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Marginal Zone (marginal + zone)
Terms modified by Marginal Zone Selected AbstractsDevelopmental analysis of activin-like kinase receptor-4 (ALK4) expression in Xenopus laevisDEVELOPMENTAL DYNAMICS, Issue 2 2005Yumei Chen Abstract The type I transforming growth factor-beta (TGF,) receptor, activin-like kinase-4 (ALK4), is an important regulator of vertebrate development, with roles in mesoderm induction, primitive streak formation, gastrulation, dorsoanterior patterning, and left,right axis determination. To complement previous ALK4 functional studies, we have analyzed ALK4 expression in embryos of the frog, Xenopus laevis. Results obtained with reverse transcriptase-polymerase chain reaction indicate that ALK4 is present in both the animal and vegetal poles of blastula stage embryos and that expression levels are relatively constant amongst embryos examined at blastula, gastrula, neurula, and early tail bud stages. However, the tissue distribution of ALK4 mRNA, as assessed by whole-mount in situ hybridization, was found to change over this range of developmental stages. In the blastula stage embryo, ALK4 is detected in cells of the animal pole and the marginal zone. During gastrulation, ALK4 is detected in the outer ectoderm, involuting mesoderm, blastocoele roof, dorsal lip, and to a lesser extent, in the endoderm. At the onset of neurulation, ALK4 expression is prominent in the dorsoanterior region of the developing head, the paraxial mesoderm, and midline structures, including the prechordal plate and neural folds. Expression in older neurula stage embryos resolves to the developing brain, somites, notochord, and neural crest; thereafter, additional sites of ALK4 expression in tail bud stage embryos include the spinal cord, otic placode, developing eye, lateral plate mesoderm, branchial arches, and the bilateral heart fields. Together, these results not only reflect the multiple developmental roles that have been proposed for this TGF, receptor but also define spatiotemporal windows in which ALK4 may function to modulate fundamental embryological events. Developmental Dynamics 232:393,398, 2005. © 2004 Wiley-Liss, Inc. [source] Cortical radial glial cells in human fetuses: Depth-correlated transformation into astrocytesDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2003Leonardo C. deAzevedo Abstract In the human brain, the transformation of radial glial cells (RGC) into astrocytes has been studied only rarely. In this work, we were interested in studying the morphologic aspects underlying this transformation during the fetal/perinatal period, particularly emphasizing the region-specific glial fiber anatomy in the medial cortex. We have used carbocyanine dyes (DiI/DiA) to identify the RGC transitional forms and glial fiber morphology. Immunocytochemical markers such as vimentin and glial fibrillary acidic protein (GFAP) were also employed to label the radial cells of glial lineage and to reveal the early pattern of astrocyte distribution. Neuronal markers such as neuronal-specific nuclear protein (NeuN) and microtubule-associated protein (MAP-2) were employed to discern whether or not these radial cells could, in fact, be neurons or neuronal precursors. The main findings concern the beginning of RGC transformation showing loss of the ventricular fixation in most cases, followed by transitional figures and the appearance of mature astrocytes. In addition, diverse fiber morphology related to depth within the cortical mantle was clearly demonstrated. We concluded that during the fetal/perinatal period the cerebral cortex is undergoing the final stages of radial neuronal migration, followed by involution of RGC ventricular processes and transformation into astrocytes. None of the transitional or other radial glia were positive for neuronal markers. Furthermore, the differential morphology of RGC fibers according to depth suggests that factors may act locally in the subplate and could have a role in the process of cortical RGC transformation and astrocyte localization. The early pattern of astrocyte distribution is bilaminar, sparing the cortical plate. Few astrocytes (GFAP+) in the upper band could be found with radial processes at anytime. This suggests that astrocytes in the marginal zone could be derived from different precursors than those that differentiate from RGCs during this period. © 2003 Wiley Periodicals, Inc. J Neurobiol 55: 288,298, 2003 [source] Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2010Rogier Kersseboom Abstract B-cell receptor (BCR)-mediated signals provide the basis for B-cell differentiation in the BM and subsequently into follicular, marginal zone, or B-1 B-cell subsets. We have previously shown that B-cell-specific expression of the constitutive active E41K mutant of the BCR-associated molecule Bruton's tyrosine kinase (Btk) leads to an almost complete deletion of immature B cells in the BM. Here, we report that low-level expression of the E41K or E41K-Y223F Btk mutants was associated with reduced follicular B-cell numbers and significantly increased proportions of B-1 cells in the spleen. Crosses with 3-83,, and VH81X BCR Tg mice showed that constitutive active Btk expression did not change follicular, marginal zone, or B-1 B-cell fate choice, but resulted in selective expansion or survival of B-1 cells. Residual B cells were hyperresponsive and manifested sustained Ca2+ mobilization. They were spontaneously driven into germinal center-independent plasma cell differentiation, as evidenced by increased numbers of IgM+ plasma cells in spleen and BM and significantly elevated serum IgM. Because anti-nucleosome autoantibodies and glomerular IgM deposition were present, we conclude that constitutive Btk activation causes defective B-cell tolerance, emphasizing that Btk signals are essential for appropriate regulation of B-cell activation. [source] CD5+ B cells with the features of subepithelial B cells found in human tonsilsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Mariella Dono Abstract This study describes a CD5+ B cell that differs from the majority of the CD5+ B cells from human tonsils. This cell, isolated from in vivo activated B cells, expressed activation markers