Xenotransplantation of mitochondrial electron transfer enzyme, Ndi1, in myocardial reperfusion injury.

A significant consequence of ischemia/reperfusion (I/R) is mitochondrial respiratory dysfunction, leading to energetic deficits and cellular toxicity from reactive oxygen species (ROS). Mammalian complex I, a NADH-quinone oxidoreductase enzyme, is a multiple subunit enzyme that oxidizes NADH and pumps protons across the inner membrane. Damage to complex I leads to superoxide production which further damages complex I as well as other proteins, lipids and mtDNA.

Use of a continuous glucose sensor in an extracorporeal life support circuit.

Background: Standard care for infants on extracorporeal life support (ECLS) relies on intermittent measurement of blood glucose (BG); however, this can lead to significant changes in BG that go unrecognized for several hours. The present study was designed to assess performance and clinical applicability of a subcutaneous glucose sensor technology modified for use as a blood-contacting sensor within the ECLS circuit.

Methods: Twelve children, aged 3 years or less, requiring ECLS support were studied.

Cardioprotection through autophagy: ready for clinical trial?

Interventions that reduce infarct size in animal models have largely failed to improve outcome in patients suffering acute myocardial infarction (MI), or 'heart attack'. Our group recently reported a reduction of infarct size by chloramphenicol treatment in a porcine in vivo model of acute MI, through a mechanism involving the induction of autophagy. Since 2005 several studies have implicated autophagy as a target for cardioprotection.

Improving CT prediction of treatment response in patients with metastatic colorectal carcinoma using statistical learning theory.

Background: Significant interest exists in establishing radiologic imaging as a valid biomarker for assessing the response of cancer to a variety of treatments. To address this problem, we have chosen to study patients with metastatic colorectal carcinoma to learn whether statistical learning theory can improve the performance of radiologists using CT in predicting patient treatment response to therapy compared with the more traditional RECIST (Response Evaluation Criteria in Solid Tumors) standard.

Results: Predictions of survival after 8 months in 38 patients with metastatic colorectal carcinoma using the Support Vector Machine (SVM) technique improved 30% when using additional information compared to WHO (World Health Organization) or RECIST measurements alone.

Mitochondrial turnover in the heart.

Mitochondrial quality control is increasingly recognized as an essential element in maintaining optimally functioning tissues. Mitochondrial quality control depends upon a balance between biogenesis and autophagic destruction. Mitochondrial dynamics (fusion and fission) allows for the redistribution of mitochondrial components.

Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury.

Background: Emerging evidence suggests that "adaptive" induction of autophagy (the cellular process responsible for the degradation and recycling of proteins and organelles) may confer a cardioprotective phenotype and represent a novel strategy to limit ischemia-reperfusion injury. Our aim was to test this paradigm in a clinically relevant, large animal model of acute myocardial infarction.

Methods And Results: Anesthetized pigs underwent 45 minutes of coronary artery occlusion and 3 hours of reperfusion.

Improving CT prediction of treatment response in patients with metastatic colorectal carcinoma using statistical learning.

To establish radiologic imaging as a valid biomarker for assessing the response of cancer to different treatments. We study patients with metastatic colorectal carcinoma to learn whether Statistical Learning Theory (SLT) improves the performance of radiologists using Computer Tomography (CT) in predicting patient treatment response to therapy compared with traditional Response Evaluation Criteria in Solid Tumours (RECIST) standard. Preliminary research demonstrated that SLT algorithms can address questions and criticisms associated with both RECIST and World Health Organization (WHO) scoring methods.

Autophagy: definition, molecular machinery, and potential role in myocardial ischemia-reperfusion injury.

Autophagy is the endogenous, tightly regulated cellular "housekeeping" process responsible for the degradation of damaged and dysfunctional cellular organelles and protein aggregates. There is a growing consensus that autophagy is upregulated in the setting of myocardial ischemia-reperfusion. Moreover, emerging data suggest that autophagy may serve as an adaptive process and confer increased resistance to ischemia-reperfusion injury.

Autophagy induced by ischemic preconditioning is essential for cardioprotection.

Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5 min regional ischemia alternating with 5 min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent autophagosomes in cryosections. We found a rapid and significant increase in the number of autophagosomes in the risk zone of the preconditioned hearts.

Quantitative methodology using CT for predicting survival in patients with metastatic colorectal carcinoma: a pilot study.

Objective: To develop a methodology which quantifies multiple changing lesion features resulting in an optimized computed tomography (CT) response score (CRS) for prediction of overall survival (OS) in response to treatment for metastatic colorectal carcinoma (MCRC).

Subjects And Methods: This Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective study evaluated multiple changing imaging findings and their correlation with OS with a new methodology comparing the baseline and first post-treatment CT scans in 38 MCRC patients on last-line chemotherapy (cetuximab and irinotecan). Tumor size/enhancement changes and interval development of new lesions were quantified with either Likert-type scales (all parameters) or Response Evaluation Criteria in Solid Tumors (RECIST) (size change only).

