17 results on '"MCP"'
Search Results
2. Why local banking market concentration hinders IPOs and how it can work to issuers’ advantage
- Author
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Antonios Kallias, Song Zhang, Guancheng Lu, Konstantinos Kallias, and University of St Andrews. School of Management
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050208 finance ,Initial public offerings ,HG Finance ,05 social sciences ,Monetary economics ,3rd-DAS ,Venture capital ,Market concentration ,HG ,Banking market concentration ,Market structure ,Spillover effect ,Soft information ,Issuer ,MCP ,0502 economics and business ,Business ,Market power ,050207 economics ,Listing (finance) ,Initial public offering ,Finance - Abstract
General sample evidence conceals the influence of banking market structure on a fraction of IPO issuers with limited financing options: small non-venture-capital-backed firms (SNVC). Using U.S. county-level data, we reveal that concentrated banking markets contract IPO activity, as they cause SNVCs to incur high underpricing at listing. However, when the size of the local banks is small, both the time to IPO and underpricing decrease. Our evidence infers that, unless banks are organizationally capable of tapping into soft information, they generally use market power for rent extraction, which has important spillover effects on the IPO market. Postprint
- Published
- 2021
3. Immobilization of MIL-88(Fe) anchored TiO 2 -chitosan(2D/2D) hybrid nanocomposite for the degradation of organophosphate pesticide: Characterization, mechanism and degradation intermediates.
- Author
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Vigneshwaran S, Sirajudheen P, Karthikeyan P, Nikitha M, Ramkumar K, and Meenakshi S
- Abstract
In this study, we have rationally designed and grafted a bio-assisted 2D/2D TiO
2 /MIL-88(Fe) (TCS@MOF) heterojunction by growing granular TiO2 on the surface of MIL-88(Fe) nanosheet, as hybrid photocatalyst. The hierarchical TCS@MOF composite was prepared via the one-pot solvothermal process and employed for monocrotophos (MCP) degradation under visible light region, since its persistent nature on soil and water causes major threat to the environment. The TCS@MOF promotes a number of packed high-speed nano-tunnels in the (p-n) heterojunctions, which significantly enhance the migration of photo-induced electrons (e- ) and holes (h+ ), respectively and thus limits the charge recombination of e- s. The optimized photocatalyst achieves significant catalytic activity of ~98.79% for the degradation of MCP within 30 min of irradiation. The prominent oxidative radicals namely •OH, •O2 etc., were involved in the oxidation of organic pesticide. Besides, TCS@MOF exhibits outstanding stability even after five repetitive cycles for the oxidation of MCP with a negligible decrease in photo-activity. The proposed mechanism and oxidative pathways of MCP were rationally deduced in detail subject to experimental results. The mechanism renders insight into the oxidation and consequent bond rupture of pollutant as well as into the formation of products such as H- etc., were involved in the oxidation of organic pesticide. Besides, TCS@MOF exhibits outstanding stability even after five repetitive cycles for the oxidation of MCP with a negligible decrease in photo-activity. The proposed mechanism and oxidative pathways of MCP were rationally deduced in detail subject to experimental results. The mechanism renders insight into the oxidation and consequent bond rupture of pollutant as well as into the formation of products such as H2 O, CO2 , etc. This report unveils a novel architecture of proficiently optimized TCS@MOF material structure for the perceptive oxidation of organic contaminants., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2021
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4. The molecular and structural bases for the association of complement C3 mutations with atypical hemolytic uremic syndrome
- Author
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Martínez-Barricarte, Rubén, López-Perrote, Andrés, Tortajada, Agustín, Pinto, Sheila, Llorca, Óscar, and Rodríguez de Córdoba, Santiago
- Subjects
Atypical hemolytic uremic syndrome ,MCP ,Factor H ,C3 mutation ,Complement C3 ,TED - Abstract
