A 32-year-old man with type-1 neurofibromatosis (NF1) was diagnosed with a left vertebral artery aneurysm of 4 cm maximal diameter. A hybrid procedure was conducted associating the exclusion of the origin of the left vertebral artery with a covered stent in the left subclavian artery and a cervical incision for ligation of the vertebral artery to completely exclude the aneurysm and perform the aneurysm resection. The histologic findings confirmed the diagnosis of NF1 with a vascular localization in the aneurysm. The postoperative course was uneventful. The 1-year clinical and morphologic results were satisfactory.
The long-term follow-up of patients with endovascular aneurysm repair (EVAR) and a normal surgical risk was defined by the French National Authority for Health (Haute Autorité de Santé) in 2009. The monitoring of the volume of the aneurysm sac theoretically avoids the bias related to the measurement of its diameter alone. The objective of this study was to evaluate how reliable and reproducible the volumetric measurement of the aneurysm sac by ultrasound was compared with computerized tomography angiography (CTA).
Radiation-induced stenosis of the carotid artery is considered a challenging entity for direct revascularization. We performed a carotid artery stenting for a radiation-induced stenosis using a transapical approach on an asymptomatic 63-year-old male patient. Transapical approach, which is often used for cardiac surgery, was not yet described for the endovascular treatment of carotid stenosis. The transapical approach could be an attractive alternative path for patients presenting significant supra-aortic trunks lesions and unfit for direct approach or peripheral access. This case reports the feasibility and the safety of carotid artery stenting using the transapical approach in well-trained teams.
Radionuclide- and heavy metal-contaminated subsurface sediments remain a legacy of Cold War nuclear weapons research and recent nuclear power plant failures. Within such contaminated sediments, remediation activities are necessary to mitigate groundwater contamination. A promising approach makes use of extant microbial communities capable of hydrolyzing organophosphate substrates to promote mineralization of soluble contaminants within deep subsurface environments.
Brown adipose tissue (BAT) plays a pivotal role in promoting energy expenditure by the virtue of uncoupling protein-1 (UCP-1) that differentiates BAT from its energy storing white adipose tissue (WAT) counterpart. The clinical implication of "classical" BAT (originates from Myf5 positive myoblastic lineage) or the "beige" fat (originates through trans-differentiation of WAT) activation in improving metabolic parameters is now becoming apparent. However, the inducers and endogenous molecular determinants that govern the lineage commitment and differentiation of classical BAT remain obscure. We report here that in the absence of any forced gene expression, stimulation with bone morphogenetic protein 6 (BMP6) induces brown fat differentiation from skeletal muscle precursor cells of murine and human origins. Through a comprehensive transcriptional profiling approach, we have discovered that two days of BMP6 stimulation in C2C12 myoblast cells is sufficient to induce genes characteristic of brown preadipocytes. This developmental switch is modulated in part by newly identified regulators, Optineurin (Optn) and Cyclooxygenase-2 (Cox2). Furthermore, pathway analyses using the Causal Reasoning Engine (CRE) identified additional potential causal drivers of this BMP6 induced commitment switch. Subsequent analyses to decipher key pathway that facilitates terminal differentiation of these BMP6 primed cells identified a key role for Insulin Like Growth Factor-1 Receptor (IGF-1R). Collectively these data highlight a therapeutically innovative role for BMP6 by providing a means to enhance the amount of myogenic lineage derived brown fat.
This study compares the neurologic evolution and number of restenoses between 2 groups of patients who underwent internal carotid endarterectomy with patch angioplasty (CEP): one group with systematic intraoperative completion arteriography (CA) and another group without.
The purpose of this study was to evaluate short-term results of endovascular treatment of common iliac artery (CIA) aneurysms without a distal neck by using iliac branch devices (IBDs), which enable maintenance of antegrade perfusion to the internal iliac artery (IIA).
