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Preferential Localization (preferential + localization)
Selected AbstractsCharacteristic 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] Temperature-dependent localization of GPI-anchored intestinal alkaline phosphatase in model rafts,JOURNAL OF MOLECULAR RECOGNITION, Issue 6 2007Marie-Cécile Giocondi Abstract In plasma membranes, most of glycosylphosphatidylinositol (GPI)-anchored proteins would be associated with rafts, a category of ordered microdomains enriched in sphingolipids and cholesterol (Ch). They would be also concentrated in the detergent resistant membranes (DRMs), a plasma membrane fraction extracted at low temperature. Preferential localization of GPI-anchored proteins in these membrane domains is essentially governed by their high lipid order, as compared to their environment. Changes in the temperature are expected to modify the membrane lipid order, suggesting that they could affect the distribution of GPI-anchored proteins between membrane domains. Validity of this hypothesis was examined by investigating the temperature-dependent localization of the GPI-anchored bovine intestinal alkaline phophatase (BIAP) into model raft made of palmitoyloleoylphosphatidylcholine/sphingomyelin/cholesterol (POPC/SM/Chl) supported membranes. Atomic force microscopy (AFM) shows that the inserted BIAP is localized in the SM/Chl enriched ordered domains at low temperature. Above 30°C, BIAP redistributes and is present in both the ,fluid' POPC enriched and the ordered SM/Chl domains. These data strongly suggest that in cells the composition of plasma membrane domains at low temperature differs from that at physiological temperature. Copyright © 2007 John Wiley & Sons, Ltd. [source] Preferential localization of recombinant factor VIIa to platelets activated with a combination of thrombin and a glycoprotein VI receptor agonistJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007M. KJALKE Summary., Background:, Activation of platelets with a combination of collagen and thrombin generates a subpopulation of highly procoagulant ,coated' platelets characterized by high surface expression of fibrinogen and other procoagulant proteins. Objectives:, To analyze the interaction of recombinant factor VIIa (rFVIIa) with coated platelets. Methods and results:, rFVIIa localized to the coated platelets in flow cytometry experiments, while minimal rFVIIa was found on platelets activated with adenosine diphosphate, thrombin or via glycoprotein VI individually, and essentially no rFVIIa was found on non-stimulated platelets. Removal of the , -carboxyglutamic acid (Gla) domain of rFVIIa, and addition of EDTA, annexin V or excess prothrombin inhibited rFVIIa localization to the coated platelets, indicating that the interaction was mediated by the calcium-dependent conformation of the Gla domain and platelet exposure of negatively charged phospholipids. A reduced level of platelet fibrinogen exposure was observed at hemophilia A-like conditions in a model system of cell-based coagulation, indicating that coated platelet formation in hemophilia may be diminished. Addition of rFVIIa dose-dependently enhanced thrombin generation and partly restored platelet fibrinogen exposure. Conclusions:, The data suggest that rFVIIa localized preferentially on platelets activated with dual agonists, thereby ensuring enhanced thrombin generation localized at the site of injury where both collagen and tissue factor are exposed, the latter ensuring the formation of thrombin necessary for coated platelet formation. [source] Nutritional channels in breast cancerJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Alejandro Godoy Abstract Breast cancers increase glucose uptake by increasing expression of the facilitative glucose transporters (GLUTs), mainly GLUT1. However, little is known about the relationship between GLUT1 expression and malignant potential in breast cancer. In this study, expression and subcellular localization of GLUT1 was analysed in vivo in breast cancer tissue specimens with differing malignant potential, based on the Scarff-Bloom-Richardson (SBRI, II, III) histological grading system, and in vitro in the breast cancer cell lines, MDA-MB-468 and MCF-7, and in MDA-MB-468 cells grown as xenografts in nude athymic BALB/c male mice. In situ hybridization analyses demonstrated similar levels of GLUT1 mRNA expression in tissue sections from breast cancers of all histological grades. However, GLUT1 protein was expressed at higher levels in grade SBRII cancer, compared with SBRI and SBRIII, and associated with the expression of the proliferation marker PCNA. Immunolocalization analyses in SBRII cancers demonstrated a preferential localization of GLUT1 to the portions of the cellular membrane that faced neighbouring cells and formed ,canaliculi-like structures', that we hypothesize could have a potential role as ,nutritional channels'. A similar pattern of GLUT1 localization was observed in confluent cultures of MDA-MB-468 and MCF-7, and in MDA-MB-468 cells grown as xenografts, but not in the normal breast epithelial cell line HMEC. However, no relationship between GLUT1 expression and malignant potential of human breast cancer was observed. Preferential subcellular localization of GLUT1 could represent a physiological adaptation of a subset of breast cancer cells that form infiltrative tumours with a nodular growth pattern and that therefore need a major diffusion of glucose from blood vessels. [source] Identification of the isoforms of Ca2+/calmodulin-dependent protein kinase II and expression of brain-derived neurotrophic factor mRNAs in the substantia nigraJOURNAL OF NEUROCHEMISTRY, Issue 1 2006Akifumi Kamata Abstract Ca2+/calmodulin-dependent protein kinase (CaMK)II is highly expressed in the CNS and mediates activity-dependent neuronal plasticity. Four CaMKII isoforms, ,, ,, , and ,, have a large number of splicing variants. Here we identified isoforms of CaMKII in the rat substantia nigra (SN). Northern blot and RT,PCR analyses revealed that the , and , isoform mRNAs with several splicing variants were predominantly expressed in SN. Immunoblot analysis indicated that the major isoforms were ,A, ,C, ,1 and ,3. An immunohistochemical study also confirmed the preferential localization of , and , isoforms in SN dopaminergic neurons. In dopaminergic neurons, immunoreactivity against anti-CaMKII,1,4 antibody was detected in both nucleus and cytoplasm, in contrast to the predominant expression of , isoforms in the cytoplasm. Furthermore, we showed expression of brain-derived neurotrophic factor (BDNF) mRNAs with exons II and IV in SN. Taken together with our previous observations, the results suggest that the CaMKII,3 isoform is involved in the expression of BDNF in the SN. [source] A Novel Micellar PEGylated Hyperbranched Polyester as a Prospective Drug Delivery System for PaclitaxelMACROMOLECULAR BIOSCIENCE, Issue 9 2008Christina Kontoyianni Abstract A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aqueous solutions of BH40-PEG of 10, 30, 60, and 90 mg,·,mL,1, respectively. More than 50% of the drug is released at a steady rate and release is almost complete within 10 h. The toxicity of BH40-PEG was assessed in vitro with A549 human lung carcinoma cells and found to be nontoxic for 3 h incubation up to a 1.75 mg,·,mL,1 concentration while LD50 was 3.5 mg,·,mL,1. Finally, it was efficiently internalized in cells, primarily in the absence of foetal bovine serum, while confocal microscopy revealed the preferential localization of the compound in cell nuclei. [source] Studies on nylon-6/EVOH/clay ternary compositesPOLYMER COMPOSITES, Issue 1 2006N. Artzi Nylon-6 (Ny-6)/EVOH blends are interesting host multiphase systems for incorporation of low clay contents. The Ny-6/EVOH blend is a unique system, which tends to chemically react during melt-mixing, affecting thermal, morphological and mechanical properties of the ternary systems containing clay. The addition of clay seems to interrupt the chemical reaction between the host polymers at certain compositions, leading to lower blending torque levels when clay is added. A competition between Ny-6 and EVOH regarding the intercalation process takes place. Ny-6 seems to lead to exfoliated structure, whereas EVOH forms intercalated structure, as revealed from XRD and TEM analyses, owing to thermodynamic considerations and preferential localization of the clay in Ny-6. Hence, the ternary systems have combined intercalated and delaminated morphology or complete exfoliated morphology depending on blend composition and clay content. Selective extraction experiments (gel content) indicate the formation of chemical reaction between the Ny-6 and EVOH, and give an indirect indication of the polymer content residing in the galleries. The thermal properties of the polymers were found to be affected by the occurrence of chemical reaction, the level of intercalation and exfoliation and plasticizing effect of the low molecular weight onium ions treating the clay. Of special interest is the increased storage modulus attained upon the addition of only 1.5 wt% clay. POLYM. COMPOS. 27:15,23, 2006. © 2005 Society of Plastics Engineers [source] Chromosome topology in normal and aneuploid blastomeres from human embryosPRENATAL DIAGNOSIS, Issue 12 2007Jan Diblík Abstract Objectives To find whether chromosomes 13, 16, 18, 21, 22, X and Y in blastomeres of human embryos are nonrandomly localized, whether their aneuploidy affects their localization and if eventual early inactivation of chromosome X with peripheral localization is present. Methods Relative distances from the nucleus center and edge of 1198 fluorescence in situ hybridization signals in 98 human blastomeres were measured in digital images for comparison with a mathematical model of random distribution in spherical nucleus. Results Comparison with the mathematical model revealed that localization of chromosomes 13, 16, 21, 22, X and Y in normal and aneuploid blastomeres and that of chromosome 18 in normal blastomeres was not significantly different from random distribution. Similarly, chromosome X in blastomeres with more than one X did not appear to have a preferential localization. Only chromosome 18 in aneuploid blastomeres was differently distributed (p < 0.0001) with a shift to the nuclear periphery (p = < 0.0001). Conclusions Peripheral localization of chromosome 18 in aneuploid blastomeres is related to embryo aneuploidy. Conversely, a peripheral localization of the inactive X chromosome was not found in blastomeres from 3-4 day old embryos. These results open the possibility to improve embryo selection after pre-implantation diagnosis. Copyright © 2007 John Wiley & Sons, Ltd. [source] Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNSTHE JOURNAL OF PHYSIOLOGY, Issue 10 2008Hideki Miwa The NMDA-type glutamate receptor is a heteromeric complex composed of the NR1 and at least one of the NR2 subunits. Switching from the NR2B to the NR2A subunit is thought to underlie functional alteration of the NMDA receptor during synaptic maturation, and it is generally believed that it results in preferential localization of NR2A subunits on the synaptic site and that of NR2B subunits on the extracellular site in the mature brain. It has also been proposed that activation of the NR2A and NR2B subunits results in long-term potentiation (LTP) and long-term depression (LTD), respectively. Furthermore, recent reports suggest that synaptic and extrasynaptic receptors may have distinct roles in synaptic plasticity as well as in gene expression associated with neuronal death. Here, we have investigated whether NR2B subunit-containing receptors are present and functional at mature synapses in the lateral nucleus of the amygdala (LA) and the CA1 region of the hippocampus, comparing their properties between the two brain regions. We have found, in contrast to the above hypotheses, that the NR2B subunit significantly contributes to synaptic transmission as well as LTP induction. Furthermore, its contribution is greater in the LA than in the CA1 region, and biophysical properties of NMDA receptors and the NR2B/NR2A ratio are different between the two brain regions. These results indicate that NR2B subunit-containing NMDA receptors accumulate on the synaptic site and are responsible for the unique properties of synaptic function and plasticity in the amygdala. [source] | ||||||||||||||||