Posterolateral Lumbar Spinal Fusion with Autogenous Bone Chips from Laminectomy Extended with OsteoSet®

BackgroundThis study was conducted to evaluate posterolateral lumbar fusion with autogenous corticocancellous bone chips from the laminae and spinous processes extended with OsteoSet® instead of cancellous bone from the iliac crest.MethodsA total of 124 patients who underwent posterior decompression and posterolateral fusion with instrumentation between May 2001 and December 2003 were analyzed retrospectively. The study population comprised 49 males and 75 females with a mean age of 66 ± 9.5 years. In all the patients, corticocancellous bone chips from laminectomy and OsteoSet® were used as the graft material. There was no cancellous bone harvested from the iliac crest. The follow-up period was 28 + 7.1 months.ResultsThe overall union rate was 91%, and the average union time was 3.9 months. There were 3 complications, including 2 patients with dura tear, and 1 with deep infection. At the final follow-up, the good and excellent results were up to 83.9%.ConclusionGraft material from laminae and spinous processes extended with OsteoSet® is reliable and effective enough to replace the graft from the posterior iliac crest

Enteric bacterial loads are associated with interleukin-6 levels in systemic inflammatory response syndrome patients

AbstractBackgroundLoss of intestinal integrity is a critical contributor to excessive inflammation following severe trauma or major surgery. In the case of enterocyte damage, intestinal fatty acid-binding protein (IFABP) is released into the extracellular space. Excessive production of interleukin (IL)-6 can induce systemic inflammatory response syndrome (SIRS). However, the correlation of IL-6 with gut barrier failure and bacterial translocation in critically ill patients has not been well characterized.PurposesTo define the relationship between enteric bacterial loads and IL-6 levels in patients with SIRS.MethodsVariables related to prognosis and treatment were measured in 85 patients with SIRS upon admission to the emergency room. IL-6 and IFABP were measured using an enzyme-linked immunosorbent assay. Enteric bacterial loads in blood were measured through quantitative real-time polymerase chain reaction with primers specific for enteric bacteria.ResultsMultivariate analysis revealed a positive correlation between enteric bacterial loads and IL-6 levels in blood. Elevated IFABP concentration was associated with low blood pressure, high respiration rate, hyperglycemia, and high Sequential Organ Failure Assessment score. Elevated C-reactive protein concentrations were associated with higher soluble CD14 levels in blood.ConclusionEnterocyte damage is associated with hypotension and tachypnia in patients with SIRS. Gut function failure may permit enteric bacteria to enter the blood, thereby elevating IL-6 levels and inducing a systemic inflammatory response, resulting in multiple organ failure

Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials

Estrogen Augments Shear Stress–Induced Signaling and Gene Expression in Osteoblast-like Cells via Estrogen Receptor–Mediated Expression of β1-Integrin

Estrogen and mechanical forces are positive regulators for osteoblast proliferation and bone formation. We investigated the synergistic effect of estrogen and flow-induced shear stress on signal transduction and gene expression in human osetoblast-like MG63 cells and primary osteoblasts (HOBs) using activations of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) and expressions of c-fos and cyclooxygenase-2 (I) as readouts. Estrogen (17β-estradiol, 10 nM) and shear stress (12 dyn/cm2) alone induced transient phosphorylations of ERK and p38 MAPK in MG63 cells. Pretreating MG63 cells with 17β-estradiol for 6 hours before shearing augmented these shear-induced MAPK phosphorylations. Western blot and flow cytometric analyses showed that treating MG63 cells with 17β-estradiol for 6 hrs induced their β1-integrin expression. This estrogen-induction of β1-integrin was inhibited by pretreating the cells with a specific antagonist of estrogen receptor ICI 182,780. Both 17β-estradiol and shear stress alone induced c-fos and Cox-2 gene expressions in MG63 cells. Pretreating MG63 cells with 17β-estradiol for 6 hrs augmented the shear-induced c-fos and Cox-2 expressions. The augmented effects of 17β-estradiol on shear-induced MAPK phosphorylations and c-fos and Cox-2 expressions were inhibited by pretreating the cells with ICI 182,780 or transfecting the cells with β1-specific small interfering RNA. Similar results on the augmented effect of estrogen on shear-induced signaling and gene expression were obtained with HOBs. Our findings provide insights into the mechanism by which estrogen augments shear stress responsiveness of signal transduction and gene expression in bone cells via estrogen receptor–mediated increases in β1-integrin expression. © 2010 American Society for Bone and Mineral Research

Climate-mediated cooperation promotes niche expansion in burying beetles

The ability to form cooperative societies may explain why humans and social insects have come to dominate the earth. Here we examine the ecological consequences of cooperation by quantifying the fitness of cooperative (large groups) and non-cooperative (small groups) phenotypes in burying beetles (Nicrophorus nepalensis) along an elevational and temperature gradient. We experimentally created large and small groups along the gradient and manipulated interspecific competition with flies by heating carcasses. We show that cooperative groups performed as thermal generalists with similarly high breeding success at all temperatures and elevations, whereas non-cooperative groups performed as thermal specialists with higher breeding success only at intermediate temperatures and elevations. Studying the ecological consequences of cooperation may not only help us to understand why so many species of social insects have conquered the earth, but also to determine how climate change will affect the success of these and other social species, including our own

Dioscorea Phytocompounds Enhance Murine Splenocyte Proliferation Ex Vivo and Improve Regeneration of Bone Marrow Cells In Vivo

Specific cytokines have been tested clinically for immunotherapy of cancers; however, cytotoxicity has often impaired their usefulness. Consequently, alternative approaches are increasingly desirable. Dioscorea spp. tuber is a widely used traditional Chinese medicinal herb claimed to confer immunostimulatory activity. In this study, we evaluated Dioscorea as an adjuvant therapy for use alongside chemotherapy for cancer. Phytocompounds from Dioscorea tubers were ethanol fractioned and used for ex vivo splenocyte proliferation assay or in vivo force-feeding of mice pre-treated with the chemotherapy agent 5-fluorouracil. Co-treatment with a 50–75% ethanol-partitioned fraction of the tuber extract of D. batatas (DsCE-II) and interleukin (IL)-2 resulted in a significantly higher rate of murine splenocyte cell proliferation ex vivo than treatment with DsCE-II or IL-2 alone. This DsCE-II fraction, which contains a polysaccharide with a high proportion of β-1,4-linkage mannose (≥64%), also promoted the regeneration of specific progenitor cell populations in damaged bone marrow tissues of 5-fluorouracil-treated mice. Colony-forming unit (CFU) analyses demonstrated that the population of CFU-GM cells, but not CFU-GEMM or BFU-E cells, preferentially recovered to ~67% in the bone marrow of immune-suppressed mice fed with DsCE-II. DsCE-II efficacy level was ~85% of that obtained by subcutaneous administration of recombinant G-CSF proteins (5 μg kg−1) in mice tested in parallel. This study suggests that the DsCE-II fraction of D. batatas extract may be considered for further development as a dietary supplement for use alongside chemotherapy during cancer treatment

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts