ISG15 is a 15-kDa protein of unique primary amino acid sequence, which is transcriptionally regulated by interferon (IFN) cx and IFN-f3. Because it is synthesized in many cell types and secreted from human monocytes and lymphocytes, we postulated that ISG15 might act to modulate immune cell function. ISG15 stimulated B-depleted lymphocyte proliferation in a dose-dependent manner with significant proliferation induced by amounts of ISG15 as low as 1 ng/ml (58 pM Although molecular mechanisms underlying biological responses to interferons (IFNs) are only partially dissected, it is thought that they are mediated by the regulated synthesis of induced proteins (1, 2). One of these IFN-induced gene products is ISG15 (3,4). ISG15 is a 15-kDa protein that is transcriptionally regulated by IFN-a or B (5,6). ISG15 is synthesized in mammalian cells as a 17-kDa precursor (pre-ISG15) that is processed by a cellular converting enzyme, cleaving the 8 carboxyl-terminal aa to yield the 157-aa mature ISG15 (4, 7), which is secreted from monocytes and lymphocytes (8). Both native and recombinant ISG15 induce the synthesis and secretion of IFN-'y from B-depleted lymphocytes (9).Based on its cytokine-like properties, it was hypothesized that ISG15 modulates immune effector cell activation and function. To evaluate this, effects on peripheral blood lymphocytes were assessed by [3Hlthymidine incorporation, immunophenotyping, and cytolytic assays. We demonstrate that ISG15 induced production of IFN-,y from T cells, augmented the proliferation of natural killer (NK) cells, and inducedThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.non-major histocompatibility complex-restricted cytolysis of tumor cell targets by NK-derived lymphokine-activated killer (LAK) cells in the absence of detectable levels of interleukin (IL) 2 or IL-12.MATERIALS AND METHODS Materials. B-depleted peripheral blood lymphocytes (PBLs) were purified by passage over a nylon wool column (9). By flow cytometry, this population was 80-85% CD3+, 5-8% CD16+, <2% CD14+, and <2% CD19+. Human recombinant IL-2 (2 x 107 units/mg) was from Hoffmann-LaRoche. Human recombinant IFN-y (2 x 107 units/mg) was from Biogen. A polyclonal antiserum to homogenous ISG15, purified from cytoplasms of IFN-,B-treated Daudi cells, was raised in a New Zealand White rabbit (7). Antigenic specificities of monoclonal antibodies used for flow cytometry included CD3 (Leu 4), CD14 (Leu M3), CD16 (Leu lla), CD19 (Leu 12), and CD56 (NKH-1) (Becton Dickinson).Expression and Purification of ISG15 and pre-ISG15. Human 157-aa ISG15 and the 165-aa pre-ISG15 were expressed and purified from Escherichia coli BL21(DE3) (10, 11). Endotoxin levels were <0.03 endotoxin units (EU)/,tg as measured by limulus amoebocyte lysate assay (sensitivity, 0.01 EU/ml). Heat-denatured ISG15 was ISG15 boiled for 20 min.Functional Assays. Proliferation ([3H]thy...

Airway complications remain a major cause of morbidity and mortality after cardiothoracic transplantation. The reported incidence of airway ischemic complications varies widely, contributed to by the lack of a universally accepted grading system and standardized definitions. Furthermore, the majority of the existing classification systems fail to integrate the wide range of possible bronchial complications that may develop after lung transplant. Hence, a Working Group was created by the International Society for Heart and Lung Transplantation with the aim of elaborating a universal definition of adult and pediatric airway complications and grading system. One such area of focus is to understand the problem in the context of a more standardized consensus of classifying airway ischemia. This consensus definition will have major clinical, therapeutics, and research implications.

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Background The short term superiority of video-assisted thoracoscopic surgery (VATS) lobectomy compared to open lobectomy for early stage lung cancer has been suggested by single institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared to open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. Methods 519 patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, gender, performance status, comorbidities, histology, tumor stage and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemar’s test for binary and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. P-values < 0.05 were considered significant. Results The matched data on length of hospital stay, complications and discharge dispositions significantly favored the VATS group. There was no statistically significant difference in survival between the two approaches. Conclusion This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer peri-operative complications and greater likelihood of independent home discharge compared to open lobectomy for early stage lung cancer. Survival was comparable between the two groups.

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