[Long-term outcomes of urinary flow impairement on renal hemodynamics: from animal experiments to clinical research].
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Animals↗
Biomedical subjects
T Roger
Publications and source records attributed to T Roger.
A preliminary study of reliability of impedance measurement to detect iatrogenic initial pedicle perforation (in the porcine model).
Accidental perforation of the vertebral pedicle wall is a well-known complication associated with standard approach of pedicle screw insertion. Depending on detection criteria, more than 20% of screws are reported misplaced. Serious clinical consequences, from dysesthesia to paraplegia, although not common, may result from these misplaced screws. Many techniques have been described to address this issue such as somatosensory evoked potentials, electromyography, surgical navigation, etc. Each of these techniques presents advantages and drawbacks, none is simple and ergonomic. A new drilling tool was evaluated which allows for instant detection of pedicle perforation by emission of variable beeps. This new device is based on two original principles: the device is integrated in the drilling or screwing tool, the technology allows real-time detection of perforation through two independent parameters, impedance variation and evoked muscular contractions. A preliminary animal study was conducted to assess the safety and efficacy of this system based upon electrical conductivity. A total of 168 manual pedicle drillings followed by insertion of implants were performed in 11 young porcine lumbar and thoracic spines. The presence or absence of perforation detection, which defines the reliability of the device, was correlated with necropsic examination of the spines. Using this protocol the device demonstrated 100% positive predictive value, 96% negative predictive value, 100% specificity, and 97% sensitivity. Of 168 drillings there were three (1.79%) false-negatives, leading to a minor effraction, cranially in the intervertebral disks, nine (5.36%) screw threads breaching the vertebral cortex when inserting screws, although preparation of the holes did not indicate any perforation, 34 (36%) breaches detected by the instrument and not detected by the surgeon. These results confirm that the impedance variation detection capability of this device offers a simple and effective means to detect perforation in vertebral pedicle, prior to insertion of pedicle screws. Due to the porcine nerve root anatomy, it was not possible to evaluate the added benefit of cross-linking impedance and EMG detection. A future clinical study may further explore the subject of current study.
Animals↗
Tumour necrosis factor-alpha up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-kappaB.
BACKGROUND: A series of controlled changes including proliferation, secretion and menstrual shedding occur in the human endometrium during every normal menstrual cycle. Macrophage migration inhibitory factor (MIF), a multifunctional cytokine with numerous proinflammatory, immunomodulatory and angiogenic properties, appears to be expressed in the human endometrium and to follow a regulated cycle phase-dependent expression, but the mechanisms underlying endometrial MIF expression remain to be fully elucidated. METHODS AND RESULTS: Results from enzyme-linked immunosorbent assay (ELISA) demonstrated a significant dose- and time-dependent increase in MIF secretion by human endometrial cells in response to tumour necrosis factor-alpha (TNF-alpha) (0.1-100 ng/ml). This increase was also observed at the mRNA level as shown by reverse transcription (RT)-PCR. Curcumin (10(-8) mol/l), a known nuclear factor (NF)-kappaB inhibitor, inhibited the TNF-alpha-induced pIkappaB phosphorylation as shown by western blotting, NF-kappaB translocation into the nucleus as shown by electrophoretic mobility shift assay, and MIF synthesis and secretion as measured by ELISA and RT-PCR. The expression of a dominant-negative NF-kappaB inhibitor (IkappaB) significantly decreased the TNF-alpha-induced MIF promoter activity as analysed by transient cell transfection. CONCLUSIONS: These results indicate clearly that TNF-alpha up-regulates the expression of MIF in endometrial stromal cells. This took place possibly through NF-kappaB activation, and may play an important role in the physiology of the human endometrium.
Cells, Cultured↗
Macrophage migration inhibitory factor and innate immune responses to bacterial infections.
OBJECTIVES: To review the role of macrophage migration inhibitory factor (MIF) in host responses to infection and to explore the potential of MIF as a novel target for therapeutic intervention in patients with severe sepsis and septic shock. DATA SOURCES: Published articles on the role of MIF in innate immune responses against microbial pathogens. DATA SUMMARY: MIF has emerged recently as an important effector molecule of the innate immune system. MIF is expressed constitutively by monocytes/macrophages, T cells, B cells, endocrine cells, and epithelial cells. Microbial toxins and cytokines are powerful inducers of MIF release by immune cells. MIF expression is up-regulated during the course of inflammatory and infectious diseases and was found to play an important role in the pathogenesis of sepsis and septic shock. CONCLUSION: Given the role of MIF in innate immune responses against microbial pathogens and in the regulation of inflammatory responses, modulation of MIF production or neutralization of its activity may offer new therapeutic options for the management of patients with sepsis.