and featured a CD23,, IgMhigh, IgDlow surface phenotype, responded to T cell-independent type-2 antigens in vitro, and was detected in the subepithelial (SE) areas, the tonsil equivalent of the splenic marginal zone (MZ). Most of the cells utilized unmutated Ig VH genes, although cells with mutated genes also were found, a finding confirmed by single-cell studies. Mutated sequences were more frequent in suspensions enriched for CD27+ cells. Repeated VDJ gene sequences were observed in different molecular clones from the same cell suspension, suggesting in situ expansion. These CD5+ B cells seem to share features with previously characterized tonsil CD5, SE B cells and differ from the majority of tonsil CD5+ B cells, which have the surface phenotype of follicular mantle B cells, lack activation markers, do not respond to T cell-independent antigens, and utilize unmutated VH genes. These data are discussed considering the present views on the origin of B cell subset populations and the relationships between MZ and B1 cells. [source] Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone B cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2006Carrie Abstract B cell-activating factor belonging to the TNF family (BAFF) is a B cell survival factor required for B cell maturation. BAFF transgenic (Tg) mice develop autoimmune disorders characterized by autoantibody production, which leads to nephritis and salivary gland destruction (sialadenitis), features reminiscent of systemic lupus erythematosus and Sjögren's syndrome (SS), respectively. Disease in BAFF Tg mice correlates with the expansion of the marginal zone (MZ) B cell compartment and the abnormal presence of MZ-like B cells in the blood, LN and inflamed salivary glands, suggesting a role for these cells in BAFF-induced autoimmunity. Lymphotoxin-, (LT,)-deficient mice show disrupted splenic architecture, lack MZ B cells and some peripheral LN, and are unable to mount T cell-dependent immune responses. BAFF Tg mice lacking LT, (LT,,-BTg) retained these defects, yet still developed nephritis associated with the presence of B-1 B cells in the kidneys. However, in contrast to old BAFF Tg mice, aging LT,,-BTg mice no longer developed sialadenitis. Thus, autoimmune disorders in BAFF Tg mice are possibly events coordinated by MZ and B-1 B cells at separate anatomical sites. [source] Specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcuspneumoniae infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2005Estella Abstract The dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) homolog, SIGN-related 1 (SIGNR1) is a pathogen receptor expressed by splenic marginal zone and peritoneal macrophages, and is essential for clearance of Streptococcus pneumoniae by phagocytosis after intraperitoneal infection. Here, we identified an important in vivo function for SIGNR1 in S.pneumonia infection induced via its natural entrance route. Upon intranasal infection with S. pneumoniae, SIGNR1-deficient mice did not clear bacteria from lung and blood, and displayed severely enhanced inflammatory parameters compared to the wild-type mice. However, SIGNR1 is not expressed by alveolar macrophages, suggesting that another mechanism than a decrease in phagocytosis is responsible for this difference. Natural anti-phosphorylcholine IgM produced by marginal zone B cells is essential for protection against infection with S. pneumoniae. Strikingly, during infection, SIGNR1-deficient mice failed to produce a rapid anti-phosphorylcholine IgM response. Marginal zone macrophages have been suggested to capture antigens for presentation to marginal zone B cells. We demonstrate that marginal zone macrophages from SIGNR1-deficient mice in contrast to wild-type mice are not able to capture pneumococci from blood, suggesting that SIGNR1 on marginal zone macrophages captures S. pneumoniae for antigen presentation to and activation of marginal zone B cells, resulting in an anti-phosphorylcholine IgM response. [source] Lymphocyte-expressed BILL-cadherin/cadherin-17 contributes to the development of B cells at two stagesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005Kazuo Ohnishi Abstract The gene encoding BILL-cadherin/cadherin-17, a nonclassical cadherin expressed on B lymphocytes in a stage-and-site-specific manner, was inactivated by targeted disruption of its transmembrane/cytoplasmic portion-encoding parts. BILL-cadherin deficiency caused a threefold proB cell accumulation, as well as a reduction to half of the numbers of immature B cells in bone marrow. In spleen, CD21hiCD23lo marginal zone B cells were found reduced and the structure of the marginal zone was impaired. In addition, the size and number of germinal center as well as the number of PNA+ cells were significantly reduced in BILL-cadherin-deficient mice. In the peritoneal cavity of mutant mice IgM+Mac-1+CD5+ B1a cell, that express high BILL-cadherin in wild-type mice, was also reduced in number. The IgG1 and IgG3 antibody response to the T-independent antigen, TNP-Ficoll, was impaired in the mutant mice. These results indicate that BILL-cadherin participates in B lymphocyte development at least at two stages, first at the transition of pro/preB-I cells to preB-II cells possibly in association with surrogate light chain in bone marrow, and later at the point of development, accumulation and reactiveness of immature B cells in spleen. [source] Impaired B-1 and B-2 B,cell development and atypical splenic B,cell structures in IL-7 receptor-deficient miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Lena Erlandsson Abstract The cytokine IL-7 and its receptor are essential for normal B and T,lymphopoiesis. We have analyzed the role of this receptor in B,cell development throughout ontogeny in IL-7 receptor,,-deficient mice. We demonstrate that the IL-7 receptor becomes progressively more important with age. B,lymphopoiesis takes place, albeit at reduced levels, in fetal liver and bone marrow of young mice, but is arrested in adults. The outcome is a severe reduction, from an early age, in peripheral B,cells including follicular, marginal zone and B-1 B,cells as well as perturbed splenic B,cell structures, which are restored after adoptive transfer of normal spleen cells. We conclude