44 p.-7 fig.-1 tab.Martínez-Barricarte, Rubén et alt., Atypical hemolytic uremic syndrome (aHUS) associates with complement dysregulation caused by mutations and polymorphisms in complement activators and regulators. However, the reasons why some mutations in complement proteins predispose to aHUS are poorly understood. Here, we have investigated the functional consequences of three aHUS-associated mutations in C3, R592W, R161W and I1157T. First, we provide evidence that penetrance and disease severity for these mutations is modulated by inheritance of documented “risk” haplotypes as has been observed with mutations in other complement genes. Next, we show that all three mutations markedly reduce the efficiency of factor I-mediated C3b cleavage when catalysed by membrane cofactor protein (MCP), but not when catalysed by factor H. Biacore analysis showed that each mutant C3b bound sMCP (recombinant soluble MCP; CD46) at reduced affinity, providing a molecular basis for its reduced cofactor activity. Lastly, we show by electron microscopy structural analysis a displacement of the TED domain from the MG ring in C3b in two of the C3 mutants that explains these defects in regulation. As a whole our data suggest that aHUS-associated mutations in C3 selectively affect regulation of complement on surfaces and provide a structural framework to predict the functional consequences of the C3 genetic variants found in patients., Work in this report has been funded by the Spanish “Ministerio de Economía y Competitividad” (SAF2011-26583 to SRdeC, PI12-00597 to PS-C and SAF2011-22988 to OL), the Fundación Renal Iñigo Alvarez de Toledo, the Seventh Framework Programme European Union Project EURenOmics (305608) to SRdeC, by a grant from the Autonomous Region of Madrid (S2010/BMD-2316) to SRdeC and OL and the Medical Research Council, United Kingdom (G0701298) to CLH and BPM.
- Published
- 2015
5. Outcomes Following Acute Metacarpophalangeal Joint Arthroplasty Dislocation: An Analysis of 37 Cases.
- Author
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Wanderman N, Wagner E, Moran S, and Rizzo M
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- Adult, Aged, Aged, 80 and over, Carbon, Female, Humans, Immobilization, Joint Capsule surgery, Ligaments, Articular surgery, Male, Middle Aged, Reoperation statistics & numerical data, Retrospective Studies, Silicones, Splints, Tendons surgery, Tissue Adhesions surgery, Arthroplasty, Replacement, Finger adverse effects, Joint Dislocations therapy, Joint Prosthesis adverse effects, Metacarpophalangeal Joint surgery, Prosthesis Failure
- Abstract
Purpose: There remains a paucity of information regarding the treatment outcomes of dislocation after metacarpophalangeal (MCP) joint arthroplasty. The purpose of this study was to assess the outcomes of surgical and nonsurgical treatment modalities of MCP arthroplasty dislocations., Methods: Of 816 MCP joint arthroplasties over a 14-year period, there were 37 (4%) acute MCP joint dislocations that required intervention by a health care professional. Implants involved included 28 nonconstrained implants including pyrocarbon (n = 17) and surface replacement arthroplasty (n = 11), and 9 silicone implants. The analysis included the treatment of dislocations after primary (n = 30) and revision (n = 7) MCP joint arthroplasty. Dislocation was defined as clinical and radiographic evidence of MCP joint prosthetic acute dislocation diagnosed and treated by a fellowship trained hand surgeon., Results: Etiologies underlying the dislocations included implant fracture (n = 6), component loosening (n = 2), and soft tissue deficiency (n = 29). Of the 37 dislocations, treatments included 14 nonsurgical (closed reduction, orthosis fabrication) all of which ultimately failed. Surgically, including some of the failed prior procedures, 18 soft tissue stabilization procedures and 21 revision arthroplasties were performed, with 6 that had failed soft tissue stabilization. The soft tissue stabilization procedures had a 28% success rate in achieving a stable MCP joint. Revision arthroplasty had a 71% success rate. Subgroup analysis showed an 86% success rate for silicone revisions and a 43% success rate with nonconstrained revisions, with 80% and 36% 5-year survival free of instability, for the 2 types of implants, respectively., Conclusions: The treatment of MCP joint arthroplasty dislocation with revision to silicone implant appears to hold the most promise in achieving a stable MCP joint after an acute prosthetic dislocation., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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6. Silicone Metacarpophalangeal Arthroplasty for Osteoarthritis: Long-Term Results.
- Author
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Morrell NT and Weiss AC
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Collateral Ligaments surgery, Female, Follow-Up Studies, Humans, Male, Metacarpophalangeal Joint diagnostic imaging, Middle Aged, Osteoarthritis diagnostic imaging, Range of Motion, Articular, Retrospective Studies, Silicones, Visual Analog Scale, Arthroplasty, Replacement, Finger, Joint Prosthesis, Metacarpophalangeal Joint surgery, Osteoarthritis surgery
- Abstract
Purpose: To demonstrate that silicone metacarpophalangeal (MCP) arthroplasty provides excellent long-term outcomes with a low complication rate in osteoarthritis patients., Methods: A consecutive cohort of 35 patients with osteoarthritis of 1 or more MCP joints undergoing anatomically neutral silicone MCP arthroplasty was followed over a 15-year period. Functional outcomes including strength and range of motion (ROM), as well as complications, were recorded. All patients were available for long-term assessment including radiographs and outcomes questionnaire., Results: Average follow-up for the cohort of 35 patients (40 implants) was 8.3 years (range, 2-17 years). Average age was 58 years (range, 42-80 years) with 22 men and 13 women. In 31 patients, a single MCP joint was involved (middle finger, 20; index finger, 10; little finger, 1). The dominant hand was involved in 23 patients. Seven (of 14) patients had a concomitant RCL reconstruction of the index finger MCP joint; no other digit had a collateral ligament reconstruction. Average final visual analog scale pain score was 0.3 of 10. Average final active ROM arc was from 4° (range, 0°-20°) to 73° (range, 50°-90°) of flexion. One patient had a revision MCP arthroplasty for a 97% clinical survivorship. Radiographs demonstrated fractured implants in 5 of 40 (12.5%) implants, but none exhibited instability, pain, or ROM deterioration. Average Michigan Hand Outcomes Questionnaire score was 82 (of 100) at final follow-up., Conclusions: Silicone arthroplasty is effective in the treatment of primary MCP osteoarthritis. Implant survivorship is 97% (clinical) and 88% (radiographic) in long-term follow-up., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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7. Factor associated variations in the home range of a resident Adriatic common bottlenose dolphin population.
- Author
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Rako-Gospić N, Radulović M, Vučur T, Pleslić G, Holcer D, and Mackelworth P
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- Animals, Croatia, Female, Homing Behavior, Male, North Sea, Sex Characteristics, Bottle-Nosed Dolphin physiology
- Abstract
This study investigates the influence of the most dominant factors (association patterns, gender, natal philopatry and anthropogenic pressure) on the home range size of the 44 most resident common bottlenose dolphins (Tursiops truncatus) inhabiting the waters of the Cres-Lošinj archipelago (north Adriatic Sea, Croatia), a recently declared NATURA 2000 SCI. Results show that variations in home range patterns (MCP, 95% KDE and 50% KDE home range size) among the individual resident dolphins are primarily related to differences in gender and reflect the way in which different genders respond to external stressors. In addition, results confirm the seasonal influence of nautical tourism on both female and male dolphins through changes in their home range sizes. The overall results improve current knowledge of the main anthropogenic threats that should be taken into consideration when developing conservation measures to be applied to this Cres and Lošinj SCI., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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8. Implant Arthroplasty for Proximal Interphalangeal, Metacarpophalangeal, and Trapeziometacarpal Joint Degeneration.