Animals↗
Macrophage migration inhibitory factor (MIF) modulates innate immune responses induced by endotoxin and Gram-negative bacteria.
Discovered in the early 1960s as a T-cell cytokine, MIF has emerged to be an important mediator of the innate immune system. MIF was identified recently to be released by a vast array of cells, including monocytes/macrophages, T-cells, B-cells, endocrine cells and epithelial cells in response to infection and stress. Bacteria, microbial toxins and cytokines have been shown to be powerful inducers of MIF secretion by macrophages. MIF stimulates the expression of pro-inflammatory mediators by immune cells and functions to counterbalance the anti-inflammatory and immunosuppressive effects of glucocorticoids. Like TNF and IL-1, MIF plays an important role in host responses to infection. Recombinant MIF was found to exacerbate lethal endotoxemia or bacterial sepsis when co-injected with LPS or Escherichia coli in mice. Conversely, MIF knockout mice or mice treated with anti-MIF antibodies were protected from shock induced by LPS, staphylococcal exotoxins or bacterial peritonitis, even when anti-MIF therapy was started after the onset of infection. Given the central role played by MIF in innate immune responses against microbial pathogens and in the regulation of inflammatory responses, pharmacological modulation of MIF production or neutralization of MIF activity could have broad clinical applications and may offer new treatment options for the management of patients with severe sepsis or septic shock.
Animals↗
Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1.
Cytokines are multifunctional mediators that classically modulate immune activity by receptor-mediated pathways. Macrophage migration inhibitory factor (MIF) is a cytokine that has a critical role in several inflammatory conditions but that also has endocrine and enzymatic functions. The molecular targets of MIF action have so far remained unclear. Here we show that MIF specifically interacts with an intracellular protein, Jab1, which is a coactivator of AP-1 transcription that also promotes degradation of the cyclin-dependent kinase inhibitor p27Kip1 (ref. 10). MIF colocalizes with Jab1 in the cytosol, and both endogenous and exogenously added MIF following endocytosis bind Jab1. MIF inhibits Jab1- and stimulus-enhanced AP-1 activity, but does not interfere with the induction of the transcription factor NFkappaB. Jab1 activates c-Jun amino-terminal kinase (JNK) activity and enhances endogenous phospho-c-Jun levels, and MIF inhibits these effects. MIF also antagonizes Jab1-dependent cell-cycle regulation by increasing p27Kip1 expression through stabilization of p27Kip1 protein. Consequently, Jab1-mediated rescue of fibroblasts from growth arrest is blocked by MIF. Amino acids 50-65 and Cys 60 of MIF are important for Jab1 binding and modulation. We conclude that MIF may act broadly to negatively regulate Jab1-controlled pathways and that the MIF-Jab1 interaction may provide a molecular basis for key activities of MIF.
COP9 Signalosome Complex↗
IL-6 protein production by airway epithelial(-like) cells disabled in IL-6 mRNA degradation.
IL-6 mRNA and protein expression in human airway epithelial-like H292 cells depends on rapid, but regulable IL-6 mRNA degradation. We restricted IL-6 mRNA degradation by partially inhibiting protein synthesis and studied the IL-6 response. Despite partial inhibition of protein synthesis, IL-6 protein production was increased and prolonged. Furthermore, the threshold concentration for stimuli of IL-6 protein production decreased and the dose-response curves became steeper. Similar findings were obtained with primary human bronchial epithelial cells. This exaggerated production may apply to other proteins encoded by labile mRNA and is likely to occur during viral infection of airway epithelial cells.
Cells, Cultured↗
Intracranial aneurysms: detection with gadolinium-enhanced dynamic three-dimensional MR angiography-initial results.
