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Sinusoids
Kinds of Sinusoids Selected AbstractsAltered aquaporin 9 expression and localization in human hepatocellular carcinomaHPB, Issue 1 2009Srikanth Padma Abstract Background:, In addition to the biochemical components secreted in bile, aquaporin (AQP) water channels exist in hepatocyte membranes to form conduits for water movement between the sinusoid and the bile canaliculus. The aim of the current study was to analyse AQP 9 expression and localization in human hepatocellular carcinoma (HCC) and non-tumourigenic liver (NTL) tissue from patients undergoing hepatic resection. Methods:, Archived tissue from 17 patients was sectioned and analysis performed using an antibody raised against AQP 9. Slides were blind-scored to determine AQP 9 distribution within HCC and NTL tissue. Results:, Aquaporin 9 was predominantly expressed in the membranes of hepatocytes and demonstrated zonal distribution relative to hepatic sinusoid structure in normal liver. In HCC arising in the absence of cirrhosis AQP 9 remained membrane-localized with zonal distribution in the majority of NTL. By contrast, AQP 9 expression was significantly decreased in the HCC mass vs. pair-matched NTL. In HCC in the presence of cirrhosis, NTL was characterized by extensive AQP 9 staining in the membrane in the absence of zonal distribution and AQP 9 staining in NTL was significantly greater than that observed in the tumour mass. Conclusions:, These data demonstrate that human HCC is characterized by altered AQP 9 expression and AQP 9 localization in the NTL mass is dependent on underlying liver pathology. Given the central role of AQPs in normal liver function and the potential role of AQPs during transformation and progression, these data may prove valuable in future diagnostic and/or therapeutic strategies. [source] On parameter estimation of a simple real-time flow aggregation modelINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 7 2006Huirong Fu Abstract There exists a clear need for a comprehensive framework for accurately analysing and realistically modelling the key traffic statistics that determine network performance. Recently, a novel traffic model, sinusoid with uniform noise (SUN), has been proposed, which outperforms other models in that it can simultaneously achieve tractability, parsimony, accuracy (in predicting network performance), and efficiency (in real-time capability). In this paper, we design, evaluate and compare several estimation approaches, including variance-based estimation (Var), minimum mean-square-error-based estimation (MMSE), MMSE with the constraint of variance (Var+MMSE), MMSE of autocorrelation function with the constraint of variance (Var+AutoCor+MMSE), and variance of secondary demand-based estimation (Secondary Variance), to determining the key parameters in the SUN model. Integrated with the SUN model, all the proposed methods are able to capture the basic behaviour of the aggregation reservation system and closely approximate the system performance. In addition, we find that: (1) the Var is very simple to operate and provides both upper and lower performance bounds. It can be integrated into other methods to provide very accurate approximation to the aggregation's performance and thus obtain an accurate solution; (2) Var+AutoCor+MMSE is superior to other proposed methods in the accuracy to determine system performance; and (3) Var+MMSE and Var+AutoCor+MMSE differ from the other three methods in that both adopt an experimental analysis method, which helps to improve the prediction accuracy while reducing computation complexity. Copyright © 2005 John Wiley & Sons, Ltd. [source] Mesenchymal cells in the liver , one cell type or two?LIVER INTERNATIONAL, Issue 4 2002G. Ramadori Abstract: The wall of the liver sinusoid is made of highly specialized cells, the hepatic stellate cells (HSC) which together with the sinusoidal endothelial cells represent a loose barrier to the corpusculate part of the blood flowing through the liver. Quiescent stellate cells (quiescent HSC) store Vitamin A; "activated" stellate cells become involved in the reaction to acute or chronic noxae damaging the liver parenchyma. Activated HSC show increased protein synthesis capacity, increased DNA-synthesis and acquire a myofibroblast-like phenotype. Under similar conditions liver myofibroblasts (MF) of the portal field and of the pericentral area may also become "activated" by increasing protein synthesis, DNA synthesis and cell division. They express the fibulin-2 gene and produce large amounts of IL-6. In contrast to "activated" HSC they do not undergo spontaneous apoptosis in vitro and do not express the CD95-ligand gene. So far no definite prove has been found for a "transdifferentiation" of HSC to myofibroblasts. On the contrary an increasing amount of data support the conviction that HSC and MF represent two similar but not identical cell populations the latter being comparable to those of other organs. [source] Universal fitting formulae for baryon oscillation surveysMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2006Chris Blake ABSTRACT The next generation of galaxy surveys will attempt to measure the baryon oscillations in the clustering power spectrum with high accuracy. These oscillations encode a preferred scale which may be used as a standard ruler to constrain cosmological parameters and dark energy models. In this paper we present simple analytical fitting formulae for the accuracy with which the preferred scale may be determined in the tangential and radial directions by future spectroscopic and photometric galaxy redshift surveys. We express these accuracies as a function of survey parameters such as the central redshift, volume, galaxy number density and (where applicable) photometric redshift error. These fitting formulae should greatly increase the efficiency of optimizing future surveys, which requires analysis of a potentially vast number of survey configurations and cosmological models. The formulae are calibrated using a grid of Monte Carlo simulations, which are analysed by dividing out the overall shape of the power spectrum before fitting a simple decaying sinusoid to the oscillations. The fitting formulae reproduce the simulation results with a fractional scatter of 7 per cent (10 per cent) in the tangential (radial) directions over a wide range of input parameters. We also indicate how sparse-sampling strategies may enhance the effective survey area if the sampling scale is much smaller than the projected baryon oscillation scale. [source] Over-Expression of Neuropeptide Urocortin and Its Receptors in Human Allergic Nasal Mucosa,THE LARYNGOSCOPE, Issue 9 2007Tae Hoon Kim MD Abstract Objectives: Urocortin (UCN) is a member of the corticotropin releasing factor (CRF) neuropeptide family. UCN act as locally expressed proinflammatory factor and induce mast cell degranulation, cytokine secretion, and trigger vascular permeability, which are mediated by CRF receptors in peripheral tissues. Considering its functional roles, UCN and its receptors may play a role in the pathogenesis of allergic nasal mucosa. Therefore, we investigated the expression profile and distribution of UCN and CRF receptors in normal and allergic nasal mucosa. Methods: Reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blotting were applied to the normal and allergic nasal mucosa. Results: The expression levels of UCN and CRF receptors were increased in allergic nasal mucosa in comparison with normal nasal mucosa. In normal nasal mucosa, UCN and CRF receptors were restricted to the vascular endothelium of submucosal cavernous sinusoids where faint staining was found. However, in allergic nasal mucosa, UCN was expressed in small vessels distributed in lamina propria and the vascular endothelium of cavernous sinusoid located in submucosa. Many scattered positive cells were also found in allergic nasal mucosa, probably UCN-positive leukocytes. CRF receptors were also localized in the vascular endothelium of small vessels and cavernous sinusoid. Conclusions: These results indicate that UCN may play a role in the regulation of vascular swelling in normal nasal mucosa. Moreover, in allergic nasal mucosa, increased expression levels of UCN and its receptors may contribute to increased mucosal swelling and vascular permeability, playing an important role in the pathogenesis of allergic rhinitis. [source] Mixtures of hemoglobin-based oxygen carriers and perfluorocarbons exhibit a synergistic effect in oxygenating hepatic hollow fiber bioreactorsBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2010Guo Chen Abstract Hepatic hollow fiber (HF) bioreactors are being developed for use as bioartificial liver assist devices (BLADs). In general, BLADs suffer from O2 limited transport, which reduces their performance. This modeling study seeks to investigate if O2 carrying solutions consisting of mixtures of hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbons (PFCs) can enhance O2 transport to hepatocytes cultured in the extra capillary space (ECS) of HF bioreactors. We simulated supplementing the circulating cell culture media stream of the HF bioreactor with a mixture containing these two types of oxygen carriers (HBOCs and PFCs). A mathematical model was developed based on the dimensions and physical characteristics of a commercial HF bioreactor. The resulting set of partial differential equations, which describes fluid transport; as well as, mass transport of dissolved O2 in the pseudo-homogeneous PFC/water phase and oxygenated HBOC, was solved to yield the O2 concentration field in the three HF domains (lumen, membrane and ECS). Our results show that mixtures of HBOC and PFC display a synergistic effect in oxygenating the ECS. Therefore, the presence of both HBOC and PFC in the circulating cell culture media dramatically improves transport of O2 to cultured hepatocytes. Moreover, the in vivo O2 spectrum in a liver sinusoid can be recapitulated by supplementing the HF bioreactor with a mixture of HBOCs and PFCs at an inlet pO2 of 80,mmHg. Therefore, we expect that PFC-based oxygen carriers will be more efficient at transporting O2 at higher O2 levels (e.g., at an inlet pO2 of 760,mmHg, which corresponds to pure O2 in equilibrium with aqueous cell culture media at 1,atm). Biotechnol. Bioeng. 2010; 105: 534,542. © 2009 Wiley Periodicals, Inc. [source] Laser-guided direct writing for three-dimensional tissue engineeringBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2005Yaakov Nahmias Abstract One of the principal limitations to the size of an engineered tissue is oxygen and nutrient transport. Lacking a vascular bed, cells embedded in an engineered tissue will consume all available oxygen within hours while out branching blood vessels will take days to vascularize the implanted tissue. One possible solution is to directly write vascular structures within the engineered tissue prior to implantation, reconstructing the tissue according to its native architecture. The cell patterning technique, laser-guided direct writing (LGDW), can pattern multiple cells types with micrometer resolution on arbitrary surfaces, including biological gels. Here we show that LGDW can pattern human umbilical vein endothelial cells (HUVEC) in two- and three-dimensions with micrometer accuracy. By patterning HUVEC on Matrigel, we can direct their self-assembly into vascular structures along the desired pattern. Finally, co-culturing the vascular structures with hepatocytes resulted in an aggregated tubular structure similar in organization to a hepatic sinusoid. This capability can facilitate studies of tissue architecture at the single cell level, and of heterotypic interactions underlying processes such as liver and pancreas morphogenesis, differentiation, and angiogenesis. Copyright © 2005 Wiley Periodicals, Inc. [source] Liver invasion by malarial parasites , how do malarial parasites break through the host barrier?CELLULAR MICROBIOLOGY, Issue 12 2004Masao Yuda Summary Malarial transmission to the human host is established by sporozoite infection of the liver. Sporozoites are released from the mosquito salivary glands and carried by the blood flow to the liver sinusoid. In the sinusoid, sporozoites leave the blood circulation by crossing the sinusoidal cell layer to infect hepatocytes, the site for their development into the erythrocyte-invasive forms. Traversal of the sinusoidal cell layer and subsequent hepatocyte infection are the most important events in sporozoite liver invasion, but the molecular basis of both events remains to be elucidated. The present review of sporozoite liver invasion focuses on recent advances in this topic obtained by application of reverse genetics. Sporozoites traverse host cells, rupturing the host cell membrane in the process. Three microneme proteins have important roles in this motility. Disruption of one of these genes abolishes or severely impairs cell traversal without affecting other types of invasive motility. Studies using these disruptant parasites indicate that cell-traversal ability is required for crossing the sinusoidal cell layer and accessing the hepatocytes for infection. This process is homologous to midgut epithelium penetration by the malarial ookinete, because identical or paralogous genes are critically involved in both processes. After arrival at the hepatocyte, the invasion mode of the sporozoites switches from cell traversal to hepatocyte infection. [source] Left Ventricular Non Compaction in ChildrenCONGENITAL HEART DISEASE, Issue 5 2010Sara H. Weisz MD ABSTRACT Left ventricular non compaction (LVNC) is a myocardial disease characterized by a hypertrabeculated myocardium. The hypertrabeculations in the left ventricular wall define deep recesses communicating with the left ventricular chamber where blood penetrates with increased risk of blood clots in the meshwork of the prominent trabeculations. The left ventricular apex and the free wall are particularly affected. During in utero ventriculogenesis, myocardial blood supply is initially linked to the presence of sinusoids, in which blood penetrates and diffuses nutriments and oxygen to myocardial cells. Progressively, with the development of the heart and the increase of cells demand of blood, coronary arteries system develops. This step is associated with myocardial modification that leads to compaction of hypertrabeculated myocardial net. Probably, the premature interruption of this process leads to ventricular noncompaction. Many studies have been conducted in adults with hypertrabeculated myocardium. To date, data regarding childhood LVNC are sparse. The aim of this review is to summarize the clinical and preclinical knowledge about LVNC in children. [source] Development of murine hepatic sinusoidal endothelial cells characterized by the expression of hyaluronan receptorsDEVELOPMENTAL DYNAMICS, Issue 8 2007Hidenori Nonaka Abstract Endothelial cells (ECs) display distinct structural and functional characteristics depending on the tissue and developmental stage; however, the development of tissue-specific ECs remains poorly understood. Here, we describe the development of hepatic sinusoids in mice based on the expression of hyaluronan receptors Stab2 and Lyve-1. Flk-1+ cells in and around the liver bud begin to express Stab2 at embryonic day (E) 9.5, before the formation of vascular lumen. Hepatic sinusoidal endothelial cells (HSECs) begin to express Lyve-1 at E10.5, and both markers continue to be expressed in HSECs thereafter. Although HSECs and lymphatic ECs (LECs) are known to share functional and phenotypic characteristics, we clearly show that HSECs can be distinguished from LECs by the expression of molecular markers and higher endocytotic activity. Our results provide new insight into the development of tissue-specific ECs and phenotypic criteria to distinguish HSECs from other types of ECs, including LECs. Developmental Dynamics 236:2258,2267, 2007. © 2007 Wiley-Liss, Inc. [source] Contribution of mesothelium-derived cells to liver sinusoids in avian embryosDEVELOPMENTAL DYNAMICS, Issue 3 2004J.M. Pérez-Pomares Abstract The developing liver is vascularized through a complex process of vasculogenesis that leads to the differentiation of the sinusoids. The main structural elements of the sinusoidal wall are endothelial and stellate (Ito) cells. We have studied the differentiation of the hepatic sinusoids in avian embryos through confocal colocalization of differentiation markers, in ovo direct labeling of the liver mesothelium, induced invasion of the developing chick liver by quail proepicardial cells, and in vitro culture of chimeric aggregates. Our results show that liver mesothelial cells give rise to mesenchymal cells which intermingle between the growing hepatoblast cords and become incorporated to the sinusoidal wall, contributing to both endothelial and stellate cell populations. We have also shown that the proepicardium, a mesothelial tissue anatomically continuous with liver mesothelium, is able to form sinusoid-like vessels into the hepatic primordium as well as in cultured aggregates of hepatoblasts. Thus, both intrinsic or extrinsic mesothelium-derived cells have the developmental potential to contribute to the establishment of liver sinusoids. Developmental Dynamics 229:465,474, 2004. © 2004 Wiley-Liss, Inc. [source] Sinusoidal modeling applied to spatially variant tropospheric ozone air pollutionENVIRONMETRICS, Issue 6 2008Nicholas Z. Muller Abstract This paper demonstrates how parsimonious models of sinusoidal functions can be used to fit spatially variant time series in which there is considerable variation of a periodic type. A typical shortcoming of such tools relates to the difficulty in capturing idiosyncratic variation in periodic models. The strategy developed here addresses this deficiency. While previous work has sought to overcome the shortcoming by augmenting sinusoids with other techniques, the present approach employs station-specific sinusoids to supplement a common regional component, which succeeds in capturing local idiosyncratic behavior in a parsimonious manner. The experiments conducted herein reveal that a semi-parametric approach enables such models to fit spatially varying time series with periodic behavior in a remarkably tight fashion. The methods are applied to a panel data set consisting of hourly air pollution measurements. The augmented sinusoidal models produce an excellent fit to these data at three different levels of spatial detail. Copyright © 2007 John Wiley & Sons, Ltd. [source] Enhancement of steady-state auditory evoked magnetic fields in tinnitusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2004Eugen Diesch Abstract The steady-state auditory evoked magnetic field and the Pbm, the magnetic counterpart of the second frontocentrally positive middle latency component of the transitory auditory evoked potential, were measured in ten tinnitus patients using a 122-channel gradiometer system. The patients had varying degrees of hearing loss. In all patients, the tinnitus frequency was located above the frequency of the audiometric edge, i.e. the location on the frequency axis above which hearing loss increases more rapidly. Stimuli were amplitude-modulated sinusoids with carrier frequencies at the tinnitus frequency, the audiometric edge, two frequencies below the audiometric edge, and two frequencies between the audiometric edge and the tinnitus frequency. Below the audiometric edge, the root-mean-square field amplitude of the steady-state response computed across the whole head as well as the contralateral and the ipsilateral dipole moment decreased as a function of carrier frequency. With carrier frequency above the audiometric edge, the steady-state response increased again. The amplitudes of the transitory Pbm component were patterned in a qualitatively similar way, but without the differences being significant. For the steady-state response, both whole-head root-mean-square field amplitude and the dipole moment of the sources at the tinnitus frequency showed significant positive correlations with subjective ratings of tinnitus intensity and intrusiveness. These correlations remained significant when the influence of hearing loss was partialled out. The observed steady-state response amplitude pattern likely reflects an enhanced state of excitability of the frequency region in primary auditory cortex above the audiometric edge. The relationship of tinnitus to auditory cortex hyperexcitability and its independence of hearing loss is discussed with reference to loss of surround inhibition in and map reorganization of primary auditory cortex. [source] Molecular characterization of the vascular features of focal nodular hyperplasia and hepatocellular adenoma: A role for angiopoietin-1,HEPATOLOGY, Issue 2 2010Annette S. H. Gouw Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are two hepatic nodular lesions of different etiologies. FNH, a polyclonal lesion, is assumed to be a regenerative reaction following a vascular injury, whereas HCA is a monoclonal, benign neoplastic lesion. In addition to features that are predominantly found in either FNH or HCA (e.g., dystrophic vessels in FNH and single arteries in HCA), FNH and HCA share morphological vascular abnormalities such as dilated sinusoids. We hypothesized that these anomalous vascular features are associated with altered expression of growth factors involved in vascular remodeling. This was based on reports of morphologically abnormal hepatic vasculature and nodular lesions in transgenic models of hepatocytic overexpression of angiopoietin-1 (Ang-1), a member of the angiopoietin family, which is crucially involved in vascular morphogenesis and homeostasis. We investigated gene and protein expression of members of the angiopoietin system and vascular endothelial growth factor A (VEGF-A) and its receptors in 9 FNH samples, 13 HCA samples, and 9 histologically normal livers. In comparison with normal samples, a significant increase in Ang-1 was found in FNH (P < 0.01) and HCA (P < 0.05), whereas no significant changes in Ang-2, receptor tyrosine kinase with immunoglobulin-like and EGF-like domains 2, VEGF-A, or vascular endothelial growth factor receptor 2 (VEGFR-2) were observed. Conclusion: Because of the different etiological contexts of a preceding vascular injury in FNH and a neoplastic growth in HCA, Ang-1 might exert different effects on the vasculature in these lesions. In FNH, it could predominantly stimulate recruitment of myofibroblasts and result in dystrophic vessels, whereas in HCA, it may drive vascular remodeling that produces enlarged vessels and arterial sprouting that generates single arteries. Hepatology 2010 [source] Induction of cellular resistance against Kupffer cell,derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioningHEPATOLOGY, Issue 2 2003Rolf J. Schauer Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H2O2. Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H2O2 (0.5 mmol/L). IP-mediated resistance against H2O2 could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H2O2 resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H2O2. Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H2O2 resistance in preconditioned livers. [source] Pathophysiologic importance of E- and L-selectin for neutrophil-induced liver injury during endotoxemia in miceHEPATOLOGY, Issue 5 2000Judy A. Lawson Neutrophils can cause parenchymal cell injury in the liver during ischemia-reperfusion and endotoxemia. Neutrophils relevant for the injury accumulate in sinusoids, transmigrate, and adhere to hepatocytes. To investigate the role of E- and L-selectin in this process, C3Heb/FeJ mice were treated with 700 mg/kg galactosamine and 100 ,g/kg endotoxin (Gal/ET). Immunogold labeling verified the expression of E-selectin on sinusoidal endothelial cells 4 hours after Gal/ET injection. In addition, Gal/ET caused up-regulation of Mac-1 (CD11b/CD18) and shedding of L-selectin from circulating neutrophils. Gal/ET induced hepatic neutrophil accumulation (422 ± 32 polymorphonuclear leukocytes [PMN]/50 high power fields [HPF]) and severe liver injury (plasma alanine transaminase [ALT] activities: 4,120 ± 960 U/L; necrosis: 44 ± 3%) at 7 hours. Treatment with an anti,E-selectin antibody (3 mg/kg, intravenously) at the time of Gal/ET administration did not significantly affect hepatic neutrophil accumulation and localization. However, the anti,E-selectin antibody significantly attenuated liver injury as indicated by reduced ALT levels (,84%) and 43% less necrotic hepatocytes. In contrast, animals treated with an anti,L-selectin antibody or L-selectin gene knock out mice were not protected against Gal/ET-induced liver injury. However, E-, L-, and P-selectin triple knock out mice showed significantly reduced liver injury after Gal/ET treatment as indicated by lower ALT levels (,65%) and reduced necrosis (,68%). Previous studies showed that circulating neutrophils of E-selectin,overexpressing mice are primed and activated