Cyclophilin D is required for mitochondrial removal by autophagy in cardiac cells.

Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles. The mitochondrial permeability transition (MPT) results in mitochondrial depolarization and increased reactive oxygen species production, which can trigger autophagy. Therefore, we hypothesized that the MPT may have a role in signaling autophagy in cardiac cells.

Autophagy in health and disease. 5. Mitophagy as a way of life.

Our understanding of autophagy has expanded greatly in recent years, largely due to the identification of the many genes involved in the process and to the development of better methods to monitor the process, such as green fluorescent protein-LC3 to visualize autophagosomes in vivo. A number of groups have demonstrated a tight connection between autophagy and mitochondrial turnover. Mitochondrial quality control is the process whereby mitochondria undergo successive rounds of fusion and fission with a dynamic exchange of components to segregate functional and damaged elements.

Pim-1 kinase protects mitochondrial integrity in cardiomyocytes.

Rationale: Cardioprotective signaling mediates antiapoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector of AKT-mediated cardioprotection but the mechanistic basis for maintenance of mitochondrial integrity by Pim-1 remains unexplored. This study details antiapoptotic actions responsible for enhanced cell survival in cardiomyocytes with elevated Pim-1 activity.

Food access, availability, and affordability in 3 Los Angeles communities, Project CAFE, 2004-2006.

Introduction: Racial/ethnic minority communities are at increasingly high risk for chronic diseases related to obesity. Access to stores that sell affordable, nutritious food is a prerequisite for adopting a healthful diet. The objective of this study was to evaluate food access, availability, and affordability in 3 nonoverlapping but similar low-income communities in urban Los Angeles, California.

Autophagy during cardiac stress: joys and frustrations of autophagy.

The study of autophagy has been transformed by the cloning of most genes in the pathway and the introduction of GFP-LC3 as a reporter to allow visual assessment of autophagy. The field of cardiac biology is not alone in attempting to understand the implications of autophagy. The purpose of this review is to address some of the controversies and conundrums associated with the evolving studies of autophagy in the heart.

Juvenile exposure to anthracyclines impairs cardiac progenitor cell function and vascularization resulting in greater susceptibility to stress-induced myocardial injury in adult mice.

Background: The anthracycline doxorubicin is an effective chemotherapeutic agent used to treat pediatric cancers but is associated with cardiotoxicity that can manifest many years after the initial exposure. To date, very little is known about the mechanism of this late-onset cardiotoxicity.

Methods And Results: To understand this problem, we developed a pediatric model of late-onset doxorubicin-induced cardiotoxicity in which juvenile mice were exposed to doxorubicin, using a cumulative dose that did not induce acute cardiotoxicity.

Bnip3 mediates permeabilization of mitochondria and release of cytochrome c via a novel mechanism.

Bnip3 is a member of the BH3-only subfamily of pro-apoptotic Bcl-2 proteins and is associated with loss of cardiac myocytes after a myocardial infarction. Previous studies have demonstrated that Bnip3 induces mitochondrial dysfunction, but the mechanisms involved in this process remain unknown. In this study, we demonstrate that Bnip3 induces permeabilization of the mitochondria via a novel mechanism that is different from other BH3-only proteins.

Autophagy and protein kinase C are required for cardioprotection by sulfaphenazole.

Previously, we showed that sulfaphenazole (SUL), an antimicrobial agent that is a potent inhibitor of cytochrome P4502C9, is protective against ischemia-reperfusion (I/R) injury (Ref. 15). The mechanism, however, underlying this cardioprotection, is largely unknown.

The use of volumetric CT as an imaging biomarker in lung cancer.

Rationale And Objectives: Lung cancer is the leading cause of cancer death in the United States. Mortality outcomes have improved only modestly over the past 30 years. There is intense focus on the development of better treatments for lung cancer.

Extent of disease burden determined with magnetic resonance imaging of the bone marrow is predictive of survival outcome in patients with multiple myeloma.

Background: Multiple myeloma (MM) remains an incurable cancer. Treatment often is initiated at the time patients experience a progressive increase in tumor burden. The authors of this report investigated magnetic resonance imaging of the bone marrow (BM-MRI) as a novel approach to quantify disease burden and validated a staging system by correlating BM-MRI with common clinical and laboratory parameters.

Semiquantitative visual approach to scoring lung cancer treatment response using computed tomography: a pilot study.

Objective: Our objective was to compare a newly developed semiquantitative visual scoring (SVS) method with the current standard, the Response Evaluation Criteria in Solid Tumors (RECIST) method, in the categorization of treatment response and reader agreement for patients with metastatic lung cancer followed by computed tomography.

Materials And Methods: The 18 subjects (5 women and 13 men; mean age, 62.8 years) were from an institutional review board-approved phase 2 study that evaluated a second-line chemotherapy regimen for metastatic (stages III and IV) non-small cell lung cancer.