consistent with the change of the rate of positive Ames Test results of drinking water from the upper to lower reaches (0, 70, 100%). It suggests that a causal correlation may exist between the two. The distribution of other possible risk factors in the three communities is also described.
A quasi-historical cohort study method was used to collect the data of male stomach and liver cancer death and the data of exposure to relevant risk factors from 1984 to 1988 in male tap-water- and raw-water-drinking cohorts (> or = 30 years old) at both the upper and lower reaches of the Huangpu River. Total person-years observed are 172,448. The Odds Ratios of drinking water from the lower reaches for male stomach cancer and liver cancer death are 2.021 (p < 0.01) and 1.851 (p < 0.01), respectively, in unconditional logistic regression analysis after controlling possible confounding factors. The result shows that drinking water from the lower reaches of the Huangpu River is one of the important risk factors for male stomach and liver cancer death in local areas.