similar to neutrophils adhering to E-selectin in vitro. Therefore, we conclude that blocking E-selectin or eliminating this gene may have protected against Gal/ET-induced liver injury in vivoby inhibiting the full activation of neutrophils during the transmigration process. [source] Characteristic appearances of the bone marrow in T-cell large granular lymphocyte leukaemiaHISTOPATHOLOGY, Issue 5 2007N Osuji Aims:, To augment the limited literature on bone marrow (BM) appearances in T-cell large granular lymphocyte (LGL) leukaemia and to identify a histological signature to aid in diagnosis of this condition. Methods and results:, A descriptive analysis of the histology of the BM in T-cell LGL leukaemia was performed (n = 38). Antibodies against CD3, CD4, CD5, CD8, CD16, CD56, CD57 and CD20 or CD79a were employed. Antibodies against CD68 (macrophages) and CD34 (sinusoids) were also included. BM was normocellular or hypercellular in the majority of cases, with interstitial lymphoid infiltration in 97%. Lymphoid nodules were present in 55% and intrasinusoidal permeation in 58%. Apoptotic figures and haemosiderin deposition were common. All cases showed trilinear haematopoiesis with normal or increased megakaryopoiesis and erythropoiesis, but normal/reduced myelopoiesis. Reticulin was increased (Grade II,III). Immunohistochemistry revealed interstitial infiltration in all cases and helped to identify lymphoid nodules in two-thirds of cases. Preferential localization of CD8+ T lymphocytes to the interstitium and CD4+ T lymphocytes to the periphery of CD20+ B-cell nodules was seen in almost 90% of cases. Conclusions:, Nodules with non-clonal B-cell centres surrounded by CD4+ cells, with interstitial CD8+ cells, are a characteristic finding in T-cell LGL leukaemia and may represent a histological signature for this condition. [source] Local control of the immune response in the liverIMMUNOLOGICAL REVIEWS, Issue 1 2000Percy A. Knolle Summary: The physiological function of the liver , such as removal of pathogens and antigens from the blood, protein synthesis and metabolism , requires an immune response that is adapted to these tasks and is locally regulated. Pathogenic microorganisms must be efficiently eliminated while the large number of antigens derived from the gastrointestinal tract must be tolerized. From experimental observations it is evident that the liver favours the induction of tolerance rather than the induction of immunity. The liver probably not only is involved in transplantation tolerance but contributes as well to tolerance to orally ingested antigens (entering the liver with portal-venous blood) and to containment of systemic immune responses (antigen from the systemic circulation entering the liver with arterial blood). This review summarizes the experimental data that shed light on the molecular mechanisms and the cell populations of the liver involved in local immune regulation in the liver. Although hepatocytes constitute the major cell population of the liver, direct interaction of hepatocytes with leukocytes in the blood is unlikely. Sinusoidal endothelial cells, which line the hepatic sinusoids and separate hepatocytes from leukocytes in the sinusoidal lumen, and Kupffer cells, the resident macrophage population of the liver, can directly interact with passenger leukocytes. In the liver, clearance of antigen from the blood occurs mainly by sinusoidal endothelial cells through very efficient receptor-mediated endocytosis. Liver sinusoidal endothelial cells constitutively express all molecules necessary for antigen presentation (CD54, CD80, CD86, MHC class I and class II and CD40) and can function as antigen-presenting cells for CD4+ and CD8+ T cells. Thus, these cells probably contribute to hepatic immune surveillance by activation of effector T cells. Antigen-specific T-cell activation is influenced by the local microenvironment. This microenvironment is characterized by the physiological presence of bacterial constituents such as endotoxin and by the local release of immunosuppressive mediators such as interleukin-10, prostaglandin E2 and transforming growth factor-b. Different hepatic cell populations may contribute in different ways to tolerance induction in the liver. In vitro experiments revealed that naive T cells are activated by resident sinusoidal endothelial cells but do not differentiate into effector T cells. These T cells show a cytokine profile and a functional phenotype that is compatible with the induction of tolerance. Besides sinusoidal endothelial cells, other cell populations of the liver, such as dendritic cells, Kupffer cells and perhaps also hepatocytes, may contribute to tolerance induction by deletion of T cells through induction of apoptosis. [source] Adaptive regulation of MIMO linear systems against unknown sinusoidal exogenous inputsINTERNATIONAL JOURNAL OF ADAPTIVE CONTROL AND SIGNAL PROCESSING, Issue 6 2009Maurizio Ficocelli Abstract This paper deals with the adaptive regulation problem in linear multi-input multi-output systems subject to unknown sinusoidal exogenous inputs, where the frequencies, amplitudes, and phases of the sinusoids are unknown and where the number of sinusoids is assumed to be known. The design of an adaptive regulator for the system under consideration is performed within a set of Q -parameterized stabilizing controllers. To facilitate the design of the adaptive regulator, triangular decoupling is introduced in part of the closed-loop system dynamics. This is achieved through the proper selection of the controller state feedback gain and the structure of the Q parameter. Regulation conditions are then presented for the case where the sinusoidal exogenous input properties are known. For the case where the sinusoidal exogenous input properties are unknown, an adaptation algorithm is proposed to tune the Q parameter in the expression of the parameterized controller. The online tuning of the Q parameter allows the controller to converge to the desired regulator. Convergence results of the adaptation algorithm are presented. A simulation example involving a retinal imaging adaptive optics system is used to illustrate the performance of the proposed adaptive system. Copyright © 2008 John Wiley & Sons, Ltd. [source] Hepatic effects