Disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium ...analyzed for production of a range of pro-inflammatory mediators.
This study was conducted to confirm that the human intervertebral disc is capable of responding to a pro-inflammatory stimulus and to identify the principal mediators involved in any response.
Degenerate human disc tissue has been shown to spontaneously secrete a number of pro-inflammatory mediators. The importance of these molecules in the pathophysiology of symptomatic disc degeneration is increasingly recognized. Human nucleus pulposus has been shown to synthesize increased amounts of interleukin (IL)-6, prostaglandin E2 (PGE2), and nitric oxide in response to stimulation with IL-1beta. Murine nucleus pulposus synthesizes increased amounts of IL-1beta, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor in response to lipopolysaccharide stimulation. Lipopolysaccharide is a potent inducer of tumor necrosis factor-alpha (TNF-alpha), which is thought to play an important role in the pathophysiology of sciatica. To date, human nucleus pulposus has not been shown to secrete TNF-alpha in response to a pro-inflammatory stimulus.
Human disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium subsequently analyzed for a range of pro-inflammatory mediators.
None of the specimens produced any TNF-alpha, IL-1beta, granulocyte-macrophage colony-stimulating factor, or leukotriene B4. Measurable quantities of IL-6, IL-8, PGE2, MCP-1, basic fibroblast growth factor, and trans forming growth factor-beta1 were produced by a number of specimens. Lipopolysaccharide significantly increased IL-6, IL-8, and PGE2 production in both control and degenerate disc tissue. Degenerate disc specimens responded more vigorously to lipopolysaccharide stimulation than scoliotic specimens.
We conclude that both scoliotic and degenerate human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by secreting increased amounts of IL-6, IL-8, and PGE2 but not TNF-alpha and that degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its scoliotic counterpart.
Apoptosis is a distinct mechanism by which eukaryotic cells die. Neutrophils (PMN) play a fundamental role in the systemic inflammatory response syndrome. Clearance of PMN during resolution of the ...acute inflammatory process occurs by apoptosis, but factors inducing this process are unknown. The aims of this study were to determine whether PMN ingestion of Escherichia coli would result in PMN apoptosis and whether the mechanism was related to the respiratory burst. PMN from 10 healthy volunteers were cultured with different ratios of PMN:E. coli (1:0 to 1:25) for 12 h. Apoptosis was then assessed by propidium iodide DNA staining, morphology, gel electrophoresis, and Fc gamma RIII expression. There was a significant induction of PMN apoptosis on incubation with E. coli at a ratio of 1:10 and 1:25 PMN:E. coli as well as decreases in Fc gamma RIII. This correlated with increased ingestion of FITC-labeled E. coli and intracellular reactive oxygen intermediates after a 2-h coculture. To clarify the role of reactive oxygen intermediates in E. coli-induced PMN apoptosis, we assessed the effects of the antioxidants catalase, DMSO, glutathione, and N-acetylcysteine. There was a significant decrease in E. coli-induced PMN apoptosis on incubation with DMSO (1.0%), glutathione (25 mM), and N-acetylcysteine (25 mM) compared with control PMN:E. coli. This study demonstrates for the first time that E. coli induces PMN apoptosis through an oxygen-dependent mechanism. The removal of effete PMN by the process of apoptosis rather than necrosis may be teleologically beneficial during Gram-negative septicemia.
Detection of shielded nuclear material in a cargo container Jones, James L.; Norman, Daren R.; Haskell, Kevin J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
06/2006, Volume:
562, Issue:
2
Journal Article, Conference Proceeding
Peer reviewed
Open access
The Idaho National Laboratory, along with Los Alamos National Laboratory and the Idaho State University's Idaho Accelerator Center, are developing electron accelerator-based, photonuclear inspection ...technologies for the detection of shielded nuclear material within air-, rail-, and especially, maritime-cargo transportation containers. This paper describes a developing prototypical cargo container inspection system utilizing the Pulsed Photonuclear Assessment (PPA) technology, incorporates interchangeable, well-defined, contraband shielding structures (i.e., “calibration” pallets) providing realistic detection data for induced radiation signatures from smuggled nuclear material, and provides various shielded nuclear material detection results. Using a 4.8-kg quantity of depleted uranium, neutron and gamma-ray detection responses are presented for well-defined shielded and unshielded configurations evaluated in a selected cargo container inspection configuration.