that in the absence of the IL-7 receptor, the residual B,lymphopoiesis occurring early in ontogeny must be facilitated by another component, whereas the IL-7 receptor is the key factor in adults. The impairment of marginal zone and B-1 B,cells in IL-7 receptor- but not IL-7-deficient mice suggests non-redundant functions for the IL-7 receptor ligands, IL-7 and thymic stromal lymphopoietin. [source] A radialization factor in normal cortical plate restores disorganized radial glia and disrupted migration in a model of cortical dysplasiaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Thomas A. Hasling Abstract Treatment of pregnant ferrets on embryonic day 24 (E24) with the antimitotic methylazoxy methanol (MAM) leads to a specific constellation of effects in newborn kits, which include a very thin and poorly laminated neocortex, disruption of radial glial cell morphology with early differentiation into astrocytes, and abnormal positioning of Cajal,Retzius cells. We suggest that MAM treatment on E24 results in this model of cortical dysplasia by eliminating a population of cells that produce a factor capable of maintaining radial glia in their normal morphology. The abnormal radial glia, either alone or in combination with other abnormal features, are likely to prevent proper migration into the cortical plate. To test the possibility that normal cortex can provide the missing substance that influences radial glia, slices of E24 MAM-treated cortex were removed at postnatal day 0 (P0) and cultured adjacent to explants of P0 normal cortical plate. By labelling a small number of cells with injections of fluorescent dextrans into the cultured slices, we found that abnormal radial glia in MAM treated slices cocultured adjacent to normal cortical plate were restored toward normal, in comparison to E24 MAM treated slices cultured alone and in other control conditions. We also found that abnormally positioned Cajal,Retzius cells move into the marginal zone and that neurons are able to migrate into the cortical plate more effectively in the coculture condition. These data indicate that normal cortical plate of ferrets contains a factor causing radial glia to maintain their elongated morphology; the improved position of radial glia encourages repositioning of Cajal,Retzius cells and improved neuronal migration into the cortical plate. [source] Disabled-1 mRNA and protein expression in developing human cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Gundela Meyer Abstract Disabled-1 (Dab1) forms part of the Reelin,Dab1 signalling pathway that controls neuronal positioning during brain development; Dab1 deficiency gives rise to a reeler-like inversion of cortical layers. To establish a timetable of Dab1 expression in developing human brain, Dab1 mRNA and protein expression were studied in prenatal human cortex. The earliest Dab1 signal was detected at 7 gestational weeks (GW), the stage of transition from preplate to cortical plate, suggesting a role of the Reelin,Dab1 signalling pathway in preplate partition. From 12 to 20 GW, the period of maximum cortical migration, Dab1 expression was prominent in the upper tiers of the cortical plate, to decline after midgestation. Radially orientated apical dendrites of Dab1-expressing neurons indicated a predominant pyramidal phenotype. Pyramidal cells in hippocampus and entorhinal cortex displayed a more protracted time of Dab1 expression compared to neocortex. In addition, at later stages (18,25 GW), Dab1 was also expressed in large neurons scattered throughout intermediate zone and subplate. From 14 to 22 GW, particularly high levels of Dab1 mRNA and protein were observed in cells of the ventricular/subventricular zone displaying the morphology of radial glia. The partial colocalization of vimentin and Dab1 in cells of the ventricular zone supported a radial glia phenotype. The concentration of Dab1 protein in ventricular endfeet and initial portions of radial processes of ventricular-zone cells points to a possible involvement of Dab1 in neurogenesis. Furthermore, a subset of Cajal,Retzius cells in the marginal zone colocalized Dab1 and Reelin, and may thus represent a novel target of the Reelin,Dab1 signalling pathway. [source] Molecular characterization of a human scavenger receptor, human MARCOFEBS JOURNAL, Issue 3 2000Nabil A. Elshourbagy Murine MARCO has been identified recently in subsets of macrophages located in the peritoneum, marginal zone of the spleen, and the medullary cord of lymph nodes, where it has been proposed that it serves as a bacteria-binding receptor. A scavenger receptor family member with an extended collagenous domain, murine MARCO has also been demonstrated in atherosclerotic lesions of susceptible mice. We report here the identification, tissue and chromosomal localization, and pharmacological characterization of human (h)MARCO. hMARCO was identified from a macrophage cDNA library by electronic screening with the murine MARCO sequence. Nucleotide sequence analysis confirmed that the full-length hMARCO clone encoded a 519-amino acid protein sharing 68.5% identity with murine MARCO. RNA blot analysis indicated that the hMARCO transcript is 2.0 kb in length and is predominantly expressed in human lung, liver, and lymph nodes. Radiation hybrid mapping localized hMARCO to chromosome 2q14. Ligand-binding studies of COS cells expressing hMARCO demonstrated significant specific binding of both Escherichia coli and Staphylococcus aureus. In contrast, the hMARCO receptor expressed in COS cells did not specifically bind the scavenger receptor ligand acetylated low-density lipoprotein (LDL), despite its similarity to the elongated collagen-like binding domain of the macrophage scavenger receptor. In addition, acetylated (Ac)LDL and oxidized (Ox)LDL did not inhibit E. coli binding to hMARCO. These data suggest that hMARCO may play an important role in host defense, but it has no obvious role in the accumulation of modified lipoproteins during atherogenesis. [source] Geochemical weathering at the bed of Haut Glacier d'Arolla, Switzerland,a new modelHYDROLOGICAL PROCESSES, Issue 5 2002M. Tranter Waters were sampled from 17 boreholes at Haut Glacier d'Arolla during the 1993 and 1994 ablation seasons. Three types of concentrated subglacial water were identified, based on the relative proportions of Ca2+, HCO3, and SO42, to Si. Type A waters are the most solute rich and have the lowest relative proportion of Si. They are believed to form in hydrologically inefficient areas of a distributed drainage system. Most solute is obtained from coupled sulphide oxidation and carbonate dissolution (SO,CD). It is possible that there is a subglacial source of O2, perhaps from gas bubbles released during regelation, because the high SO42, levels found (up to 1200 µeq/L) are greater than could be achieved if sulphides are oxidized by oxygen in saturated water at 0 °C (c.414 µeq/L). A more likely alternative is that sulphide is oxidized by Fe3+ in anoxic environments. If this is the case, exchange reactions involving FeIII and FeII from silicates are possible. These have the potential to generate relatively high concentrations of HCO3, with respect to SO42,. Formation of secondary weathering products, such as clays, may explain the low Si concentrations of Type A waters. Type B waters were the most frequently sampled subglacial water. They are believed to be representative of waters flowing in more efficient parts of a distributed drainage system. Residence time and reaction kinetics help determine the solute composition of these waters. The initial water,rock reactions are carbonate and silicate hydrolysis, and there is exchange of divalent cations from solution for monovalent cations held on surface exchange sites. Hydrolysis is followed by SO,CD. The SO42, concentrations usually are <414 µeq/L, although some range up to 580 µeq/L, which suggests that elements of the distributed drainage system may become anoxic. Type C waters were the most dilute, yet they were very turbid. Their chemical composition is characterized by low SO42, : HCO3, ratios and high pH. Type C waters were usually artefacts of the borehole chemical weathering environment. True Type C waters are believed to flow through sulphide-poor basal debris, particularly in the channel marginal zone. The composition of bulk runoff was most similar to diluted Type B waters at high discharge, and was similar to a mixture of Type B and C waters at lower discharge. These observations suggest that some supraglacial meltwaters input to the bed are stored temporarily in the channel marginal zone during rising discharge and are released during declining flow. Little of the subglacial chemical weathering we infer is associated with the sequestration of atmospheric CO2. The progression of reactions is from carbonate and silicate hydrolysis, through sulphide oxidation by first oxygen and then FeIII, which drives further carbonate and silicate weathering. A crude estimate of the ratio of carbonate to silicate weathering following hydrolysis is 4 : 1. We speculate that microbial oxidation of organic carbon also may occur. Both sulphide oxidation and microbial oxidation of organic carbon are likely to drive the bed towards suboxic conditions. Hence, we believe that subglacial chemical weathering does not sequester significant quantities of atmospheric CO2 and that one of the key controls on the rate and magnitude of solute acquisition is microbial activity, which catalyses the reduction of FeIII and the oxidation of FeS2. Copyright © 2002 John Wiley & Sons, Ltd. [source] Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximabINFLAMMATORY BOWEL DISEASES, Issue 5 2008Antonio Di Sabatino MD Abstract Background: Under experimental chronic inflammation, tumor necrosis factor (TNF)-, plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-, is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients. Methods: Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells. Results: A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P < 0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P < 0.005). Splenic function was not ameliorated in nonresponder patients. Conclusions: Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation. (Inflamm Bowel Dis 2008) [source] Development of axonal pathways in the human fetal fronto-limbic brain: histochemical characterization and diffusion tensor imagingJOURNAL OF ANATOMY, Issue 4 2010Lana Vasung Abstract The development of cortical axonal pathways in the human brain begins during the transition between the embryonic and fetal period, happens in a series of sequential events, and leads to the establishment of major long trajectories by the neonatal period. We have correlated histochemical markers (acetylcholinesterase (AChE) histochemistry, antibody against synaptic protein SNAP-25 (SNAP-25-immunoreactivity) and neurofilament 200) with the diffusion tensor imaging (DTI) database in order to make a reconstruction of the origin, growth pattern and termination of the pathways in the period between 8 and 34 postconceptual weeks (PCW). Histological sections revealed that the initial outgrowth and formation of joined trajectories of subcortico-frontal pathways (external capsule, cerebral stalk,internal capsule) and limbic bundles (fornix, stria terminalis, amygdaloid radiation) occur by 10 PCW. As early as 11 PCW, major afferent fibers invade the corticostriatal junction. At 13,14 PCW, axonal pathways from the thalamus and basal forebrain approach the deep moiety of the cortical plate, causing the first lamination. The period between 15 and 18 PCW is dominated by elaboration of the periventricular crossroads, sagittal strata and spread of fibers in the subplate and marginal zone. Tracing of fibers in the subplate with DTI is unsuccessful due to the isotropy of this zone. Penetration of the cortical plate occurs after 24,26 PCW. In conclusion, frontal axonal pathways form the periventricular crossroads, sagittal strata and ,waiting' compartments during the path-finding and penetration of the cortical plate. Histochemistry is advantageous in the demonstration of a growth pattern, whereas DTI is unique for demonstrating axonal trajectories. The complexity of fibers is the biological substrate of selective vulnerability of the fetal white matter. [source] P,T conditions of decompression of the Limpopo high-grade terrane: record from shear zonesJOURNAL OF METAMORPHIC GEOLOGY, Issue 3 2001C. A. Smit Abstract The Southern Marginal