- Author
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Srnec JJ, Wagner ER, and Rizzo M
- Subjects
- Arthritis diagnostic imaging, Arthritis etiology, Humans, Joint Prosthesis, Prosthesis Design, Treatment Outcome, Arthritis surgery, Arthroplasty, Replacement, Hand Joints
- Abstract
Arthritis of the hand can result from inflammatory arthritis, osteoarthritis (OA), or be posttraumatic and can cause pain and debilitation. Arthroplasty serves as 1 surgical option in the surgical management of arthritis and aims to create a pain-free joint with preservation of motion. Although implant arthroplasty of the proximal interphalangeal (PIP), metacarpophalangeal (MCP), and trapeziometacarpal (TMC) joints predictably produce pain relief and high satisfaction, it has historically suffered from high rates of complications. The hinged silicone prosthesis was 1 of the early implants and, in many cases, remains the gold standard. However, problems with deformity correction, implant fracture, and synovitis remain. Implants made of alternative materials such as metal-plastic and pyrocarbon have evolved; however, survivorship and reoperation rates remain a concern. This review details the evolution and current options available for small joint implant arthroplasty involving the MCP, PIP, and TMC joints., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2017
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9. Metacarpophalangeal Joint Arthroplasty in the Setting of Trauma.
- Author
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Houdek MT, Wagner ER, Rizzo M, and Moran SL
- Subjects
- Aged, 80 and over, Arthroplasty, Replacement, Finger instrumentation, Carbon, Female, Hand Strength, Humans, Joint Prosthesis, Male, Middle Aged, Pain Measurement, Prosthesis Design, Range of Motion, Articular, Treatment Outcome, Arthroplasty, Replacement, Finger methods, Finger Injuries surgery, Lacerations surgery, Metacarpophalangeal Joint injuries, Metacarpophalangeal Joint surgery
- Abstract
Purpose: To report the outcome of pyrocarbon metacarpophalangeal (MCP) joint implants with traumatic nonreconstructible articular cartilage loss., Methods: We performed a review of all patients at a single institution who underwent a pyrocarbon MCP joint arthroplasty performed after an acute injury. Of 820 MCP joint arthroplasties performed, 10 were performed in 7 patients for open MCP joint trauma within 24 hours of the initial injury. Six were hemi- and 4 were total arthroplasties. The mean follow-up was 4 years. All injuries were the result of a direct laceration over the MCP joint., Results: There were no cases of revision or postoperative infection. Mean total arc of motions for the MCP, proximal interphalangeal, and distal interphalangeal joints were 56° (30° to 70°), 76° (40° to 100°), and 50° (21° to 70°), respectively. Postoperative mean grip, oppositional pinch, and appositional pinch strengths were 28, 9, and 11 kg, respectively. All patients except one reported no or mild pain at the last follow-up. Half of the patients required a tenolysis., Conclusions: MCP joint arthroplasty was performed safely in the setting of acute complex open MCP joint trauma. Patients had preservation of adequate MCP joint motion and experienced little pain. MCP arthroplasty should be a consideration in cases of open MCP joint trauma to preserve motion, prevent pain, and avoid fusion., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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10. Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks
- Author
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Kim, Hyungjun, Kim, Jieun, Loggia, Marco L., Cahalan, Christine, Garcia, Ronald G., Vangel, Mark G., Wasan, Ajay D., Edwards, Robert R., and Napadow, Vitaly
- Subjects
Fibromyalgia ,Pain ,Network ,Tractography ,Cerebellum ,AAL ,automated anatomical labeling ,BDI ,Beck depression inventory ,BPI ,brief pain inventory ,DTI ,diffusion tensor imaging ,FM ,fibromyalgia ,fMRI ,functional MRI ,FSL ,FMRIB software library ,HC ,healthy controls ,MCP ,middle cerebellar peduncle ,MNI ,Montreal neurological institute ,MRI ,magnetic resonance imaging ,ROI ,region of interest ,SCP ,superior cerebellar peduncle ,SPM ,statistical parametric mapping ,P40 ,the pressure level (mm Hg) for a pain intensity rating of 40/100 ,VBM ,voxel-based morphometry - Abstract