Termination of a neutrophil-mediated inflammatory response occurs through the activation of the endogenous cell death program, apoptosis. Neutrophil apoptosis is a constitutive process that can be ...accelerated or delayed by signals from the microenvironment. Since cellular localization at the site of an inflammatory challenge is the critical first step in a neutrophil response, we investigated the effects of neutrophil transendothelial transmigration on the kinetic expression of apoptosis. Neutrophils isolated from rat lung following challenge with LPS demonstrated a significant delay in spontaneous apoptosis. This delay was a consequence of transmigration, since a comparable delay was seen when TNF-alpha, a potent inducer of apoptosis in vitro, was used as the inflammatory stimulus. Human neutrophils demonstrated comparable delays in apoptosis in vitro following migration across an endothelial monolayer in response to FMLP. Delayed apoptosis only occurred in cells that had first been primed by LPS, a stimulus shown to up-regulate beta2 integrins and down-regulate L-selectin. Finally, crosslinking of CD11a or CD11b, but not of CD18, with mAbs and F(ab')2 fragments produced a delay in spontaneous apoptosis, whereas crosslinking of L-selectin with mAb or its natural ligand, sulfatides, accelerated the apoptotic process. Cells in which apoptosis was inhibited demonstrated persistent functional respiratory burst activity. These observations establish a role for endothelial transmigration in the regulation of neutrophil apoptosis, and suggest that adhesion molecules serve a modulatory role in the expression of neutrophil programmed cell death.
We studied the effect of labor on maternal neutrophil phenotype.
Neutrophil apoptosis with inflammatory cytokines and the expression of CD11b, CD34 and toll-like receptor 4 (TLR4) were assessed with ...flow cytometry in women at uncomplicated vaginal delivery (VD), and elective cesarean section (ElCS) without labor, emergency cesarean section with (EmCSL+) or without (EmCSL−) labor.
Spontaneous neutrophil apoptosis is delayed in maternal neutrophils after VD, EmCSL+ or EmCSL− versus ElCS. In all groups lipopolysaccharide delayed apoptosis and increased CD11b expression. Elevated TLR4 expression in ElCS was associated with lipopolysaccharide responsiveness. CD34 was diminished in VD, indicating increased cell maturity.
Normal labor primes the neutrophil and may enhance antibacterial function by inducing a mild maternal inflammatory response syndrome. Delayed neutrophil apoptosis may promote the neutrophilia seen in women after VD. We suggest that labor of any duration may be immunologically beneficial to the parturient.
Eight patients with Parkinson's disease and eight matched controls were tested for concurrent task performance to examine whether Parkinson's disease produces deficits in the coordinating and ...integrating function of the central executive component of Baddeley's working memory model. Consistent with this prediction, the patients showed a significant decline in performance on a random pursuit tracking task while recalling digit span forward sequences, whereas the controls showed no such change. Performance on the component pursuit and digit span tasks, which did not differ between groups, was equated across subjects by varying the size of a target square and by using individual subjects' digit spans. The patient group also produced poorer word fluency scores and reported higher levels of depression, but there was no significant impairment on the Wisconsin card sort test. There was no association between dual task performance and any psychometric measure, target size, or disease related variables. Baddeley's working memory model is advantageous in providing a rich conceptual basis to explore and characterise cognitive abilities in patients with Parkinson's disease.
This study assessed the extent to which community-dwelling rural older adults mismanage their prescription medication regimens and predicted mismanagement of medications from selected socioeconomic, ...health status, and medication profile characteristics.
Personal interviews with 499 community-dwelling adults aged 66 and over taking at least one prescription medication and living in a rural region of the Southeast. With approximately equal numbers of African American and white men and women, the SUDAAN multiple logistic regression procedure was used to predict the mismanagement of prescription medications.
The mismanagement of prescribed medication regimens is relatively common among older adults. Those more likely than others to mismanage their regimens are African American, younger, in poorer mental health, with more acute care physician visits, and those who find payment for their medications to be problematic.
The implications of the findings for what is known about the self-modification of drug regimens, targeting prescription drug cost benefits or interventions, and the limitations of the study are discussed.
Postsplenectomy bacterial sepsis may be fatal, due to defects in both cellular and humoral immune responses. The objective of this study was to assess the efficacy of peritoneal macrophage ...antibacterial function in the early postsplenectomy period. Murine models of splenectomy and sham operation were characterized and peritoneal macrophages were harvested 24 h to 1 wk after surgery. Cells from splenectomized animals demonstrated a nonsignificant delay in phagocytosis of Escherichia coli at 24 h with, however, significantly impaired killing of intracellular organisms at 24 h and 1 wk compared to the sham group. Paradoxically, the production of the macrophage antibacterial product superoxide anion was not impaired at either time point in the splenectomy group compared with sham-operated and control mice. Nitric oxide release was significantly lower in the splenectomized group (p = 0.006), a possible explanation for reduced bacterial killing. Mortality from bacterial peritonitis was significantly higher with concomitant splenectomy than in the sham splenectomy group at 24 h (p < 0.02). The production of TNF from macrophages was up-regulated immediately following splenectomy, a cytokine which may contribute to mortality from bacteremic shock. Local defects in macrophage antimicrobial function may contribute significantly to bacteremia and to subsequent mortality in the early postsplenectomy period.
A study involving normal subjects and subjects with Parkinson's disease was undertaken to investigate the possibility that two-dimensional tasks provide more sensitive measures as well as additional ...information on sensory motor function than their 1-D counterparts. The performance of subjects with Parkinson's disease deteriorated more than their normal counterparts on going from a 1-D to 2-D random task. The 2-D tasks detected and quantified deficits in tracking ability in Parkinsonian subjects with greater sensitivity and these subjects were not impaired in their ability to make use of spatial predictability.
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