Identification of a Cytotoxic Form of Dimeric Interleukin-2 in Murine Tissues

Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include “traditional” IL-2 receptor-bearing cells such as lymphocytes, as well as those less well known for IL-2 receptor expression, such as epithelial and smooth muscle cells. The morphologic changes and rapid cell death induced by dimeric IL-2 imply that cell death is mediated by disruption of membrane permeability and subsequent necrosis. These findings suggest that IL-2 has a direct and unexpectedly broad influence on cellular homeostatic mechanisms in both immune and non-immune systems

Molecular medicine and concepts of disease: the ethical value of a conceptual analysis of emerging biomedical technologies

Although it is now generally acknowledged that new biomedical technologies often produce new definitions and sometimes even new concepts of disease, this observation is rarely used in research that anticipates potential ethical issues in emerging technologies. This article argues that it is useful to start with an analysis of implied concepts of disease when anticipating ethical issues of biomedical technologies. It shows, moreover, that it is possible to do so at an early stage, i.e. when a technology is only just emerging. The specific case analysed here is that of ‘molecular medicine’. This group of emerging technologies combines a ‘cascade model’ of disease processes with a ‘personal pattern’ model of bodily functioning. Whereas the ethical implications of the first are partly familiar from earlier—albeit controversial—forms of preventive and predictive medicine, those of the second are quite novel and potentially far-reaching

Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome

To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS)

ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina)

The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease. Ischemic heart disease is the single leading cause of death in the U.S. The most common manifestation of this disease is chronic stable angina. Recognizing the importance of the management of this common entity and the absence of national clinical practice guidelines in this area, the task force formed the current committee to develop guidelines for the management of patients with stable angina. Because this problem is frequently encountered in the practice of internal medicine, the task force invited the American College of Physicians-American Society of Internal Medicine (ACP-ASIM) to serve as a partner in this effort by naming four general internists to serve on the committee

Climate control of terrestrial carbon exchange across biomes and continents

Peer reviewe

Cytokine and Proteomic Profiles of Amniotic Fluid in Women With Asymptomatic Short Cervix in the Midtrimester

Objective: Cervical shortening in the second trimester has been linked with inflammation and infection in the amniotic fluid (AF). Our goal was to establish cytokine and proteomic profiles in amniotic fluid of women with an asymptomatic short cervix in the midtrimester. Study Design: During ultrasound at 16-27 weeks, asymptomatic singleton pregnancies with an incidental finding of a transvaginal cervical length \u3c15mm were identified and underwent amniocentesis. Amniotic fluid was analyzed for infectious agents, cytokines, and proteomics by mass spectroscopy. All women were treated with vaginal progesterone from diagnosis until 34 weeks gestation. Pregnancy outcome data was collected and compared with AF findings. Results: There were 25 women identified with an asymptomatic short cervix and underwent amniocentesis. AF fluid gram stain and cultures were negative for pathogens. Average gestational age (GA) at birth was 30.7 weeks (range 19.3-41.1). Average latency time between amniocentesis and delivery was 62 days (range 3-150). 27 cytokines were tested, and 18 were found in more than 10 samples. Cytokine and proteomic levels did not have statistically significant correlation to GA at or to latency period to delivery. Conclusion: In women who are incidentally found to have an asymptomatic short cervix in the midtrimester, AF cytokine and proteomic profiles do not correlate to GA at birth or latency to delivery

Cytokine and Proteomic Profiles of Amniotic Fluid in Women With Asymptomatic Short Cervix in the Midtrimester

Objective: Cervical shortening in the second trimester has been linked with inflammation and infection in the amniotic fluid (AF). Our goal was to establish cytokine and proteomic profiles in amniotic fluid of women with an asymptomatic short cervix in the midtrimester. Study Design: During ultrasound at 16-27 weeks, asymptomatic singleton pregnancies with an incidental finding of a transvaginal cervical length \u3c15mm were identified and underwent amniocentesis. Amniotic fluid was analyzed for infectious agents, cytokines, and proteomics by mass spectroscopy. All women were treated with vaginal progesterone from diagnosis until 34 weeks gestation. Pregnancy outcome data was collected and compared with AF findings. Results: There were 25 women identified with an asymptomatic short cervix and underwent amniocentesis. AF fluid gram stain and cultures were negative for pathogens. Average gestational age (GA) at birth was 30.7 weeks (range 19.3-41.1). Average latency time between amniocentesis and delivery was 62 days (range 3-150). 27 cytokines were tested, and 18 were found in more than 10 samples. Cytokine and proteomic levels did not have statistically significant correlation to GA at or to latency period to delivery. Conclusion: In women who are incidentally found to have an asymptomatic short cervix in the midtrimester, AF cytokine and proteomic profiles do not correlate to GA at birth or latency to delivery