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EDITOR'S CHOICE 42(2)

Chang HS, Lin CH, Chen YC, Yu WC: Using siRNA technique to generate transgenic animals with spatiotemporal and conditional gene knockdown . Am J Pathol 165:1535–1541, 2004[Abstract/Free Full Text]

Successful long-term administration of exogenous therapeutic proteins such as erythropoietin can be both costly and challenging. A new gene therapy approach to this problem was recently described by a group of British researchers. These investigators created mice transgenic for the human erythropoietin under the control of an immunoglobulin promoter, then immunized the mice with phycoerythrin. Phycoerythrin-specific B cells were isolated and adoptively transferred to syngeneic animals. When stimulated with phycoerythrin, the transferred lymphocytes proliferated, produced human erythropoietin, and corrected anemia in the recipient mice. This demonstrates that memory lymphocytes, which are very long-lived and undergo clonal expansion when exposed to specific antigen, can secrete cloned proteins with biological activity. This may offer a new approach for therapeutic protein delivery.

Takacs K, Du Roure C, Nabarro S, Dillon N, McVey JH, Webster Z, Macneil A, Bartok I, Higgins C, Gray D, Merkenschlager M, Fisher AG: The regulated long-term delivery of therapeutic proteins by using antigen-specific B lymphocytes . Proc Natl Acad Sci U S A 101:16298–16303, 2004[Abstract/Free Full Text]

A consortium of over 100 international scientists recently completed the draft genome sequence of the red jungle fowl, Gallus gallus, the ancestor of the domestic chicken. The chicken genome is one-third the size of most mammalian genomes. The small size of the genome appears to be due to the paucity of retroposed pseudogenes, the absence of short interspersed nucleotide elements, and reduced large segmental duplications. The chicken has one pair of sex chromosomes and 38 autosomes. Autosomes include large macrochromosomes that resemble mammalian chromosomes and tiny microchromosomes not commonly found in mammals. Microchromosomes are GC-rich and contain few repetitive sequences. Comparison of the chicken and human genomes indicates that at least 70 megabases of shared sequence are likely to be functional in both species. These findings will provide information valuable for the fields of agriculture and comparative genomics.

International Chicken Genome Sequencing Consortium: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution . Nature 432:695–716, 2004[CrossRef][Medline]

Epithelial tumors commonly metastasize first to regional lymph nodes, suggesting that lymph nodes pose mechanical or biological barriers to tumor spread. To test this hypothesis, Japanese scientists injected fluorescently labeled syngeneic cancer cells into rat cecum submucosa. They monitored the appearance of these cells in the regional mesenteric lymph node and the response of the lymph node to the cells. Cancer cells were arrested in the marginal sinus of the node. Hyperplasia of lymphoid follicles and medullary lymphoid cells developed very soon after tumor cell arrival, and macrophages migrated into the marginal sinus, where they apparently engulfed apoptotic tumor cells. Depleting lymph nodes of macrophages significantly enhanced the growth of metastatic tumor cells. The cytokines tumor necrosis factor-, interleukin 1-ß, and interleukin 2 also increased in the lymph node after the tumor cells entered the lymph node, while interferon-, interleukin-4, and interleukin-12 decreased. These studies demonstrate that lymph nodes do serve, at least transiently, to filter metastatic cancer cells from the circulation.

Nagata H, Arai T, Soejima Y, Suzuki H, Ishii H, Hibi T: Limited capability of regional lymph nodes to eradicate metastatic cancer cells . Cancer Res 64:8239–8248, 2004[Abstract/Free Full Text]

Lambs derived by nuclear cloning often develop renal defects, including hydronephros consistent with urinary out-flow obstruction. Nephrogenesis occurs by the reciprocal induction of epithelial and mesenchymal elements. Many of the epithelial elements in the kidneys arise by the process of mesenchymal to epithelial transition. British investigators have now shown that this process is faulty in cloned lambs. By immunohistochemistry, they showed that, compared to normally developing kidneys, cytokeratin expression is increased in damaged tubules; desmin, vimentin, and smooth muscle actin are expressed in undifferentiated mesenchyme; and vimentin and desmin are re-expressed on proximal tubular epithelial cells in the kidneys of cloned lambs. The etiology of this dysregulated developmental process is not known.

Dawson AJ, King TJ, Wilmut I, Harkness LM, Kelly BG, Rhind SM: Immunohistochemical characterization of cloned lamb nephropathy . J Histochem Cytochem 52:1657–1664, 2004[Abstract/Free Full Text]

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                            What's this?