Ectopic expression of CAAT/enhancer binding protein ? (C/EBP?) in p210BCR/ABL-expressing cells induces granulocytic differentiation, inhibits proliferation, and suppresses leukemogenesis. To dissect the molecular mechanisms underlying these biological effects, C/EBP?-regulated genes were identified by microarray analysis in 32D-p210BCR/ABL cells. One of the genes whose expression was activated by C/EBP? in a DNA binding-dependent manner in BCR/ABL-expressing cells is the transcriptional repressor Gfi-1. We show here that C/EBP? interacts with a functional C/EBP binding site in the Gfi-1 5-flanking region and enhances the promoter activity of Gfi-1. Moreover, in K562 cells, RNA interference-mediated downregulation of Gfi-1 expression partially rescued the proliferation-inhibitory but not the differentiation-inducing effect of C/EBP?. Ectopic expression of wild-type Gfi-1, but not of a transcriptional repressor mutant (Gfi-1P2A), inhibited proliferation and markedly suppressed colony formation but did not induce granulocytic differentiation of BCR/ABL-expressing cells. By contrast, Gfi-1 short hairpin RNA-tranduced CD34(+) chronic myeloid leukemia cells were markedly more clonogenic than the scramble-transduced counterpart. Together, these studies indicate that Gfi-1 is a direct target of C/EBP? required for its proliferation and survival-inhibitory effects in BCR/ABL-expressing cells.
The transcription factor C/EBP? is more potent than C/EBP? in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a "domain swapping" approach to assess biological effects, modulation of gene expression, and binding to C/EBP?-regulated promoters by wild-type and chimeric C/EBP?/C/EBP? proteins. Wild-type and N-C/EBP?+ C/EBP?-DBD induced transcription of the granulocyte-colony stimulating factor receptor (G-CSFR) gene, promoted differentiation, and suppressed proliferation of K562 cells vigorously; instead, wild-type C/EBP? and N-C/EBP?+C/EBP?-DBD had modest effects, although they bound the G-CSFR promoter like wild-type C/EBP? and N-C/EBP?+C/EBP?-DBD. Chimeric proteins consisting of the TAD of VP16 and the DBD of C/EBP? or C/EBP? inhibited proliferation and induced differentiation of K562 cells as effectively as wild-type C/EBP?. Gene expression profiles induced by C/EBP? resembled those modulated by N-C/EBP?+C/EBP?-DBD, whereas C/EBP? induced a pattern similar to that of N-C/EBP?+C/EBP?-DBD. C/EBP? activation induced changes in the expression of more cell cycle- and apoptosis-related genes than the other proteins and enhanced Imatinib-induced apoptosis of K562 cells. Expression of FOXO3a, a novel C/EBP?-regulated gene, was required for apoptosis but not for differentiation induction or proliferation inhibition of K562 cells.
Extraskeletal myxoid chondrosarcoma is a rare tumor with less than 100 cases reported in the literature. The prevalence of anti-Hu positive myxoid chondrosarcoma-associated paraneoplastic subacute cerebellar degeneration is exceedingly rare. We present a report of a patient with confirmed myxoid chondrosarcoma-associated paraneoplastic subacute cerebellar degeneration, who exhibited marked improvement within 1 week of receiving chemotherapy, intravenous immunoglobulin (IVIG), and hydrocortisone treatment.
Vibrio parahaemolyticus is a pathogenic marine bacterium that is the main causative agent of bacterial seafood-borne gastroenteritis in the United States. An increase in the frequency of V. parahaemolyticus-related infections during the last decade has been attributed to the emergence of an O3:K6 pandemic clone in 1995. The diversity of the O3:K6 pandemic clone and its serovariants has been examined using multiple molecular techniques including multilocus sequence analysis, pulsed-field gel electrophoresis, and group-specific PCR analysis. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has become a powerful tool for rapidly distinguishing between related bacterial species. In the current study, we demonstrate the development of a whole-cell MALDI-TOF MS method for the distinction of V. parahaemolyticus from other Vibrio spp. We identified 30 peaks that were present only in the spectra of the V. parahaemolyticus strains examined in this study that may be developed as MALDI-TOF MS biomarkers for identification of V. parahaemolyticus. We detected variation in the MALDI-TOF spectra of V. parahaemolyticus strains isolated from different geographical locations and at different times. The MALDI-TOF MS spectra of the V. parahaemolyticus strains examined were distinct from those of the other Vibrio species examined including the closely related V. alginolyticus, V. harveyi, and V. campbellii. The results of this study demonstrate the first use of whole-cell MALDI-TOF MS analysis for the rapid identification of V. parahaemolyticus.