Altered brain morphometry has been widely acknowledged in chronic pain, and recent studies have implicated altered network dynamics, as opposed to properties of individual brain regions, in supporting persistent pain. Structural covariance analysis determines the inter-regional association in morphological metrics, such as gray matter volume, and such structural associations may be altered in chronic pain. In this study, voxel-based morphometry structural covariance networks were compared between fibromyalgia patients (N = 42) and age- and sex-matched pain-free adults (N = 63). We investigated network topology using spectral partitioning, which can delineate local network submodules with consistent structural covariance. We also explored white matter connectivity between regions comprising these submodules and evaluated the association between probabilistic white matter tractography and pain-relevant clinical metrics. Our structural covariance network analysis noted more connections within the cerebellum for fibromyalgia patients, and more connections in the frontal lobe for healthy controls. For fibromyalgia patients, spectral partitioning identified a distinct submodule with cerebellar connections to medial prefrontal and temporal and right inferior parietal lobes, whose gray matter volume was associated with the severity of depression in these patients. Volume for a submodule encompassing lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and insular cortices was correlated with evoked pain sensitivity. Additionally, the number of white matter fibers between specific submodule regions was also associated with measures of evoked pain sensitivity and clinical pain interference. Hence, altered gray and white matter morphometry in cerebellar and frontal cortical regions may contribute to, or result from, pain-relevant dysfunction in chronic pain patients.
- Published
- 2015
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11. Effect of carpometacarpal joint osteoarthritis, sex, and handedness on thumb in vivo kinematics.
- Author
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Hamann N, Heidemann J, Heinrich K, Wu H, Bleuel J, Gonska C, and Brüggemann GP
- Subjects
- Adult, Aged, Biomechanical Phenomena physiology, Case-Control Studies, Female, Humans, Male, Middle Aged, Sex Factors, Trapezium Bone, Carpometacarpal Joints physiopathology, Functional Laterality physiology, Metacarpophalangeal Joint physiopathology, Osteoarthritis physiopathology, Range of Motion, Articular physiology, Thumb
- Abstract
Purpose: To investigate the influence of trapeziometacarpal (TMC) osteoarthritis (OA) on the 3-dimensional motion capability of the TMC and thumb metacarpophalangeal (MCP) joints. In order to examine other factors affecting the thumb's motion kinematics, we further aimed to address the influence of sex and handedness on the motion capability of normal TMC and MCP joints., Methods: We included 18 healthy subjects (9 women, 9 men; 8 dominant hands, 10 nondominant hands) and 18 women with stage II/III TMC OA. A motion analysis system using surface markers was used to quantify the thumb's 3-dimensional opposition-reposition kinematics. The range of motion of the thumb's TMC and MCP joints in flexion-extension, abduction-adduction, and pronation-supination were determined., Results: TMC OA led to a loss in abduction-adduction in the TMC joint (38° in controls, 26° in TMC OA subjects), although neither flexion-extension nor pronation-supination were affected. At the MCP joint, the TMC OA subjects showed a 48% reduction in abduction-adduction (32° controls, 16° TMC OA subjects) and 42% reduction in pronation-supination (34° in controls, 20° in TMC OA subjects) than the healthy controls. Ranges of motion of the healthy TMC and MCP joints were similar in dominant and nondominant hands as well as in women and men., Discussion: The study demonstrated that stage II/III TMC OA restricts the motion of the TMC joint in abduction-adduction and of the MCP joint in abduction-adduction and pronation-supination. Thumb motion capability was unaffected by sex and handedness., Clinical Relevance: Osteoarthritis-induced loss of TMC motion did not reflect a generalizable clinical parameter, rather, it seemed to distinctly affect the TMC and the MCP joints and their motion planes and directions. As neither sex nor handedness influenced the motion capabilities of the healthy thumb, kinematic factors contributing to TMC OA may develop at a later age., (Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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12. Beyond gene expression: the impact of protein post-translational modifications in bacteria.
