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Biomedical subjects

H Xu

Publications and source records attributed to H Xu.

834 records · Page 47Linked to original sources

Host defense mechanisms in polyaromatic hydrocarbon carcinogenesis.

Polyaromatic hydrocarbons (PAHs) are chemicals that are widely employed to examine the complex mechanisms by which chemicals cause cancer. While it is clear that the tumors that carcinogenic PAHs produce elicit an immune response, the interplay between host immune defense mechanisms and earlier stages in the cutaneous carcinogenesis pathway has received little attention. Studies from our laboratories have shown that topical application of several different PAHs to mice results in the development of an antigen-specific cell-mediated immune response to them. The response is genetically determined and is mediated by CD8+ T cells. Development of a cell-mediated immune response is associated with resistance to dimethylbenz(a)anthracene tumorigenesis. These findings are consistent with the hypothesis that host defense mechanisms against PAHs help to protect individuals from the carcinogenic actions of these agents. This may form the basis for novel immunopreventive strategies for individuals at high risk for development of tumors produced by PAHs.

Animals↗

Mitomycin C reduces haze formation in rabbits after excimer laser photorefractive keratectomy.

PURPOSE: To investigate the effects of mitomycin C on haze after photorefractive keratectomy (PRK). METHODS: Twenty of 24 rabbits underwent bilateral 193-nm excimer laser PRK to correct -10.00 D of myopia; the remaining four rabbits were not operated (no PRK group). The right eyes of the 20 rabbits were treated with 0.02% mitomycin C during surgery (PRK+MMC group) and the left eyes did not receive 0.02% mitomycin C (PRK alone group). Clinical and histopathologic examinations were performed. RESULTS: The most severe haze in the PRK alone group after PRK reached grade 3; the PRK+MMC group did not exceed grade 1 haze. Statistically significant differences were found between the PRK+MMC and PRK alone groups from week 2 to week 26 after treatment (P<.01). Epithelial thickening appeared for 26 weeks in both PRK groups; no statistically significant differences were found between the two PRK groups (P>.05). A marked reduction of keratocytes in the anterior stroma of the PRK+MMC group was observed. At week 1, 2, and 4 after PRK, keratocytes of the PRK+MMC group were only 3.1+/-2.6, 6.8+/-4.7, and 12.4+/-5.7 keratocytes x 10(4)/microm2, respectively, while those of the PRK alone group were 41.2+/-80, 42.3+/-7.8, and 40.0+/-3.3 keratocytes x 10(4)/microm2, respectively. There were statistically significant differences between the two groups (P<.001). CONCLUSION: A single intraoperative application of topical mitomycin C during PRK in rabbits reduced corneal haze by inhibiting the proliferation of keratocytes.

Administration, Topical↗

Photochemotherapy in human heart transplant recipients at high risk for fatal rejection.

Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk.

Adult↗

Natural antipig xenoantibody is absent in neonatal human serum.

BACKGROUND: Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the current shortage of donor organs suitable for heart allotransplantation. Unfortunately, discordant xenotransplantation is still limited by hyperacute rejection, a process thought to be mediated by natural antixenodonor antibodies. On the basis of our previous findings that cytotoxic natural xenoantibodies are immunoglobulin M in nature and that natural immunoglobulin M xenoantibodies are barely detectable in neonatal baboon serum, we postulated that immunoglobulin M xenoantibodies may be absent from newborn human serum. METHODS: Neonatal human sera were obtained from the cord blood of normal term infants and pooled. Pooled adult human sera were used as a control. A whole cell enzyme-linked immunosorbent assay and a complement-mediated cytotoxicity assay were performed to determine the binding and cytotoxicity of these xenoantibodies to pig aortic endothelial cells and pig lymphocytes. RESULTS: Neonatal human sera did not show binding of immunoglobulin M xenoantibodies to pig aortic endothelial cells or lymphocytes. However, low level binding of immunoglobulin G xenoantibodies was detected to pig endothelial cells and lymphocytes. In contrast, adult human sera showed significant binding of both natural immunoglobulin M and G xenoantibodies to pig aortic endothelial cells and lymphocytes. In addition, adult human immunoglobulin M xenoantibodies bound with similar avidity to both cultured adult and neonatal pig aortic endothelial cells. Although neonatal human sera were not cytotoxic to target cells, adult sera were cytotoxic to both pig aortic endothelial cells and pig lymphocytes. Our findings indicate that neonatal human sera lack natural antipig immunoglobulin M xenoantibodies, and therefore, neonatal human serum is not cytotoxic to pig endothelial cells or lymphocytes. Like adult pig endothelial cells, neonatal pig endothelial cells may also express similar membrane xenoantigens recognized by natural immunoglobulin M xenoantibodies. CONCLUSIONS: The absence of cytotoxic natural immunoglobulin M xenoantibodies in the neonate suggests that discordant xenotransplantation may be feasible in the neonate.

Adult↗