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Biomedical subjects

J Fung

Publications and source records attributed to J Fung.

229 records · Page 13Linked to original sources
PubMedDate not supplied

Constitutive and induced expression by pyridine and beta-naphthoflavone of rat CYP1A is sexually dimorphic.

Adult male and female Sprague-Dawley rats were compared in terms of the constitutive levels and inducibility of CYP1A1 and CYP1A2 (CYP1A) in lung, kidney, and liver. CYP1A were induced by i.p. treatment with pyridine (75 mg/kg per day) or beta-naphthoflavone (betaNF; 25 mg/kg per day) for two consecutive days and analyzed catalytically (via O-dealkylation of resorufin ethers), at the protein level (by Western blot analysis) and at the mRNA level (by Northern blot analysis). In untreated rats. CYP1A1 protein and its mRNA were detectable only in the lung and kidney of females but not males, whereas CYP1A2 protein and its mRNA were detectable only in the liver in either gender. Pyridine treatment upregulated CYP1A1 mRNA and its protein in the lung, kidney and liver in female rats, and upregulated the mRNA but not the protein in the lung and liver in male rats. Conversely, pyridine induced both CYP1A2 mRNA and protein in the liver in female rats, whereas it induced the protein but not its mRNA in the liver in male rats. No gender difference was observed in the plasma elimination rate of administered pyridine. BetaNF, in contrast to pyridine, induced CYP1A proteins, activities, and mRNA to higher levels in male than in female rats. The results show that the constitutive as well as inducible expression of CYP1A is sexually dimorphic in the Sprague-Dawley rat, with females being more responsive than males to induction by pyridine but with males being more responsive than females to induction by betaNF. The findings support the involvement of different mechanisms in CYP1A induction by pyridine and betaNF.

Animals↗
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Clinical trials and projected future of liver xenotransplantation.

The trial and error of the pioneering xenotransplant trials over the past three decades has defined the limitation of the species used. Success was tantalizingly close with the chimpanzee, baboon, and other primates. The use of more disparate species has been frustrated by the xenoantibody barrier. Future attempts at clinical xenotransplantation will be hampered by the consideration of the species of animals and the nature of the organs to be transplanted. On one hand, primate donors have the advantage of genetic similarity (and therefore potential compatibility) and less risk of immunologic loss. On the other hand, pig donors are more easily raised, are not sentient animals, and may be less likely to harbor transmissible disease. It is recognized that the success of xenotransplantation may very with different organs. Because it is relatively resistant to antibody-mediated rejection, the liver is the organ for which there is the greatest chance of long-term success. Consideration of using xenotransplants on a temporary basis, or as a "bridge" to permanent human transplantation, may allow clinical trials utilizing hearts or kidney xenografts. Issues on metabolic compatibility and infection risks cannot be accurately determined until routine success in clinical xenotransplantation occurs. Based on a limited experience, the conventional approaches to allotransplantation are unlikely to be successful in xenotransplantation. The avoidance of immediate xenograft destruction by hyperacute rejection, achieved using transgenic animals bearing human complement regulatory proteins or modulating the antigenic target on the donor organ, is the first step to successful xenotransplantation. The ability to achieve tolerance by establishing a state of bone marrow chimerism is the key to overcoming the long-term immunologic insults and avoiding the necessarily high doses of nonspecific immunosuppression that would otherwise be required and associated with a high risk of infections complications. Xenotransplantation faces criticism that is strongly reminiscent of that leveled against human-to-human transplantation during the late 1960s and early 1970s. Yet with persistence, the field of human-to-human transplantation has proved highly successful. This success was the result of a stepwise increase in our understanding of the biology of rejection, improvements in drug management, and experience. It is possible that xenotransplantation may not be universally successful until further technologic advances occur; yet cautions exploration of xenotransplantation appears warranted to identify those areas that require further study.

Animals↗
PubMedDate not supplied

Neuropsychiatric side effects of FK506 vs. cyclosporine A. First-week postoperative findings.

The authors studied 31 liver transplant patients to compare neuropsychiatric side effects of a newer immunosuppressant, FK506, to cyclosporine A (CYA). Patients were randomly assigned to either FK506 or CYA. At the 1-week postoperative stage, cognitive status was assessed with the Mini-Mental State Exam, Trailmaking Tests (TMT) A and B, Delirium Rating Scale, and a neuropsychiatric symptom checklist. No statistically significant differences were found on any outcome variable between these two drugs, though scores on the TMTs were impaired as compared with published norms. The FK506 patients had moderately impaired TMT scores, whereas the CYA patients had only mild impairment. The patients demonstrate good cognitive recovery at 1 week post-transplantation, with only mild evidence of cognitive impairment.

Adult↗
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The future of transplantation: with particular reference to chimerism and xenotransplantation.

The assumption for the last third of a century that stem cell-driven hematolymphopoietic chimerism was irrelevant to successful conventional whole organ transplantation has prompted alternative inadequate explanations of organ allograft acceptance. This assumption clouded the biologic meaning of successful organ as well as bone marrow transplantation, and precluded the development of a cardinal principle that accommodated all facets of transplantation. Recognition of this error and the incorporation of the chimerism factor into a two-way paradigm have allowed previous enigmas of organ as well as bone marrow engraftment to be explained. No credible evidence has emerged to interdict this interactive concept. If the two-way paradigm is correct, it will allow the remarkable advances that have been made in basic immunology to be more meaningfully exploited for transplantation, including that of xenografts.

Animals↗
PubMedDate not supplied

Initial studies with FK506 in renal transplantation.

FK506 is a novel immunosuppressive agent which is approximately 100 times as potent as cyclosporine in vitro. In this initial trial, 65 renal transplant patients of high complexity received primary FK506 immunosuppression. Overall, graft and patient survival rates are 80% and 98.5%, respectively. A major advantage of FK506 is its potency with relatively few side effects, which has permitted elimination of steroids in 31 (60%) of these patients. Because of these encouraging results, a randomized trial comparing the therapeutic efficacy and toxicity of FK506 and cyclosporine is currently underway at our institution.

Follow-Up Studies↗