The results of the endovascular treatment of external iliac artery lesions in patients with claudication are not well known. In the literature, very often, the studied populations are not homogenous (people with claudication and with acute ischemia) and the external iliac artery is not differentiated from the primary iliac artery. Moreover, systematic stenting is still debated. Our goal was to study the results of systematic stenting for atheromatous lesions of the external iliac artery in a consecutive and homogenous population of patients with claudication. From June 2000 to December 2006, 90 external iliac arteries were treated with systematic stenting for atheromatous lesions in 81 consecutive patients with claudication (74 men and 7 women, aged 62+/-12 years). Lesions were classified according to the Trans-Atlantic Intersociety Consensus (TASC). Endovascular treatment was systematically chosen for TASC A (n=40) and B (n=30) patients and patients at high surgical risk for TASC C (n=18) and D (n=2). One hundred and seven stents were placed; they were 37+/-21 mm long with a 7+/-0.6mm diameter. Clinical examination and duplex follow-up were carried out at a minimum of 3 months and at the end of the follow-up. There was a 2.2% complication rate, without any deaths (retroperitoneal hematoma). Mean follow-up was 23 months (with a 13-month median). Primary patency rate was 97% (standard error [SE] 2%) at 1 year, 90% (SE 4.6%) at 2 years, and 84% (SE 6.6%) at 3 years. Secondary patency rate was 98% (SE 1.5%) at 1 year, 93% (SE 3.9%) at 2 years, and 93% (SE 4.5%) at 3 years. Ten restenoses were detected and treated by endovascular techniques (n=6), bypass (n=2), or medication (n=2). At the end of the follow-up, the patients were asymptomatic (n=62) or presented with a moderate (n=17) or severe (n=8) claudication. A patient with hemodialysis was amputated at the metatarsal level. No significant predictive restenosis factor was discovered. However, the C or D TASC classification seemed to favor an earlier restenosis (p=0.06). In conclusion, our study demonstrates that, in a larger population than in the literature, systematic stenting on the external iliac artery gives satisfying results in patients with claudication.
Many important biological processes are controlled through cell-cell interactions, including the colonization of metastatic tumor cells and the control of differentiation of stem cells within their niche. Despite the crucial importance of the cellular environment in regulating cellular signaling, in vitro methods for the study of such interactions are difficult and/or indirect.
Oxidized low-density lipoprotein (OxLDL) has been implicated as a proatherogenic factor with a pathological role in the induction of endothelial dysfunction. Endothelial cells bind and uptake OxLDL primarily through the scavenger receptor lectin-like oxidized-low-density lipoprotein receptor-1 (LOX-1), which is believed to mediate critical effects of OxLDL in endothelial cells. To examine the biological events following LOX-1 activation by OxLDL, we used cDNA microarray analysis to globally analyze gene expression changes induced by OxLDL treatment of human aortic endothelial cell line (HAECT) cells overexpressing LOX-1. Consistent with reported functions of OxLDL, in control HAECT cells, OxLDL elicited gene changes in the oxidative stress pathway and other signaling pathways related to OxLDL. With OxLDL treatment, LOX-1-dependent gene expression changes associated with inflammation, cell adhesion, and signal transduction were observed. The transcripts of a number of cytokines and chemokines were induced, which included interleukin-8, CXCL2, CXCL3, and colony-stimulating factor-3. The secretion of these cytokines was confirmed by enzyme-linked immunosorbent assay analysis. In addition, our data revealed a novel link between LOX-1 and a number of genes, including Delta/notch-like epidermal growth factor repeat containing, stanniocalcin-1, cAMP response element modulator, and dual specificity phosphatase 1. Promoter analysis on the genes that changed as a result of LOX-1 activation by OxLDL allowed us to identify early growth response 1 and cAMP response element-binding protein as potential novel transcription factors that function downstream of LOX-1. Our study has enabled us to elucidate the gene expression changes following OxLDL activation of LOX-1 in endothelial cells and discover novel downstream targets for LOX-1.
Adipocyte-secreted proteins play important roles in metabolic regulation through autocrine, paracrine, and endocrine mechanisms. Using transcriptional profiling, we identified coiled-coil domain containing 80 (Ccdc80; also known as DRO1 and URB) as a novel secreted protein highly expressed in white adipose tissue. In 3T3-L1 cells Ccdc80 is expressed and secreted in a biphasic manner with high levels in postconfluent preadipocytes and terminally differentiated adipocytes. To determine whether Ccdc80 regulates adipocyte differentiation, Ccdc80 expression was manipulated using both knockdown and overexpression approaches. Small hairpin RNA-mediated silencing of Ccdc80 in 3T3-L1 cells inhibits adipocyte differentiation. This phenotype was partially reversed by treating the knockdown cells with Ccdc80-containing conditioned medium from differentiated 3T3-L1 cells. Molecular studies indicate that Ccdc80 is required for the full inhibition of T-cell factor-mediated transcriptional activity, down-regulation of Wnt/beta-catenin target genes during clonal expansion, and the subsequent induction of C/EBPalpha and peroxisome proliferator-activated receptor gamma. Surprisingly, overexpression of Ccdc80 in 3T3-L1 cells also inhibits adipocyte differentiation without affecting the repression of the Wnt/beta-catenin signaling pathway. Taken together, these data suggest that Ccdc80 plays dual roles in adipogenesis by mechanisms that involve at least in part down-regulation of Wnt/beta-catenin signaling and induction of C/EBPalpha and peroxisome proliferator-activated receptor gamma.