Zone of the late Archean Limpopo Belt of southern Africa is an example of a high-grade gneiss terrane in which both upper and lower crustal deformational processes can be studied. This marginal zone consists of large thrust sheets of complexly folded low-strain gneisses, bound by an imbricate system of kilometre-wide deep crustal shear zones characterized by the presence of high-strain gneisses (,primary straight gneisses'). These shear zones developed during the decompression stage of this high-grade terrane. Low- and high-strain gneisses both contain similar reaction textures that formed under different kinematic conditions during decompression. Evidence for the early M1/D1 metamorphic phase (> 2690 Ma) is rarely preserved in low-strain gneisses as a uniform orientation of relict Al-rich orthopyroxene in the matrix and quartz and plagioclase inclusions in the cores of early (M1) Mg-rich garnet porphyroblasts. This rare fabric formed at >,820 °C and >,7.5 kbar. The retrograde M2/D2 metamorphic fabric (2630,2670 Ma) is well developed in high-strain gneisses from deep crustal shear zones and is microscopically recognized by the presence of reaction textures that formed synkinematically during shear deformation: M2 sigmoid-shaped reaction textures with oriented cordierite,orthopyroxene symplectites formed after the early M1 Mg-rich garnet porphyroblasts, and syn-decompression M2 pencil-shaped garnet with oriented inclusions of sillimanite and quartz formed after cordierite under conditions of near-isobaric cooling at 750,630 °C and 6,5 kbar. The symplectites and pencil-shaped garnet are oriented parallel to the shear fabric and in the stretching direction. Low-strain gneisses from thrust sheets show similar M2 decompression cooling and near-isobaric cooling reaction textures that formed within the same P,T range, but under low-strain conditions, as shown by their pseudo-idioblastic shapes that reflect the contours of completely replaced M1 garnet and randomly oriented cordierite,orthopyroxene symplectites. The presence of similar reaction textures reflecting low-strain conditions in gneisses from thrust sheets and high-strain conditions in primary straight gneisses suggests that most of the strain during decompression was partitioned into the bounding shear zones. A younger M3/D3 mylonitic fabric (< 2637 Ma) in unhydrated mylonites is characterized by brittle deformation of garnet porphyroclasts and ductile deformation of the quartz,plagioclase,biotite matrix developed at <,600 °C, as the result of post-decompression shearing under epidote,amphibolite facies conditions. [source] Splenic marginal zone antigen-presenting cells are critical for the primary allo-immune response to therapeutic factor VIII in hemophilia AJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2009A. NAVARRETE Summary.,Background: Alloimmune responses to intravenously administered protein therapeutics are the most common cause of failure of replacement therapy in patients with defective levels of endogenous proteins. Such a situation is encountered in some patients with hemophilia A, who develop inhibitory anti-factor (F)VIII alloantibodies after administration of FVIII to treat hemorrhages. Objectives: The nature of the secondary lymphoid organs involved in the initiation of immune responses to human therapeutic has not been studied. We therefore investigated this in the case of FVIII, a self-derived exogenous protein therapeutic. Methods: The distribution of intravenously administered FVIII was followed after FVIII-deficient mice were injected with radiolabeled FVIII and using immunohistochemistry. The role of the spleen and antigen-presenting cells (APC) in the onset of the anti-FVIII immune response was analyzed upon splenectomy or treatment of the mice with APC-depleting compounds. Results: FVIII preferentially accumulated in the spleen at the level of metallophilic macrophages in the marginal zone (MZ). Surgical removal of the spleen or selective in vivo depletion of macrophages and CD11c-positive CD8,-negative dendritic cells resulted in a drastic reduction in anti-FVIII immune responses. Conclusions: Using FVIII-deficient mice as a model for patients with hemophilia A, and human pro-coagulant FVIII as a model for immunogenic self-derived protein therapeutics, our results highlight the importance of the spleen and MZ APCs in the initiation of immune responses to protein therapeutics. Identification of the receptors implicated in retention of protein therapeutics in the MZ may pave the way towards novel strategies aimed at reducing their immunogenicity. [source] Isolation and characterization of a novel Xenopus gene (xVAP019) encoding a DUF1208 domain containing proteinMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 12 2007Xu Zhi Ruan Abstract We have identified a novel Xenopus gene (xVAP019) encoding a DUF1208 domain containing protein. Using whole-mount in situ hybridization and RT-PCR, we found abundant xVAP019 maternal transcripts in the animal hemisphere during the cleavage stages and blastula stages. During gastrulation xVAP019 is differentially expressed with higher levels in the animal helf and the highest in marginal zone, then further expressed widely at neuronal stages with strongest signals in the prospective CNS regions and the epidermal ectoderm. Subsequently xVAP019 was expressed predominantly in the head, the eyes, the otic vesicle, branchial arches, spinal cord, notochord, somites, and tailbud. It is absent or very weak in the endoderm. Injecting a morpholino oligo complementary to xVAP019 mRNA or injecting a caped xVAP019 mRNA caused most of embryos to die during gastrulation and neurulation. Overexpression of xVAP019 mRNA also led to eye defect, shorten interocular distance, small body size and abnormal pigment formation in parts of the survival embryos. Similar effects were induced by injecting the xVAP019 human homologous gene FAM92A1. Our results suggest that xVAP019 is essential for the normal ectoderm and axis mesoderm differentiation and embryos survival. This investigation is for the first time in vivo study examining the role of this novel gene and reveals an important role of xVAP019 in embryonic development. Mol. Reprod. Dev. 74: 1505,1513, 2007. © 2007 