Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Limb girdle muscular dystrophy type 2B form and Miyoshi myopathy are both caused by mutations in the recently cloned gene dysferlin. In the present study, we have investigated whether cell transplantation could permit dysferlin expression in vivo. Two transplantation models were used: SCID mice transplanted with normal human myoblasts, and SJL mice, the mouse model for limb girdle muscular dystrophy type 2B and Miyoshi myopathy, transplanted with allogeneic primary mouse muscle cell cultures expressing the beta-galactosidase gene under control of a muscle promoter of Troponin I. FK506 immunosuppression was used in the non-compatible allogeneic model. One month after transplantation, human and mouse dysferlin proteins were detected in all transplanted SCID and SJL muscles, respectively. Co-localization of dysferlin and human dystrophin or beta-galactosidase-positive fibers was observed following the transplantation of myoblasts. Dysferlin proteins were monitored by immunocytochemistry and Western blot. The number of dysferlin-positive fibers was 40-50% and 20-30% in SCID and SJL muscle sections, respectively. Detection of dysferlin in both SCID mice and dysferlin-deficient SJL mouse shows that myoblast transplantation permits the expression of the donor dysferlin protein.
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PMID:Dysferlin expression after normal myoblast transplantation in SCID and in SJL mice. 1173 59

Nonhuman primates were used to define myoblast transplantation strategies applicable to humans. Nevertheless, previous experiments were based on the use of myotoxins concomitant with the myoblast injections. Since myotoxins must be avoided for clinical applications, we analyzed the efficacy of simple myoblast injections (i.e., myoblasts resuspended only in saline) into monkey muscles. We also evaluated different FK506 dosages (in combination or not with mycophenolate mofetil) for immunosuppression. Allogeneic myoblasts transduced with the beta-galactosidase (beta-Gal) gene were implanted in the muscles of 19 monkeys by injections placed 1 to 2 mm from each other. A biopsy was performed at the implanted sites 1 month later, and histologically studied for demonstration of beta-Gal+ myofibers, lymphocyte infiltration, and CD8+ cells. The presence of antibodies against the donor myoblasts and the blood levels of FK506 were analyzed. Our results show that: (1) If myoblast injections are sufficiently close to each other, high percentages of hybrid myofibers can be obtained following myoblast transplantation in primates (25 to 67% with an interinjection distance of 1 mm). (2) Efficient immunosuppression can be reached by increasing FK506 dosages, but also by combining this drug with mycophenolate mofetil, a combination that reduces toxic effects. The present results represent a step towards a better designing of myoblast transplantation strategies in humans.
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PMID:Efficacy of myoblast transplantation in nonhuman primates following simple intramuscular cell injections: toward defining strategies applicable to humans. 1200 64

Careful interpretation of tacrolimus levels is essential to ensure optimal immunosuppressive therapy while avoiding toxicity. Interference with tacrolimus assays may be an underreported event that has the potential to result in negative patient outcomes through unnecessary modifications of therapy. We describe a 55-year-old liver transplant recipient who had falsely elevated tacrolimus levels that led to the eventual disruption of his immunosuppressive therapy and subsequent rejection of his allograft.Although his increased tacrolimus levels did not correlate with clinical signs and symptoms of tacrolimus toxicity, interruption of therapy in this patient was supported by an acute infection and a slight elevation in serum creatinine concentration. Tacrolimus levels were analyzed by using an antibody conjugated magnetic immunoassay method, and levels as high as 79.7 ng/ml were observed, despite discontinuation of tacrolimus. We conducted an evaluation for assay interference by using an alternative assay method(microparticle enzyme immunoassay), by testing plasma samples that were not hemolyzed, and by analyzing levels of an unrelated drug that uses the same technology as the initial tacrolimus assay. beta-galactosidase antibodies were ultimately confirmed as the cause of the immunoassay interference. Inpatients receiving tacrolimus, spuriously high tacrolimus levels should be carefully evaluated, and drastic adjustments to therapy should be made only within the context of clinical toxicity.
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PMID:Falsely elevated tacrolimus levels caused by immunoassay interference secondary to beta-galactosidase antibodies in an infected liver transplant recipient. 2081 35


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