PURPOSE: To assess the clinical utility and accuracy of contrast material-enhanced dynamic three-dimensional (3D) T1-weighted magnetic resonance (MR) angiography in the detection of unruptured intracranial aneurysms. MATERIALS AND METHODS: A prospective blinded comparison of 3D contrast-enhanced T1-weighted MR angiography with 3D inflow magnetization transfer and tilted optimized nonsaturating excitation (MT TONE) imaging, phase-contrast MR angiography, and conventional digital subtraction angiography (DSA) was performed in 32 consecutive patients. The first dynamic 3D contrast-enhanced T1-weighted acquisition was individually timed after injection of a bolus of gadolinium-based contrast agent to obtain an arterial phase image followed by two sequential venous phase images (three 18-second acquisitions). Two readers independently interpreted and graded the MR images for diagnostic confidence and depiction of aneurysms and subsequently compared them with DSA images. RESULTS: Three-dimensional contrast-enhanced T1-weighted MR angiograms depicted all 23 aneurysms detected in 17 patients at DSA (mean size, 6 mm; range, 2-21 mm) with one false-positive result by one reader (sensitivity, 100%; specificity, 94%). MT TONE and phase-contrast images failed to depict one and seven aneurysms, respectively (MT TONE sensitivity of 96% and specificity of 100%, phase-contrast sensitivity of 70% and specificity of 100%). Aneurysm depiction at 3D contrast-enhanced T1-weighted MR angiography was significantly better than that at MT TONE imaging (P <.012), and that with both was significantly superior to that of phase-contrast imaging (P <. 001). Differences in diagnostic confidence in the presence of an aneurysm were not significant between 3D contrast-enhanced T1-weighted and MT TONE imaging (P =.076). CONCLUSION: Dynamic 3D contrast-enhanced T1-weighted MR angiography is a fast, efficient, and minimally invasive imaging method with which to diagnose intracranial aneurysms.
Adult↗
[Post-traumatic carotid-cavernous sinus fistula].
The authors report the case of a 51 year-old man who developed a carotid-cavernous sinus fistula after a blunt trauma. In view of an exophthalmia, an impressive chemosis, a pupillary dilatation due to parasympathetic paralysis and a bruit over the right orbit, a carotid-cavernous sinus fistula was diagnosed. The existence of the fistula was confirmed by a brain CT scan and a cerebral angiogram. Carotid-cavernous sinus fistulas are rare. They are spontaneous or posttraumatic. Cerebral angiography is the diagnostic procedure of choice. The authors review the signs and symptoms, diagnostic procedures, treatment, and prognosis of this complication.
Arteriovenous Fistula↗
Superinduction of interleukin-6 mRNA in lung epithelial H292 cells depends on transiently increased C/EBP activity and durable increased mRNA stability.
Restriction of eukaryotic protein synthesis affects the regulation of some transiently expressed gene transcripts resulting in their superinduction. We determined the transcriptional and post-transcriptional processes implicated in IL-6 mRNA superinduction in a human lung-derived epithelial cell line H292, and their kinetics in the absence and presence of an exogenous stimulus, tumor necrosis factor-alpha (TNF-alpha). Cycloheximide (CHI) at 10 microg/ml, which inhibited protein synthesis for 80%, caused a 80-fold induction of IL-6 mRNA level which was due predominantly to a stabilization of IL-6 mRNA (20-fold) early on. Employing transient transfection protocols we noted a small positive effect of CHI on transcription, mediated by the proximal and the distal C/EBP sites of the IL-6 promoter and paralleled by an increased C/EBP DNA-binding activity, similar to that found for exposure to TNF-alpha alone. TNF-alpha and CHI synergized on IL-6 mRNA expression (200-fold increase) which was due to an increased transcription, corresponding to a further increased C/EBP DNA-binding activity. However, the effect of CHI on IL-6 gene transcription was transient, in support of the need for ongoing protein synthesis for C/EBP activity. These findings indicate that IL-6 mRNA superinduction, at least in H292 cells, is regulated predominantly by modulating the repressive system that ensures a rapid degradation of IL-6 mRNA.
CCAAT-Enhancer-Binding Proteins↗
Enhanced AP-1 and NF-kappaB activities and stability of interleukin 8 (IL-8) transcripts are implicated in IL-8 mRNA superinduction in lung epithelial H292 cells.
Inhibition of protein synthesis may result in superinduction of short-lived transcripts and has been attributed variably to stabilization of transcripts and/or increased gene transcription. Little is known about the kinetics of these processes and relevant transcriptional elements have not been identified. In this study, we describe superinduction of interleukin 8 (IL-8) mRNA, an important inflammatory mediator, in lung epithelial-like H292 cells and identify the underlying molecular mechanisms and their kinetics. Cycloheximide (CHI, 10 microg/ml), an inhibitor of protein synthesis, maximally increased IL-8 mRNA levels 30-fold in H292 cells. Tumour necrosis factor alpha (TNF-alpha), which induced IL-8 mRNA 3-fold, synergized with CHI causing a 150-fold increase at 6 h. CHI early on increased the stability of IL-8 mRNA (from 40 min in cells cultured with medium to more than 4 h with CHI). CHI also increased transcription as shown by transfection with IL-8 promoter constructs. Truncated and mutated constructs identified NF-kappaB and AP-1 binding sites as primary cis-acting elements in IL-8 gene transcription and IL-8 mRNA superinduction. Electrophoretic mobility shift assays indicated that CHI increased NF-kappaB and prolonged AP-1 DNA-binding activities and that the synergism of TNF-alpha and CHI on IL-8 mRNA expression was paralleled by a further increase of AP-1 DNA-binding activity. This synergism was still noticed when 4 h elapsed between the addition of CHI and that of TNF-alpha. Taken together, our results indicate that CHI interferes with both post-transcriptional and transcriptional repressive mechanisms of IL-8 mRNA expression.