Wiley-Liss, Inc. [source] Inflammation and structural changes of splenic lymphoid tissue in visceral leishmaniasis: A study on naturally infected dogsPARASITE IMMUNOLOGY, Issue 10 2008C. C. SANTANA SUMMARY The aim of this study was to identify splenic immuno-inflammatory patterns associated with natural infection by Leishmania chagasi. Spleen samples were obtained from 72 stray dogs from an endemic area of visceral leishmaniasis. The animals were grouped into four categories as follows: (i) potentially resistant to visceral leishmaniasis, with a positive leishmanin skin test result, and negative splenic culture for Leishmania parasites (ii) potentially susceptible to visceral leishmaniasis, with a negative leishmanin skin test and positive splenic culture for Leishmania (iii) infected with undefined susceptibility status, with a positive leishmanin skin test and positive splenic culture for Leishmania, and (iv) noninfected, with a negative leishmanin skin test, negative splenic culture for Leishmania, and negative serology for anti- Leishmania antibodies. Histopathological analyses showed that there was a higher frequency of perisplenitis (18/25, P < 0·0001), granuloma (7/25, P = 0·0102), structural disorganization (14/25, P < 0·0001), and atrophy of the lymphoid follicles (20/25, P = 0·0036) and of the marginal zone (15/25, P = 0·0025) in the potentially susceptible group than in the other groups. The data presented here show changes in the white pulp of the spleen that are associated with naturally acquired visceral leishmaniasis. [source] Rescue of the reeler phenotype in the dentate gyrus by wild-type coculture is mediated by lipoprotein receptors for reelin and disabled 1THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2006Shanting Zhao Abstract Reelin is a positional signal for the lamination of the dentate gyrus. In the reeler mutant lacking Reelin, granule cells are scattered all over the dentate gyrus. We have recently shown that the reeler phenotype of the dentate gyrus can be rescued in vitro by coculturing reeler hippocampal slices with slices from wild-type hippocampus. Here we studied whether Reelin from other brain regions can similarly induce this rescue effect and whether it is mediated via the Reelin receptors apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR). We found that coculturing reeler hippocampal slices with slices from wild-type olfactory bulb, cerebellum, and neocortex rescued the reeler phenotype as seen before with hippocampal slices, provided that the Reelin-synthesizing cells of these regions were placed near the marginal zone of the reeler hippocampal slice. However, coculturing wild-type hippocampal slices with hippocampal slices from mutants deficient in ApoER2 and VLDLR did not rescue the reeler-like phenotype in these cultures. Similarly, no rescue of the reeler-like phenotype was observed in slices from mutants lacking Disabled 1 (Dab1), an adapter protein downstream of Reelin receptors. Conversely, reeler hippocampal slices were rescued by coculturing them with slices from Dab1,/, mutants or ApoER2,/,/VLDLR,/, mice. These findings show that Reelin from other brain regions can substitute for the loss of hippocampal Reelin and that rescue of the reeler phenotype observed in our coculture studies is mediated via lipoprotein receptors for Reelin and Dab1. J. Comp. Neurol. 495:1,9, 2006. © 2006 Wiley-Liss, Inc. [source] Axonal secretion of reelin by cajal-retzius cells: Evidence from comparison of normal and RelnOrl mutant miceTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2001Paul Derer Abstract A novel secretory pathway has been identified in the study of mice homozygous for the RelnOrl mutation, a line characterised by the defective secretion of the large extracellular matrix glycoprotein Reelin. By using both light and electron microscopy, immunohistochemical studies for Reelin in these mutants identified morphological changes in their Cajal-Retzius cells (CR cells). The CR cells of the mutant displayed the characteristic features of bipolar, tangentially elongated neurons with a dendritic proximal pole and an axonal cone at the opposite end of the soma. At either pole, cisterns of prominent rough endoplasmic reticulum (RER) were found to be rich in Reelin. However, the Reelin-positive RER cisterns of the axonal cones were hugely dilated in homozygous RelnOrl mice as compared with their wild type counterparts. CR cell axons displayed beads throughout their length, each contained a smooth spheroidal cistern filled with Reelin-immunoreactive fibrillar material, and were increased in number and size in RelnOrl mice. RER phenotype was rescued in the RelnAlb2 mice, a mutation in which no Reelin protein is produced. We propose that the RER dilations viewed in the RelnOrl mutation are due to the accumulation of the defective Reelin protein, and the large axonal beads in RelnOrl mice reflect the accumulation of truncated Reelin as the result of defects in its secretion. These observations point to an original, hitherto unrecognised, mechanism of secretion by bulk transport in smooth cisterns from the axonal cone into the axon, followed by secretion in the cortical marginal zone from the axonal cisterns that we have named axonal reelin reservoirs. J. Comp. Neurol. 440:136,143, 2001. © 2001 Wiley-Liss, Inc. [source] Prolonged effects of short-term anti-CD20 B cell depletion therapy in murine systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 8 2010Kai W. Bekar Objective Although B cells are implicated in the pathogenesis of systemic lupus erythematosus, the role of B cell depletion (BCD) as a treatment is controversial, given the variable benefit in human disease. This study was undertaken to test the effects of BCD therapy in a murine lupus model to better understand the mechanisms, heterogeneity, and effects on disease outcomes. Methods (NZB × NZW)F1 female mice with varying degrees of disease severity were treated with an anti-mouse CD20 (anti-mCD20) antibody (IgG2a), BR3-Fc fusion protein (for BAFF blockade), or control anti-human CD20 monoclonal antibody (,10 mg/kg each). Tissue samples were harvested and analyzed by flow cytometry. The development and extent of nephritis were assessed by monitoring proteinuria (using a urine dipstick) and by immunohistochemical analysis of the kidneys. Serum immunoglobulin levels were measured by enzyme-linked immunosorbent assay. Results After a single injection of anti-mCD20, BCD was more efficient in the peripheral blood, lymph nodes, and spleen compared with the bone marrow and peritoneum of normal mice as well as younger mice with lupus. Since depletion of the marginal zone and peritoneal B cells was incomplete and variable, particularly in older mice with established nephritis, a strategy of sequential weekly dosing was subsequently used, which improved the extent of depletion. BAFF blockade further enhanced depletion in the spleen and lymph nodes. Early BCD therapy delayed disease onset, whereas BCD therapy in mice with advanced disease reduced the progression of nephritis. These effects were long-lasting, even after B cell reconstitution occurred, and were associated with a reduction in T cell activation but no significant change in autoantibody production. Conclusion The lasting benefit of a short course of BCD therapy in lupus-prone mice with an intact immune system and established disease highlights the validity of this treatment approach. [source] Crystallization and preliminary X-ray diffraction studies of the carbohydrate-recognition domain of SIGN-R1, a receptor for microbial polysaccharides and sialylated antibody on splenic marginal zone macrophagesACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 12 2009Noella Silva-Martin SIGN-R1, or CD209b, is a mouse C-type lectin receptor that is expressed at high levels on macrophages in lymphoid tissues, especially within the marginal zone of the spleen. SIGN-R1 can bind and mediate the uptake of various microbial polysaccharides, including dextrans, lipopolysaccharides and pneumococcal capsular polysaccharides. It has been shown that SIGN-R1 mediates the clearance of encapsulated pneumococcus, complement fixation via binding C1q independent of antibody and innate resistance to pneumococcal infection. Recently, SIGN-R1 has also been demonstrated to bind sialylated antibody and mediate its activity to suppress autoimmunity. The carbohydrate-recognition domain (CRD) of SIGN-R1 has been cloned and overexpressed in a soluble secretory form in mammalian Chinese hamster ovary (CHO) cells. The CRD protein of SIGN-R1 was purified from CHO cell-culture supernatant and concentrated for crystallization using the hanging-drop vapour-diffusion method at 291,K. Crystals grew from a mixture of 2,M ammonium sulfate in 0.1,M bis-tris pH 5.5. Single crystals, which belonged to the monoclinic space group C2 with unit-cell parameters a = 146.72, b = 92.77, c = 77.06,Å, , = 121.66°, allowed the collection of a full X-ray data set to a maximum resolution of 1.87,Å. [source] Quantification of dead-ice melting in ice-cored moraines at the high-Arctic glacier Holmströmbreen, SvalbardBOREAS, Issue 2 2008ANDERS SCHOMACKER An extensive dead-ice area has developed at the stagnant snout of the Holmströmbreen glacier, Svalbard, following its last advance during the Little Ice Age (LIA). The most common landform is ice-cored slopes hosting sediment gravity flows. Dead-ice melting is described and quantified through field studies and analyses of high-resolution, multi-temporal aerial photographs and QuickBird 2 satellite imagery. Field measurements of backwasting of ice-cored slopes indicate melting rates of 9.2 cm/day. Downwasting rates reveal a dead-ice surface lowering of 0.9 m/yr from 1984 to 2004. The volume of melted dead-ice in the marginal zone since the LIA is estimated at 2.72 km3. Most prominently, dead-ice melting causes the growth of an ice-walled lake with an area increasing near-exponentially over the last 40 years. Despite the high-Arctic setting, dead-ice melting progresses with similar rates as in humid sub-polar climates, stressing that melt rates are governed by processes and topography rather than climate. We suggest that the permafrost and lack of glacier karst prevent meltwater percolation, thus maintaining a liquefied debris-cover where new dead-ice is continuously exposed to melting. As long as backwasting and mass movement processes prevent build-up of an insulating debris-cover, the de-icing continues despite the continuous permafrost. [source] The Keiva ice marginal zone on the Kola Peninsula, northwest Russia: a key component for reconstructing the palaeoglaciology of the northeastern Fennoscandian Ice SheetBOREAS, Issue 4 2007Clas H, ttestrand One of the key elements in reconstructing the palaeoglaciology of the northeastern sector of the Fennoscandian Ice Sheet is the Keiva ice marginal zone (KIZ) along the southern and eastern coast of Kola Peninsula, including the Keiva I and II moraines. From detailed geomorphological mapping of the KIZ, primarily using aerial photographs and satellite images, combined with fieldwork, we observed the following. (1) The moraines display ice contact features on both the Kola side and the White Sea side along its entire length. (2) The Keiva II moraine is sloping along its length from c. 100 m a.s.l. in the west (Varzuga River) to c. 250 m a.s.l. in the east (Ponoy River). (3) The KIZ was partly overrun and fragmented by erosive White Sea-based ice after formation. From these observations we conclude that the KIZ is not a synchronous feature formed along the lateral side of a White Sea-based ice lobe. If it was, the moraines should have a reversed slope. Rather, we interpret it to be time transgressive, formed at a northeastward-migrating junction between a warm-based Fennoscandian Ice Sheet expanding from the west and southwest into the White Sea depression, and a sluggish cold-based ice mass centred over eastern Kola Peninsula. In contrast to earlier reconstructions, we find it unlikely that an ice expansion of this magnitude was a mere re-advance during the deglaciation. Instead, we propose that the KIZ was formed during a major expansion of a Fennoscandian Ice Sheet at a time pre-dating the Last Glacial Maximum. [source] Primary cutaneous B-cell lymphoma (marginal zone) with prominent T-cell component and aberrant dual (T and B) genotype; diagnostic usefulness of laser-capture microdissectionBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006F. Gallardo