The nuclear hormone receptor farnesoid X receptor (FXR) plays a critical role in the regulation of bile acid, triglyceride (TG), and cholesterol homeostasis. WAY-362450 (FXR-450/XL335) is a potent synthetic FXR agonist as characterized in luciferase reporter assays and in mediating FXR target gene regulation in primary human and immortalized mouse hepatocytes. In vivo, WAY-362450 dose dependently decreased serum TG levels after 7 days of oral dosing in western diet-fed low-density lipoprotein receptor-/- mice and in the diabetic mouse strains KK-Ay and db/db comparable to that achieved with the peroxisome proliferator activated receptor-alpha agonist, fenofibrate. WAY-362450 treatment also reduced serum cholesterol levels via reductions in LDLc, VLDLc, and HDLc lipoprotein fractions that were not accompanied by hepatic cholesterol accumulation. This cholesterol lowering was dependent on FXR as demonstrated in a hypothyroid-induced hypercholesterolemia setting in FXR-/- mice. In fructose-fed models, WAY-362450 also decreased TG and VLDLc levels in rats and hamsters but significantly increased HDLc levels in rats while reducing HDLc levels in hamsters. The differential effect of WAY-362450 on HDLc is likely due to a murine-specific induction of endothelial lipase and scavenger receptor-BI that does not occur in rats. These studies demonstrate a consistent ability of WAY-362450 to lower both serum TG and cholesterol levels and suggest that synthetic FXR agonists may have clinical utility in the treatment of mixed dyslipidemia.
Coastal salt marshes are highly sensitive wetland ecosystems that can sustain long-term impacts from anthropogenic events such as oil spills. In this study, we examined the microbial communities of a Gulf of Mexico coastal salt marsh during and after the influx of petroleum hydrocarbons following the Deepwater Horizon oil spill. Total hydrocarbon concentrations in salt marsh sediments were highest in June and July 2010 and decreased in September 2010. Coupled PhyloChip and GeoChip microarray analyses demonstrated that the microbial community structure and function of the extant salt marsh hydrocarbon-degrading microbial populations changed significantly during the study. The relative richness and abundance of phyla containing previously described hydrocarbon-degrading bacteria (Proteobacteria, Bacteroidetes, and Actinobacteria) increased in hydrocarbon-contaminated sediments and then decreased once hydrocarbons were below detection. Firmicutes, however, continued to increase in relative richness and abundance after hydrocarbon concentrations were below detection. Functional genes involved in hydrocarbon degradation were enriched in hydrocarbon-contaminated sediments then declined significantly (p<0.05) once hydrocarbon concentrations decreased. A greater decrease in hydrocarbon concentrations among marsh grass sediments compared to inlet sediments (lacking marsh grass) suggests that the marsh rhizosphere microbial communities could also be contributing to hydrocarbon degradation. The results of this study provide a comprehensive view of microbial community structural and functional dynamics within perturbed salt marsh ecosystems.
The biotransformation of n-tetradecylbenzyldimethylammonium chloride (C(14)BDMA-Cl), a quaternary ammonium compound (QAC), under aerobic conditions by an enriched microbial community growing on benzalkonium chlorides (BACs) was investigated. Biotransformation of C(14)BDMA-Cl commenced with cleavage of the C(alkyl)-N bond and formation of benzyldimethylamine (BDMA). BDMA was further degraded, but in contrast to a previously reported BAC biotransformation pathway, neither benzylmethylamine (BMA) nor benzylamine (BA) was detected as a BDMA biotransformation product. Kinetic assays further confirmed that BMA and BA were not intermediates of C(14)BDMA-Cl transformation by the enriched community. Thus, BDMA is thought to be transformed to dimethylamine and benzoic acid via debenzylation. The biomass-normalized rate of C(14)BDMA-Cl biotransformation was 0.09 ?mol/[mg of volatile suspended solids (VSS)·h]. The Microtox acute toxicity EC(50) value of BDMA was 500 times higher than that of C(14)BDMA-Cl. Thus, the aerobic biotransformation of C(14)BDMA-Cl to BDMA results in substantial toxicity reduction. Phylogenetic analysis of Bacteria diversity indicated that the majority of the sequenced clones (98% of the clone library) belonged to the genus Pseudomonas.
