Studies assessing the role of Stat5 in the IL-2 proliferative signal have produced contradictory, and thus inconclusive, results. One factor confounding many of these studies is the ability of IL-2R to deliver redundant mitogenic signals from different cytoplasmic tyrosines on the IL-2R β-chain (IL-2Rβ). Therefore, to assess the role of Stat5 in mitogenic signaling independent of any redundant signals, all cytoplasmic tyrosines were deleted from IL-2Rβ except for Tyr510, the most potent Stat5-activating site. This deletion mutant retained the ability to induce Stat5 activation and proliferation in the T cell line CTLL-2 and the pro-B cell line BA/F3. A set of point mutations at or near Tyr510 that variably compromised Stat5 activation also compromised the proliferative signal and revealed a quantitative correlation between the magnitude of Stat5 activation and proliferation. Proliferative signaling by a receptor mutant with a weak Stat5 activating site could be rescued by overexpression of wt Stat5a or b. Additionally, the ability of this receptor mutant to induce c-myc, bcl-x, and bcl-2 was enhanced by overexpression of wt Stat5. By contrast, overexpression of a version of Stat5a lacking the C-terminal trans-activation domain inhibited the induction of these genes and cell proliferation. Thus, Stat5 is a critical component of the proliferative signal from Tyr510 of the IL-2R and regulates expression of both mitogenic and survival genes through its trans-activation domain.

The interleukin 2 receptor (IL-2R) generates proliferative signals in T lymphocytes by ligand-induced heterodimerization of two chains, IL-2R␤ and ␥ c , which associate with the tyrosine kinases Jak1 and Jak3, respectively. Genetic and molecular studies have demonstrated that Jak3 is essential for mitogenic signaling by the ␥ c chain; because it is also the only molecule known to associate with ␥ c , we speculated that Jak3 might be sufficient for signaling by this chain. Therefore, fusion proteins were constructed in which all or part of the cytoplasmic domain of ␥ c was replaced by Jak3. Signaling was evaluated in the IL-2-dependent T cell line CTLL-2 using chimeric IL-2R␤ and ␥ c chains that bind and are activated by the cytokine granulocyte-macrophage colony-stimulating factor. Chimeric

Prosthetic vascular graft infections portend grave consequences if not treated expediently. Despite the low incidence of infection, the potential for limb loss or death greatly magnifies this complication. The surgical management of prosthetic graft infections has evolved over the last 2 decades. With the myriad therapeutic options now available, an algorithm is necessary to provide the optimal surgical treatment of Samson groups 1 through 5 extracavitary infected vascular prostheses. An extensive review of the literature was undertaken to evaluate the most effective management schemes. The authors found that 3 factors--Samson classification, bacteriology, and patient vascular anatomy--are vital to the surgical strategy. These 3 criteria were examined, and an algorithm was developed based on successful clinical and experimental results. This review provides a step-by-step rationale for the surgical management of extracavitary prosthetic graft infections according to the most successful reported outcomes.

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