Summary The presence of a dominant B- or T-cell clone is an important diagnostic criterion for distinguishing cutaneous lymphomas from lymphoid reactive infiltrates. Rarely, a combined B- and T-cell rearrangement can be detected from a single sample. In such instances, genotypic analysis does not permit differentiation of the coexistence of a T- and B-cell lymphoma from a single clone harbouring a monoclonal rearrangement for both immunoglobulin heavy chain and T-cell receptor genes. We herein report a case of a skin tumour consistent with a dense cutaneous lymphoid infiltrate showing a double prominent B- and T-cell component. A dual B- and T-cell clonality was detected by polymerase chain reaction from whole-tissue DNA sample. Genotypic analysis with DNA, obtained after laser-assisted microdissection from the B-cell population, again showed both T- and B-cell monoclonal rearrangements. Conversely, the microdissected T-cell population did not reveal a clonal pattern. The diagnosis of cutaneous B-cell lymphoma with a dual B- and T-cell genotype was established. This description illustrates the diagnostic usefulness of laser-capture microdissection in cutaneous lymphomas presenting dual genotype. [source] Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexaCANCER, Issue 4 2003A multiinstitutional, retrospective review of 50 patients Abstract BACKGROUND Due to the small number of patients and differences in the pathologic classification in most radiotherapy series, information regarding the adequacy of tumor control in patients with ocular-adnexal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is limited. METHODS A multiinstitutional, retrospective study was performed on 50 patients with Stage IE ocular-adnexal MALT lymphoma who were treated with radiotherapy between 1989 and 1999. The impact of patient characteristics and other variables on tumor control was analyzed. RESULTS Responses to radiotherapy include a complete response (CR) in 26 patients, a partial response (PR) in 20 patients, and no change in 4 patients. Forty-nine of 50 patients obtained tumor control in the ocular adnexa at 24 months. Overall, 6 patients exhibited disease recurrence at 4,97 months. Three patients developed recurrence in the ocular adnexa. Two patients had isolated extranodal failure involving the oral floor and the submandibular gland, and one patient experienced failure in the neck lymph node. The initial tumor response had a marginal impact on the development of recurrence. None of the 26 patients who achieved a CR experienced ocular-adnexal recurrence. All three patients who experienced local treatment failure belonged to the initial PR group. In total, five of six patients who developed recurrent disease had obtained a PR after initial radiotherapy. Age, gender, tumor location, and dose of radiotherapy did not influence the development of recurrence. There was only one death due to lymphoma. The 5-year overall survival rate was 91% with a median follow-up of 46 months. CONCLUSIONS Radiotherapy offers excellent local control with a prolonged clinical course for patients with MALT lymphoma in the ocular adnexa. The initial response to radiotherapy marginally influenced the probability of recurrence. Cancer 2003;98:865,71. © 2003 American Cancer Society. DOI 10.1002/cncr.11539 [source] Current and possible future treatment of ocular adnexal lymphomasACTA OPHTHALMOLOGICA, Issue 2008A PETTITT Purpose To review the current and possible future therapies of ocular adnexal lymphomas. Methods Ocular adnexal lymphomas represent approx. 8% of all extranodal lymphomas. The majority of these can be classified as extranodal marginal zone (MALT) lymphomas, and are usually staged as Stage IE disease. Results Recommended therapy in Stage IE tumours is low-dose radiotherapy, while disseminated disease (>Stage IIE) is treated with chemotherapy. Although often responding to initial therapy, the MALT lymphomas tend to recur in distant extranodal sites. Few biomarkers are available to aid prediction of either recurrence or systemic dissemination, which occurs in up to 25% of patients. The ocular morbidity associated with current therapies is not insignificant, and, therefore, more effective treatment is being sought. Conclusion The newer treatment options, including rituximab and doxycyclin, will be discussed [source] BAFF: a local and systemic target in autoimmune diseasesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2009I. Moisini Summary BAFF (B lymphocyte activating factor of the tumour necrosis factor family) is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. Increased serum levels of BAFF are found in a number of different autoimmune diseases, and BAFF is found in inflammatory sites in which there is lymphoid neogenesis. BAFF antagonism has been used in several autoimmune disease models, resulting in B cell depletion, decreased activation of T cells and dendritic cells (DC) and a reduction in the overall inflammatory burden. BAFF, through its interaction with BAFF-R, is required for survival of late transitional, marginal zone and mature naive B cells, all of which are depleted by BAFF blockade. Through their interactions with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B cell maturation protein), BAFF and its homologue APRIL (a proliferation-inducing ligand), support the survival of at least some subsets of plasma cells; blockade of both cytokines results in a decrease in serum levels of immunoglobulin (Ig)G. In contrast, neither BAFF nor APRIL is required for the survival or reactivation of memory B cells or B1 cells. BAFF also helps DC maturation and interleukin (IL)-6 release and is required for proper formation of a follicular dendritic cell (FDC) network within germinal centres, although not for B cell affinity maturation. The clinical efficacy of BAFF blockade in animal models of autoimmunity may be caused both by the decline in the number of inflammatory cells and by the inhibition of DC maturation within target organs. Blockade of BAFF and its homologue APRIL are being explored for human use; several Phase I and II clinical trials of BAFF inhibitors for autoimmunity have been completed and Phase III trials are in progress. [source] | |||||||||||||||||||