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- Byrne, J. A., et al.
(author)
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From intestine to muscle: Nuclear reprogramming through defective cloned embryos
- 2002
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99, s. 6059-6063
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Journal article (peer-reviewed)abstract
- Nuclear transplantation is one of the very few ways by which the genetic content and capacity for nuclear reprogramming can be assessed in individual cells of differentiated somatic tissues. No more than 6% of the cells of differentiated tissues have thus far been shown to have nuclei that can be reprogrammed to elicit the formation of unrelated cell types. In Amphibia, about 25% of such nuclear transfers form morphologically abnormal partial blastulae that die within 24 h. We have investigated the genetic content and capacity for reprogramming of those nuclei that generate partial blastulae, using as donors the intestinal epithelium cells of feeding Xenopus larvae. We have analyzed single nuclear transplant embryos obtained directly from intestinal tissue, thereby avoiding any genetic or epigenetic changes that might accumulate during cell culture. The expression of the intestine-specific gene intestinal fatty acid binding protein is extinguished by at least 104 times, within a few hours of nuclear transplantation. At the same time several genes that are normally expressed only in early embryos are very strongly activated in nuclear transplant embryos, but to an unregulated extent. Remarkably, cells from intestine-derived partial blastulae, when grafted to normal host embryos, contribute to several host tissues and participate in the normal 100-fold increase in axial muscle over several months. Thus, cells of defective cloned embryos unable to survive for more than 1 day can be reprogrammed to participate in new directions of differentiation and to maintain indefinite growth, despite the abnormal expression of early genes.
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- Ädelroth, E, et al.
(author)
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Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis
- 2000
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 106:2, s. 253-259
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Journal article (peer-reviewed)abstract
- Background: Allergic rhinitis is a common condition often requiring treatment. Objective: We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant humanized construct of a murine antibody that binds to circulating IgE, could control symptoms and reduce intake of concomitant medication in seasonal allergic rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule predicted to reduce serum free IgE levels below 25 ng/mL. Methods: We randomly assigned 251 adult subjects with a history of SAR and a positive skin test response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 times during the season, depending on baseline IgE levels. The primary efficacy variable was the subject's average daily nasal symptom severity score (sneezing, itching, runny, and stuffy nose) from diary data collected over the double-blind treatment period. Secondary efficacy variables included the average number of rescue antihistamine tablets per day, the proportion of days with any SAR medication use, and rhinoconjunctivitis-specific quality of life (QOL). Results: Significant between-treatment differences in favor of rhumAb-E25 were observed in average daily nasal symptom severity scores, the average number of tablets of rescue antihistamines per day, the proportion of days with any SAR medication use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb-E25-treated subjects and were associated with clinical effectiveness. Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were detected. Conclusion: Compared with placebo, rhumAb-E25 was safe and effective in controlling birch pollen-induced SAR symptoms, with less concomitant medication use and improved QOL. This study shows the therapeutic potential of anti-IgE antibody in SAR.
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