of an open lung strategy and cardiac output restoration in an experimental lung injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2010M. KREDEL Background: Ventilation with high positive end-expiratory pressure (PEEP) can lead to liver dysfunction. We hypothesized that an open lung concept (OLC) using high PEEP impairs liver function and integrity dependent on the stabilization of cardiac output. Methods: Juvenile female Pietrain pigs instrumented with flow probes around the common hepatic artery and portal vein, pulmonary and hepatic vein catheters underwent a lavage-induced lung injury. Ventilation was continued with a conventional approach (CON) using pre-defined combinations of PEEP and inspiratory oxygen fraction or with an OLC using PEEP set above the lower inflection point of the lung. Volume replacement with colloids was guided to maintain cardiac output in the CON(V+) and OLC(V+) groups or acceptable blood pressure and heart rate in the OLC(V,) group. Indocyanine green plasma disappearance rate (ICG-PDR), blood gases, liver-specific serum enzymes, bilirubin, hyaluronic acid and lactate were tested. Finally, liver tissue was examined for neutrophil accumulation, TUNEL staining, caspase-3 activity and heat shock protein 70 mRNA expression. Results: Hepatic venous oxygen saturation was reduced to 18 ± 16% in the OLC(V,) group, while portal venous blood flow decreased by 45%. ICG-PDR was not reduced and serum enzymes, bilirubin and lactate were not elevated. Liver cell apoptosis was negligible. Liver sinusoids in the OLC(V+) and OLC(V,) groups showed about two- and fourfold more granulocytes than the CON(V+) group. Heat shock protein 70 tended to be higher in the OLC(V,) group. Conclusions: Open lung ventilation elicited neutrophil infiltration, but no liver dysfunction even without the stabilization of cardiac output. [source] Maternal and fetal microvasculature in sheep placenta at several stages of gestationJOURNAL OF ANATOMY, Issue 3 2010Shireen A. Hafez Abstract Maternal and fetal microvasculature was studied in ewes at days 50, 90 and 130 of gestation using microvascular corrosion casting and scanning electron microscopy. Microvascular corrosion casts of caruncles at day 50 were cup-shaped with a centrally located cavity. Branches of radial arteries entered the caruncle from its base and ramified on the maternal surface of the caruncle. Stem arteries broke into an extensive mesh of capillaries forming crypts on the fetal surface. The architecture of the caruncle at day 90 was similar to what was found at day 50 but the vascularity and the depth of the crypts increased in correspondence to increased branching of fetal villi. The substance of the caruncle was thicker at day 130 compared with day 50, with no remarkable difference compared with day 90. Capillary sinusoids of irregular form and diameter were observed on the fetal surface of the caruncle at all stages. These sinusoids may reduce blood flow resistance and subsequently increase transplacental exchange capacity. A microvascular corrosion cast of the cotyledon was cup-shaped with wide and narrow sides. Cotyledonary vessels entered and left the cotyledon from the narrow side. A cotyledonary artery gave proximal collateral branches immediately after entering the cotyledon and then further branched to supply the remaining portion of the cotyledon. Vessel branches broke into a mesh of capillaries forming the fetal vascular villi. Fetal villi that were nearest to the center of the cotyledon were the longest. Capillaries forming villi were in the form of a web-like mesh, were irregular in size and had sinusoidal dilations. The architecture of the cotyledon at day 90 was similar to day 50, but the vascularity increased. Branching of the fetal villi became more abundant. This extensive branching presumably allows a higher degree of invasion and surface contact to maternal tissues. At day 130, the distal portions of the fetal villi showed low ridges and troughs to increase the surface area for diffusion. Branching of fetal villi appears to influence the elaboration of maternal crypts in all stages of gestation. However, correspondence between crypts and villi is restricted to distal portions of fetal villi. [source] High-flow priapism complicating ischemic priapism following iatrogenic laceration of the dorsal artery during a Winter procedureJOURNAL OF CLINICAL ULTRASOUND, Issue 1 2009Michele Bertolotto Abstract We report a case of a patient who developed high-flow priapism following a Winter procedure performed for the treatment of low-flow ischemic priapism. During the creation of bilateral cavernosal,glandular shunts, the tip of the left dorsal artery was accidentally lacerated. A fistula developed through the shunt between the torn artery and the cavernosal sinusoids of the tip of the left corpus cavernosum. Gray-scale and Doppler sonography and angiography allowed diagnosis and guided the therapeutic approach. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009 [source] Hepatic arterial flow becomes the primary supply of sinusoids following partial portal vein ligation in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2006Yukihiro Yokoyama Abstract Background and Aim:, Partial portal vein ligation (PPVL) is a commonly used procedure to induce prehepatic portal hypertension in animal models. The aim of this study was to test the hypothesis that the hepatic arterial flow becomes the primary source feeding the sinusoids in the liver after PPVL. Methods:, Sprague,Dawley rats underwent either sham operation or partial portal vein ligation (PPVL). The number of vessels in the liver at 2 weeks postoperatively was determined by factor VIII immunolocalization and the gene expression of angiogenic factors was assessed by RT-PCR. The total hepatic arterial supply to the liver was measured using the fluorescent microsphere injection technique. To further test the hypothesis, two additional groups of rats underwent hepatic artery ligation (HAL) or PPVL plus HAL (PPHAL). The integrity of hepatic microcirculation was then evaluated in all four groups by intravital microscopy. Results:, At 2 weeks after operation, the number of vessels detected by factor VIII staining was significantly higher in PPVL compared to sham. Densitometric