Coiled-coil domain containing 80 (Ccdc80) is a secreted protein highly enriched in mouse and human white adipose tissue (WAT) that plays an important role during adipocyte differentiation in vitro. To investigate the physiological function of Ccdc80 in energy and glucose homeostasis, we generated mice in which the gene encoding Ccdc80 was disrupted. Mice lacking Ccdc80 showed increased sensitivity to diet-induced hyperglycemia and glucose intolerance while displaying reduced glucose-stimulated insulin secretion in vivo. Gene expression analysis by microarray revealed that only 10 transcripts were simultaneously altered in pancreas, skeletal muscle, and WAT from Ccdc80(-/-) mice, including some components of the circadian clock. Expression of the core clock member Arntl/Bmal1 was reduced whereas that of the oscillating transcription factors Dbp and Tef was increased in all tissues examined. Furthermore, knockdown of Ccdc80 in 3T3-L1 cells led to an increase of Dbp mRNA levels during adipocyte differentiation, suggesting that Ccdc80 might be involved in the regulation of this gene in a cell-autonomous manner. Importantly, transcriptional alterations in Ccdc80(-/-) mice were associated with changes in feeding behavior, increased caloric intake, decreased energy expenditure, and obesity. Taken together, our results suggest that Ccdc80 is a novel modulator of glucose and energy homeostasis during diet-induced obesity.
Rahnella aquatilis CIP 78.65 is a gammaproteobacterium isolated from a drinking water source in Lille, France. Here we report the complete genome sequence of Rahnella aquatilis CIP 78.65, the type strain of R. aquatilis.
Rahnella sp. strain Y9602 is a gammaproteobacterium isolated from contaminated subsurface soils that is capable of promoting uranium phosphate mineralization as a result of constitutive phosphatase activity. Here we report the first complete genome sequence of an isolate belonging to the genus Rahnella.
Positron emission tomography (PET) provides spatiotemporal monitoring in a nondestructive manner and has higher sensitivity and resolution relative to other tomographic methods. Therefore, this technology was evaluated for its application to monitor in situ subsurface bacterial activity. To date, however, it has not been used to monitor or image soil microbial processes. In this study, PET imaging was applied as a "proof-of-principle" method to assess the feasibility of visualizing a radiotracer labeled subsurface bacterial strain (Rahnella sp. Y9602), previously isolated from uranium contaminated soils and shown to promote uranium phosphate precipitation. Soil columns packed with acid-purified simulated mineral soils were seeded with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)FDG) labeled Rahnella sp. Y9602. The applicability of [(18)F]fluoride ion as a tracer for measuring hydraulic conductivity and (18)FDG as a tracer to identify subsurface metabolically active bacteria was successful in our soil column studies. Our findings indicate that positron-emitting isotopes can be utilized for studies aimed at elucidating subsurface microbiology and geochemical processes important in contaminant remediation.
Based on its homology to the estrogen receptor and its roles in osteoblast and chondrocyte differentiation, the orphan nuclear receptor estrogen-related receptor ? (ERR? (ESRRA)) is an intriguing therapeutic target for osteoporosis and other bone diseases. The objective of this study was to better characterize the molecular mechanisms by which ERR? modulates osteoblastogenesis. Experiments from multiple systems demonstrated that ERR? modulates Wnt signaling, a crucial pathway for proper regulation of bone development. This was validated using a Wnt-luciferase reporter, where ERR? showed co-activator-dependent (peroxisome proliferator-activated receptor gamma co-activator 1?, PGC-1?) stimulatory effects. Interestingly, knockdown of ERR? expression also enhanced WNT signaling. In combination, these data indicated that ERR? could serve to either activate or repress Wnt signaling depending on the presence or absence of its co-activator PGC-1?. The observed Wnt pathway modulation was cell intrinsic and did not alter ?-catenin nuclear translocation but was dependent on DNA binding of ERR?. We also found that expression of active ERR? correlated with Wnt pathway effects on osteoblastic differentiation in two cell types, consistent with a role for ERR? in modulating the Wnt pathway. In conclusion, this work identifies ERR?, in conjunction with co-activators such as PGC-1?, as a new regulator of the Wnt-signaling pathway during osteoblast differentiation, through a cell-intrinsic mechanism not affecting ?-catenin nuclear translocation.
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