- Author
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Cain JA, Solis N, and Cordwell SJ
- Subjects
- Bacterial Proteins genetics, Mass Spectrometry, Peptides genetics, Bacteria metabolism, Bacterial Proteins metabolism, Gene Expression Regulation, Bacterial physiology, Peptides metabolism, Protein Processing, Post-Translational physiology, Proteomics
- Abstract
The post-translational modification (PTM) of proteins plays a critical role in the regulation of a broad range of cellular processes in eukaryotes. Yet their role in governing similar systems in the conventionally presumed 'simpler' forms of life has been largely neglected and, until recently, was thought to occur only rarely, with some modifications assumed to be limited to higher organisms alone. Recent developments in mass spectrometry-based proteomics have provided an unparalleled power to enrich, identify and quantify peptides with PTMs. Additional modifications to biological molecules such as lipids and carbohydrates that are essential for bacterial pathophysiology have only recently been detected on proteins. Here we review bacterial protein PTMs, focusing on phosphorylation, acetylation, proteolytic degradation, methylation and lipidation and the roles they play in bacterial adaptation - thus highlighting the importance of proteomic techniques in a field that is only just in its infancy. This article is part of a Special Issue entitled: Trends in Microbial Proteomics., (© 2013 Elsevier B.V. All rights reserved.)
- Published
- 2014
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13. Regulation of accumulation and function of myeloid derived suppressor cells in different murine models of hepatocellular carcinoma.
- Author
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Kapanadze T, Gamrekelashvili J, Ma C, Chan C, Zhao F, Hewitt S, Zender L, Kapoor V, Felsher DW, Manns MP, Korangy F, and Greten TF
- Subjects
- Animals, Antineoplastic Agents pharmacology, Carcinoma, Hepatocellular chemically induced, Carcinoma, Hepatocellular metabolism, Diethylnitrosamine adverse effects, Granulocyte-Macrophage Colony-Stimulating Factor metabolism, Heterografts, Humans, Liver Neoplasms chemically induced, Liver Neoplasms metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Myeloid Cells drug effects, Niacinamide analogs & derivatives, Niacinamide pharmacology, Phenylurea Compounds pharmacology, Proto-Oncogene Proteins c-myc metabolism, Sorafenib, Carcinoma, Hepatocellular pathology, Cell Movement drug effects, Cell Proliferation drug effects, Disease Models, Animal, Liver Neoplasms pathology, Myeloid Cells pathology
- Abstract
Background & Aims: Myeloid derived suppressor cells (MDSC) are immature myeloid cells with immunosuppressive activity. They accumulate in tumor-bearing mice and humans with different types of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the biology of MDSC in murine HCC models and to identify a model, which mimics the human disease., Methods: The comparative analysis of MDSC was performed in mice, bearing transplantable, diethylnitrosoamine (DEN)-induced and MYC-expressing HCC at different ages., Results: An accumulation of MDSC was found in mice with HCC irrespective of the model tested. Transplantable tumors rapidly induced systemic recruitment of MDSC, in contrast to slow-growing DEN-induced or MYC-expressing HCC, where MDSC numbers only increased intra-hepatically in mice with advanced tumors. MDSC derived from mice with subcutaneous tumors were more suppressive than those from mice with DEN-induced HCC. Enhanced expression of genes associated with MDSC generation (GM-CSF, VEGF, IL6, IL1β) and migration (MCP-1, KC, S100A8, S100A9) was observed in mice with subcutaneous tumors. In contrast, only KC levels increased in mice with DEN-induced HCC. Both KC and GM-CSF overexpression or anti-KC and anti-GM-CSF treatment controlled MDSC frequency in mice with HCC. Finally, the frequency of MDSC decreased upon successful anti-tumor treatment with sorafenib., Conclusions: Our data indicate that MDSC accumulation is a late event during hepatocarcinogenesis and differs significantly depending on the tumor model studied., (Published by Elsevier B.V.)