analysis of RT-PCR bands revealed a significant increase of vascular endothelial growth factor gene expression in PPVL compared to sham. Arterial flow to the liver measured by fluorescent microspheres was increased by 190% in PPVL compared to sham. When all four groups were compared, no prominent histological abnormality was observed in sham, HAL, and PPVL groups; however, PPHAL livers showed focal necrosis and inflammatory cell infiltration around the portal triads. Additionally, only the PPHAL livers showed a decreased sinusoidal diameter and significantly lower perfusion index (PPHAL 42.9 ± 6.1; sham 85.7 ± 7.0, PPVL 80.2 ± 6.5, HAL 70.9 ± 4.5). Conclusions:, These results suggest that the hepatic artery flow becomes the primary source for the blood supply of sinusoids and the compensatory change in the hepatic arterial system plays a critical role in maintaining microcirculatory perfusion following the restriction of the portal vein flow by PPVL. [source] Role of endothelin in endotoxin-induced hepatic microvascular dysfunction in rats fed chronically with ethanolJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2001Yoshinori Horie Abstract Background: We examined the role of endothelin in endotoxin-induced hepatic microcirculatory disturbance in pair-fed rats given a liquid diet containing ethanol or isocaloric control. Methods and Results: One lobe of the liver was observed with the use of an intravital microscope. Erythrocytes (RBCs) labeled with fluorescein isothiocyanate (FITC) were injected, and the flow velocity of the FITC-RBCs in the sinusoids was measured with an off-line velocimeter. The flow velocity decreased 30 min after 1 mg/kg of lipopolysaccharide (LPS) was administered to the controls, and portal pressure (PP) was increased at 60 min. In ethanol-fed rats, however, both the flow velocity and PP increased in the early phase (at 10 min), and in the late phase, flow velocity decreased and PP increased more than in the controls. The LPS-induced decrease in flow velocity was blunted, when BQ-123, an antagonist of endothelin receptor subtype A, was infused into ethanol-fed rats, and BQ-123 also attenuated the change in PP. The plasma endothelin levels in both systemic and portal blood of the ethanol-fed rats were higher than in the controls. Conclusions: These results suggest that endothelin plays a role in the LPS-induced hepatic microcirculatory disturbance, especially in alcohol-fed animals. [source] Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2000Masayuki Ohtsuka Abstract Background and Aims: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. Methods: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. Results: Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase : alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. Conclusion: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage. [source] P-selectin mediates leukocyte rolling in concanavalin-A-induced hepatitisLIVER INTERNATIONAL, Issue 5 2005Sandra March Abstract: Concanavalin- A (Con-A)-induced hepatitis is an experimental model of human autoimmune hepatitis characterized by leukocyte activation and infiltration of the liver. The aim of the present study was to evaluate the role of P-selectin on leukocyte,endothelial interactions within the hepatic microvasculature in response to Con-A. Methods: The study was performed in P-selectin-deficient mice and wild-type mice pretreated with anti-P-selectin blocking monoclonal antibody (mAb) or vehicle. After 2 h of Con-A (20 mg/kg i.v.) or PBS administration, leukocyte rolling and adhesion and the index of sinusoidal perfusion were evaluated using the intravital microscopy technique in the liver. Apoptosis was determined by flow cytometry analysis of caspase-3 activity assayed on freshly isolated hepatocytes. Results: Con-A induced a significant increase in leukocyte rolling, mainly located at the central venule (2.1±0.4 vs 0.6±0.2 cells/min in wild-type mice treated with vehicle) and less marked, but still significant, in portal venules. This was associated with a significant increase in leukocyte adhesion. In P-selectin-deficient mice treated with Con-A, leukocyte rolling in portal and central venules was markedly reduced. However, leukocyte adhesion was only partially attenuated. A few sinusoids were perfused in wild-type mice treated with Con-A (26%). The percentage of perfused sinusoids was significantly higher in P-selectin-deficient mice (45%; P<0.05 vs wild-type). Similar effects were noted after the simultaneous injection of Con-A and anti-P-selecting mAb in wild-type mice. After Con-A treatment, apoptosis was markedly reduced in isolated hepatocytes of P-selectin-deficent mice (37±7% vs 75±5% in wild type). Conclusion: The results of this intravital microscopy study clearly demonstrate that P-selectin is involved in the initial leukocyte rolling that leads to the development of Con-A-induced liver injury. [source] Morphological mechanisms for regulating blood flow through hepatic sinusoidsLIVER INTERNATIONAL, Issue 1 2000Robert S. McCuskey Abstract: This review summarizes what is known about the various morphological sites that regulate the distribution of blood flow to and from the sinusoids in the hepatic microvascular system. These sites potentially include the various segments of the afferent portal venules and hepatic arterioles, the sinusoids themselves, and central and hepatic venules. Given the paucity of smooth muscle in the walls of these vessels, various sinusoidal lining cells have been suggested to play a role in regulating the diameters of sinusoids and influencing the distribution and velocity of blood flow in these vessels. While sinusoidal endothelial cells have been demonstrated to be contractile and to exhibit sphincter function, attention has recently focused on the perisinusoidal stellate cell as the cell responsible for controlling the sinusoidal diameter. A very recent study, however, suggested that the principal site of vasoconstriction elicited by ET-1 was the pre-terminal portal venule. This raised the question of whether or not the diameters of sinusoids might decrease due to passive recoil when inflow is reduced or eliminated and intra-sinusoidal pressure falls. In more recent in vivo microscopic studies, clamping