Advances in proteomic profiling of pediatric kidney diseases.

Chronic kidney disease (CKD) can progress to kidney failure and require dialysis or transplantation, while early diagnosis can alter the course of disease and lead to better outcomes in both pediatric and adult patients. Significant CKD comorbidities include the manifestation of cardiovascular disease, heart failure, coronary disease, and hypertension. The pathogenesis of chronic kidney diseases can present as subtle and especially difficult to distinguish between different glomerular pathologies.

Endogenous and iatrogenic sources of variability in response to opioid therapy in Post-Surgical and injured orthopedic patients.

Background: Hydrocodone is the most prescribed opioid in the US. The objective was to evaluate associations between genetic, intrinsic, and extrinsic patient factors, plasma hydrocodone and metabolites, common side effects, and pain scores in a cohort of orthopedic surgery patients.

Methods: Data for each patient was collected by review of the electronic hospital record (EHR), and patient interview.

Patients with Proliferative Lupus Nephritis Have Autoantibodies That React to Moesin and Demonstrate Increased Glomerular Moesin Expression.

Kidney involvement in systemic lupus erythematosus (SLE)-termed lupus nephritis (LN)-is a severe manifestation of SLE that can lead to end-stage kidney disease (ESKD). LN is characterized by immune complex deposition and inflammation in the glomerulus. We tested the hypothesis that autoantibodies targeting podocyte and glomerular cell proteins contribute to the development of immune complex formation in LN.

/ABIN1 and lupus nephritis: review.

SLE is a complex autoimmune disease with genetic, epigenetic, immune-regulatory, environmental and hormonal factors. Kidney inflammation and injury, termed lupus nephritis (LN), occurs in over half of patients with SLE and is a leading cause of disability and death. There is a high degree of short-term and long-term side effects associated with current LN therapies and they are not effective for many patients.

ELISA-based detection of Open Reading Frame protein 1 in patients at risk of developing lung cancer.

Background: Early detection of lung cancer significantly improves survival outcomes. Thus, lung cancer screening for high-risk individuals using low-dose CT scan (LDCT) is recommended. LDCT has several limitations, and often requires invasive follow up.

Does an antibiotic nail made in a lubricated tube release antibiotic?

Introduction: The treatment of long-bone osteomyelitis has long been a difficult problem. Recently, antibiotic-impregnated intramedullary rods for the treatment of infected long-bone fractures have been gaining popularity but they are quite difficult to fabricate. Recently, a new technique that utilizes mineral oil to coat the inside of a chest tube mold prior to introduction of cement has been proven to ease fabrication.

Long interspersed nuclear element-1 mobilization as a target in cancer diagnostics, prognostics and therapeutics.

Long Interspersed Nuclear Element-1 (LINE-1) are DNAs that compromise 17% of our genome. LINE-1 expression is triggered by environmental stressors and accomplished through its demethylation leading to genomic instability. Expression of LINE-1 is regulated in adult somatic tissues through several endogenous defensive mechanisms, but is found to be associated with tumorigenesis in several cancers.

Neutrophil exocytosis induces podocyte cytoskeletal reorganization and proteinuria in experimental glomerulonephritis.

Acute glomerulonephritis is characterized by rapid glomerular neutrophil recruitment, proteinuria, and glomerular hypercellularity. The current study tested the hypothesis that the release of neutrophil granule contents plays a role in both the loss of filtration barrier leading to proteinuria and the increase in glomerular cells. Inhibition of neutrophil exocytosis with a peptide inhibitor prevented proteinuria and attenuated podocyte and endothelial cell injury but had no effect on glomerular hypercellularity in an experimental acute glomerulonephritis model in mice.

Analytical interference of HBOC-201 (Hemopure, a synthetic hemoglobin-based oxygen carrier) on four common clinical chemistry platforms.

Background: There are 13 million blood transfusions each year in the US. Limitations in the donor pool, storage capabilities, mass casualties, access in remote locations and reactivity of donors all limit the availability of transfusable blood products to patients. HBOC-201 (Hemopure®) is a second-generation glutaraldehyde-polymer of bovine hemoglobin, which can serve as an "oxygen bridge" to maintain oxygen carrying capacity while transfusion products are unavailable.

ABIN1 Determines Severity of Glomerulonephritis via Activation of Intrinsic Glomerular Inflammation.

Transcription factor NF-κB regulates expression of numerous genes that control inflammation and is activated in glomerular cells in glomerulonephritis (GN). We previously identified genetic variants for a NF-κB regulatory, ubiquitin-binding protein ABIN1 as risk factors for GN in systemic autoimmunity. The goal was to define glomerular inflammatory events controlled by ABIN1 function in GN.

Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis.

Purpose: Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN.

ABIN1 dysfunction as a genetic basis for lupus nephritis.

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans.

Contributions of mass spectrometry-based proteomics to defining cellular mechanisms and diagnostic markers for systemic lupus erythematosus.

Systematic lupus erythematosus (SLE) is a complex disease for which molecular diagnostics are limited and pathogenesis is not clearly understood. Important information is provided in this regard by identification and characterization of more specific molecular and cellular targets in SLE immune cells and target tissue and markers of early-onset and effective response to treatment of SLE complications. In recent years, advances in proteomic technologies and applications have facilitated such discoveries.

Elongin C is a mediator of Notch4 activity in human renal tubule cells.

Notch proteins (Notch 1-4) are a family of trans-membrane cell surface receptors that are converted into transcriptional regulators when activated by interactions with cell surface ligands on adjacent cells. Ligand-binding stimulates proteolytic cleavage of the trans-membrane domain, releasing an active intracellular domain (ICD) that translocates to the nucleus and impacts transcription. In transit, the ICD may interact with regulatory proteins that modulate the expression and transcriptional activity.