- Published
- 2013
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14. Evaluation of early cerebral metabolic, perfusion and microstructural changes in HCV-positive patients: a pilot study.
- Author
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Bladowska J, Zimny A, Knysz B, Małyszczak K, Kołtowska A, Szewczyk P, Gąsiorowski J, Furdal M, and Sąsiadek MJ
- Subjects
- Adult, Aspartic Acid analogs & derivatives, Aspartic Acid metabolism, Blood Volume, Brain blood supply, Brain Diseases etiology, Brain Diseases metabolism, Brain Diseases pathology, Case-Control Studies, Cerebrovascular Circulation, Choline metabolism, Creatine metabolism, Diffusion Tensor Imaging, Female, Hepatitis C, Chronic complications, Humans, Magnetic Resonance Angiography, Magnetic Resonance Spectroscopy, Male, Middle Aged, Pilot Projects, Tissue Distribution, Young Adult, Brain metabolism, Brain pathology, Hepatitis C, Chronic metabolism, Hepatitis C, Chronic pathology
- Abstract
Background & Aims: The aim of the study was to evaluate early metabolic perfusion, and microstructural cerebral changes in patients with the hepatitis C virus (HCV) infection and normal appearing brain on plain MR using advanced MR techniques, as well as to assess correlations of MR measurements with the liver histology activity index (HAI)., Methods: Fifteen HCV-positive patients and 18 control subjects underwent single voxel MR spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI), using a 1.5T MR unit. MRS metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr) were calculated. PWI values of relative cerebral blood volume (rCBV) were assessed from 8 areas including several cortical locations, basal ganglia, and fronto-parietal white matter. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts., Results: Compared to controls, HCV-positive patients showed significantly (p < 0.05) lower NAA/Cr ratios within frontal and parietal white matters, lower rCBV values within frontal and temporo-parietal cortices, decreased FA values, as well as increased ADC values in several white matter tracts. We also found elevated rCBV values in basal ganglia regions. The increase in mI/Cr and Cho/Cr ratio was correlated with a higher HAI score., Conclusions: The results of advanced MR techniques indicate neurotoxicity of HCV reflected by neuronal impairment within white matter, cortical hypoperfusion, and disintegrity within several white matter tracts. Hyperperfusion in basal ganglia may be an indicator of brain inflammation in HCV patients. Our findings may suggest a biologic link between HCV-related liver disease and cerebral dysfunction., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2013
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15. Suppression of lithium chloride-induced conditioned gaping (a model of nausea-induced behaviour) in rats (using the taste reactivity test) with metoclopramide is enhanced by cannabidiolic acid.
- Author
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Rock EM and Parker LA
- Subjects
- Animals, Male, Nausea prevention & control, Rats, Rats, Sprague-Dawley, Antiemetics pharmacology, Cannabinoids pharmacology, Conditioning, Psychological drug effects, Lithium Chloride pharmacology, Metoclopramide pharmacology, Nausea chemically induced, Taste drug effects
- Abstract
We aimed to determine the potential of various doses of metoclopramide (MCP, a dopamine antagonist) to reduce lithium chloride (LiCl)-induced conditioned gaping (a nausea-induced behaviour) in rats, using the taste reactivity test. We then evaluated whether an ineffective low dose of cannabidiolic acid (CBDA, 0.1 μg/kg, Rock and Parker, 2013), the potent acidic precursor of cannabidiol (CBD, a non-psychoactive component of cannabis) could enhance the anti-nausea effects of an ineffective low dose of MCP. MCP (3.0 mg/kg) reduced conditioned gaping responses. Coadministration of ineffective doses of MCP (0.3 mg/kg) and CBDA (0.1 μg/kg) enhanced the suppression of conditioned gaping, over that of either drug alone, without interfering with conditioned taste avoidance. MCP dose-dependently reduced nausea-induced conditioned gaping in rats. As well, the suppression of conditioned gaping was enhanced when ineffective doses of MCP and CBDA were coadministered. These data suggest that CBDA could be a powerful adjunct treatment to anti-emetic regimens for chemotherapy-induced nausea., (© 2013.)