of the portal vein dramatically reduced sinusoidal blood flow as well as the diameters of sinusoids. The sinusoidal lumens rapidly returned to their initial diameters upon restoration of portal blood flow suggesting that sinusoidal blood pressure normally distends the sinusoidal wall which can recoil when the pressure drops. Stellate cells may be responsible for this reaction given the nature of their attachment to parenchymal cells by obliquely oriented microprojections from the lateral edges of their subendothelial processes. This suggests that care must be exercised when interpreting the mechanism for the reduction of sinusoidal diameters following drug administration without knowledge of changes occurring to the portal venous and hepatic inflow. [source] Effects of hyperbaric oxygen exposure on experimental hepatic ischemia reperfusion injury: Relationship between its timing and neutrophil sequestrationLIVER TRANSPLANTATION, Issue 12 2005Kenji Kihara Recent studies have shown that hyperbaric oxygen therapy (HBOT) reduces neutrophil endothelial adherence in venules and also blocks the progressive arteriolar vasoconstriction associated with ischemia-reperfusion (I-R) injury in the extremities and the brain. In order to elucidate the effects of HBOT after I-R in digestive organs, particularly in the liver, we evaluated the following: 1) the relationship between timing of HBOT and tissue damage; and 2) HBOT's effects on neutrophil sequestration. Using a hepatic I-R (45 minute) model in male rats, survival rate, liver tissue damage, and neutrophil accumulation within the sinusoids in the HBOT-treated group (Group H) were compared to those in the nontreated group (Group C). For the HBOT-treated group, HBOT was administered as 100% oxygen, at 2.5 atm absolute, for 60 minutes. When HBOT was given 30 minute after I-R, the survival rate was much better in Group H than in Group C. HBOT performed within 3 hours of I-R markedly suppressed increases in the malondialdehyde level in tissues of the liver and lessened the congestion in the sinusoids. In addition, HBOT just after I-R caused decreased number of cells stained by the naphthol AS-D chloroacetate esterase infiltrating into the sinusoids. HBOT 3 hours after reperfusion, however, showed no clear effects upon neutrophil sequestration compared to Group C. These results indicate that HBOT performed within 3 hours of I-R alleviates hepatic dysfunction and improves the survival rate after I-R. Herein, we propose 1 possible mechanism for these beneficial effects: early HBOT given before neutrophil-mediated injury phase may suppress the accumulation of neutrophils after I-R. In conclusion, we believe that the present study should lead to an improved understanding of HBOT's potential role in hepatic surgery. (Liver Transpl 2005;11:1574,1580.) [source] Capillarization of the sinusoids in liver fibrosis: Noninvasive assessment with contrast-enhanced MRI in the rabbitMAGNETIC RESONANCE IN MEDICINE, Issue 4 2003Bernard E. Van Beers Abstract Sinusoidal capillarization induces microcirculatory changes in liver cirrhosis and fibrosis. The purpose of this study was to assess whether contrast-enhanced MRI can be used to demonstrate the effects of sinusoidal capillarization in liver fibrosis. Dynamic MRI after injection of a low-molecular-weight contrast agent of 0.56 kDa (Gd-DOTA), and two high-molecular-weight contrast agents of 6.47 kDa and 52 kDa (P792 and P717) was performed in rabbits with liver fibrosis induced by cholesterol and diethylstilbestrol. The hepatic distribution volume accessible to the high-molecular-weight agents decreased in the rabbits with liver fibrosis (P792: 7.8% ± 1.7% vs. 10.1% ± 1.8% in normal rabbits, P = .038; P717: 6.2% ± 2.1% vs. 9.7% ± 1.6% in normal rabbits, P = .007), whereas the hepatic mean transit time (MTT) of the low-molecular-weight agent was increased (15.9 ± 8.0 s vs. 8.8 ± 2.6 s in normal rabbits, P = .015). In rabbits with liver fibrosis, the clearance of indocyanine green (ICG) was correlated with the volume accessible to the high-molecular-weight agents (P792: r = 0.810, P = .015; P717: r = 0.857, P = .007). The collagen content of the liver was inversely correlated with the distribution volume of P717 (r = ,.833, P = .010) and with the ICG clearance (r = ,.810, P = .015). It was concluded that the microcirculatory changes induced by sinusoidal capillarization in liver fibrosis can be demonstrated noninvasively with MRI. Magn Reson Med 49:692,699, 2003. © 2003 Wiley-Liss, Inc. [source] Platelet Recruitment in the Murine Hepatic Microvasculature During Experimental Sepsis: Role of NeutrophilsMICROCIRCULATION, Issue 2 2006GEORG SINGER ABSTRACT Objectives: Sepsis is a major clinical problem that often results in the dysfunction or failure of multiple organs, including the liver. While inflammatory cell activation has been implicated as an early critical event in sepsis-induced liver dysfunction, there is growing evidence for the involvement of activated platelets in this pathologic process. Methods: Intravital microscopy was used in this study to assess the magnitude and time course of platelet adhesion in the liver microcirculation during experimental sepsis and to determine whether the platelet accumulation is linked to leukocyte infiltration. The adhesion of platelets and leukocytes in terminal hepatic venules (THV) and sinusoids was quantified at 2, 4, and 6 h after abdominal sepsis induced by cecal ligation and puncture (CLP). Results: While the rolling and firm adhesion of platelets and leukocytes in THV were not altered in the first 2 h after CLP, platelet recruitment was observed at 4 h and further elevated at 6 h after CLP. Leukocyte adhesion in THV exhibited a similar time course. A similar accumulation of blood cells in sinusoids was noted after CLP. This was accompanied by an increased number of nonperfused sinusoids. CLP-induced leukocyte and platelet recruitment in THV and sinusoids was attenuated in mice rendered neutropenic with anti-neutrophil serum. Conclusion: These findings indicate that sepsis is associated with a neutrophil-dependent recruitment of platelets in the liver microcirculation that impairs sinusoidal perfusion and may contribute to the liver dysfunction associated with sepsis. [source] |