Cell Nucleus↗
Cecal infarct: report of a case.
PURPOSE: The purpose of this article is to present a case of an uncommon opportunistic fungal infection that appears in immunologically or metabolically compromised patients and is usually fatal. METHOD: A 54-year-old woman with an acute lymphoblastic leukemia had acute abdominal pain with peritoneal symptoms during her hospital stay. A laparotomy was performed and a cecal infarct firmly adherent to about 30 cm of infiltrated jejunal loop was discovered. RESULTS: Microscopic studies revealed an infiltration of the jejunal wall by abnormal lymphocytes. The cecal and ileal walls were infiltrated by leukocytes. Blood vessels were invaded by giant cells and large, unseptated, right-angle branching hyphea. CONCLUSIONS: These findings were considered typical of invasive mucormycosis of the cecum and the terminal ileum.
Cecal Diseases↗
[An experimental study of a new bidirectional distraction appliance].
The goals of mandibular distraction are to restore a normal length but also a normal shape to the hypoplastic mandible. These two goals are related to the elongation vector which is itself related to the location of the cortictomy and of the device. Other factors influence this elongation vector. So it is impossible to precisely predict the elongation vector. With the monodirectional distraction device no modification can be made during the distraction time. With a bidirectional distraction device offering the possibility to modulate the angulation between the two elongation rods it is possible to adjust the elongation vector during distraction. Precise distraction gap modeling is possible. This is particularly important to correct anterior open-bite. This device was tested on animals (pigs).
Animals↗
Mediastinal extramedullary hematopoiesis.
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Adult↗
Conservation of Tcrg-V5 and limited allelic sequence polymorphism of the other Tcrg-V genes used by mouse tissue-specific gd-T lymphocytes.
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Alleles↗
[Functional magnetic resonance imaging (MRI) of hepatic ischemia in the rabbit. Contribution of a particulated contrast agent (AMI-25)].
A functional approach of the rabbit portal ischemia was performed on five New Zealand rabbits using magnetic-resonance (MR) imaging and an MR-specific contrast agent for the liver. The hepatic vascularization and the functionality of the phagocytosis cells were both studied with a single low dose of a unique contrast agent-superparamagnetic iron oxide particles (SPIOs). After a rapid i.v. injection of SPIOs, functional vessels and normally perfused liver parenchyma appeared with positive signal enhancement, whereas the ischemic area remained dark (cold spot). After the intravascular time period, the well-known negative enhancement induced by these particles on normal parenchyma was observed, with the difference of the ischemic liver, and could be related to the uptake of SPIOs by functional Kupffer cells.
Animals↗
[Imaging of acquired pathologies of the thoracic aorta].
For many years, imaging of thoracic aorta has been dominated by angiography. Development of new imaging modalities has modified the diagnostic approach to thoracic aortic pathology. The knowledge of the advantages and limitations of each technique enables a better choice for patient evaluation, in particular under emergency conditions. This study is based on a review of the literature and reports the authors' experience.
Aortic Dissection↗
Critical role of endogenous Mtv in acute lethal graft-versus-host disease.
Little is known about the etiology of the graft-versus-host disease (GVHD) occuring after transplantation of lymphoid cells incompatible for minor histocompatibility antigens (mHAg). Here, the potential role of host endogenous mouse mammary tumor virus (Mtv)-encoded superantigens (SAg) in the development of lethal GVHD was investigated. In a combination of H-2d compatible mice, the presence of Mtv-7 and, to a lesser extent, of Mtv-1, -6, -13 in the host genome, highly increases the rate and severity of GVHD. Kinetic analyses of TCR V beta gene expression in recipient mice consistently indicate a dramatic but transient infiltration of GVHD target organs by Mtv-SAg-specific T cells. This suggests that SAg encoded by endogenous Mtv, by activating large T cell subpopulations, would help the response to mHAg and thus play a critical role in the initiation or aggravation of GVHD.
Acute Disease↗