- Published
- 2013
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16. CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues.
- Author
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Fujii M, Inoguchi T, Batchuluun B, Sugiyama N, Kobayashi K, Sonoda N, and Takayanagi R
- Subjects
- Adipose Tissue pathology, Animals, CTLA-4 Antigen immunology, Cell Polarity, Macrophages pathology, Male, Mice, Mice, Inbred C57BL, Obesity pathology, Adipose Tissue immunology, CTLA-4 Antigen therapeutic use, Immunotherapy methods, Insulin Resistance immunology, Macrophages immunology, Obesity immunology, Obesity therapy
- Abstract
It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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17. Flow cytometry and gene expression profiling of immune cells of the carotid plaque and peripheral blood.
- Author
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Sternberg Z, Ghanim H, Gillotti KM, Tario JD Jr, Munschauer F, Curl R, Noor S, Yu J, Ambrus JL Sr, Wallace P, and Dandona P
- Subjects
- Aged, Aged, 80 and over, B-Lymphocytes cytology, B-Lymphocytes immunology, Cell Adhesion immunology, Female, Flow Cytometry, Humans, Immunomagnetic Separation, Immunophenotyping, Male, Middle Aged, Monocytes cytology, Monocytes immunology, T-Lymphocytes cytology, T-Lymphocytes immunology, Thrombosis genetics, Thrombosis immunology, Thrombosis pathology, Carotid Stenosis genetics, Carotid Stenosis immunology, Carotid Stenosis pathology, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear immunology, Transcriptome immunology, Vasculitis genetics, Vasculitis immunology, Vasculitis pathology
- Abstract
Objectives: The relative contribution of the local vs. peripheral inflammation to the atherothrombotic processes is unknown. We compared the inflammatory status of the immune cells of the carotid plaque with similar cells in peripheral circulation of patients with advanced carotid disease (PCDs)., Methods: Mononuclear cells (MNCs) were extracted from carotid endarterectomy (CEA) samples by enzymatic digestion and subsequent magnetic cell sorting. The cell surface antigenic expressions, and mRNA expression levels were compared between CEA MNCs and peripheral MNCs, using flow cytometry and RT-PCR techniques., Results: The percentages of resting MNCs were lower, and activated MNCs, particularly monocytes, were higher in the CEAMNCs, as compared to the peripheral MNCs. The percentages of activated T cells and B cells were higher in the peripheral MNCs of PCDs, than in healthy controls (HCs), but the percentages of activated monocytes did not differ between the two groups. The expression levels of both pro-inflammatory/pro-thrombotic (P(38), JNKB-1, Egr-1 PAI-1, MCP-1, TF, MMP-9, HMGB-1, TNF-α, mTOR) and anti-inflammatory (PPAR-γ, TGF-β) mediators were significantly higher in the CEA MNCs as compared to the peripheral MNCs. Furthermore, MMP-9 and PPAR-γ expression levels were higher in the peripheral MNCs of PCDs than HCs., Conclusion: The inflammatory status is higher in the immune cells of the carotid plaque, as compared to those cells in the peripheral blood. The altered expression levels of both pro-inflammatory/pro-thrombotic and anti-inflammatory mediators in the milieu of the plaque suggest that the balance between these various mediators may play a key role in carotid disease progression., (Published by Elsevier Ireland Ltd.)
- Published
- 2013
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