Sample records for basement membrane pathology

  1. Basement membrane proteoglycans and development

    DEFF Research Database (Denmark)

    Couchman, J R; Abrahamson, D R; McCarthy, K J


    Basement membranes contain distinct collagen, glycoprotein and proteoglycan species, and these exhibit considerable heterogeneity in isoform or type when different tissue types are compared. Additionally, many components are differentially expressed in organogenesis. We have considered the distri......Basement membranes contain distinct collagen, glycoprotein and proteoglycan species, and these exhibit considerable heterogeneity in isoform or type when different tissue types are compared. Additionally, many components are differentially expressed in organogenesis. We have considered...... the distributions in glomerulogenesis of two distinct basement membrane proteoglycans, a small heparan sulfate proteoglycan and a chondroitin sulfate proteoglycan (BM-CSPG). While the former was present in all kidney basement membranes through development, the latter was apparently regulated in distribution. BM......-CSPG was only strongly expressed in the vasculature invading late comma stage glomeruli, and later in presumptive and mature Bowman's capsule. Over the first six to eight weeks, the capillary basement membranes contained BM-CSPG, but in gradually decreasing amounts until it became completely undetectable...

  2. Laminins in basement membrane assembly. (United States)

    Hohenester, Erhard; Yurchenco, Peter D


    The heterotrimeric laminins are a defining component of all basement membranes and self-assemble into a cell-associated network. The three short arms of the cross-shaped laminin molecule form the network nodes, with a strict requirement for one α, one β and one γ arm. The globular domain at the end of the long arm binds to cellular receptors, including integrins, α-dystroglycan, heparan sulfates and sulfated glycolipids. Collateral anchorage of the laminin network is provided by the proteoglycans perlecan and agrin. A second network is then formed by type IV collagen, which interacts with the laminin network through the heparan sulfate chains of perlecan and agrin and additional linkage by nidogen. This maturation of basement membranes becomes essential at later stages of embryo development.

  3. The nature and biology of basement membranes. (United States)

    Pozzi, Ambra; Yurchenco, Peter D; Iozzo, Renato V


    Basement membranes are delicate, nanoscale and pliable sheets of extracellular matrices that often act as linings or partitions in organisms. Previously considered as passive scaffolds segregating polarized cells, such as epithelial or endothelial cells, from the underlying mesenchyme, basement membranes have now reached the center stage of biology. They play a multitude of roles from blood filtration to muscle homeostasis, from storing growth factors and cytokines to controlling angiogenesis and tumor growth, from maintaining skin integrity and neuromuscular structure to affecting adipogenesis and fibrosis. Here, we will address developmental, structural and biochemical aspects of basement membranes and discuss some of the pathogenetic mechanisms causing diseases linked to abnormal basement membranes.

  4. How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases (United States)

    Rodriguez-Teja, Mercedes; Breit, Claudia; Clarke, Mitchell; Talar, Kamil; Wang, Kai; Mohammad, Mohammad A.; Pickwell, Sage; Etchandy, Guillermina; Stasiuk, Graeme J.; Sturge, Justin


    Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under

  5. ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity. (United States)

    Daley, William P; Gervais, Elise M; Centanni, Samuel W; Gulfo, Kathryn M; Nelson, Deirdre A; Larsen, Melinda


    The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin β1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.

  6. Basement membrane proteoglycans are of epithelial origin in rodent skin

    DEFF Research Database (Denmark)

    Yamane, Y; Yaoita, H; Couchman, J R


    proteoglycan and rat and mouse perlecan. While the isolated rat epidermis was shown to completely lack rat basement membrane chondroitin sulfate proteoglycan and rat basement membrane heparan sulfate proteoglycans, including perlecan, immunofluorescence staining of tissue sections from the grafted sites......-epidermal junction and hair follicle epithelium are of epidermal (epithelial) origin in vivo. Stratified rat keratinocytes cultured on a collagen matrix at the air-liquid interface showed the synthesis of perlecan, laminin 1, and type IV collagen in basement membranes, but not clearly detectable basement membrane...

  7. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. (United States)

    Mao, Mao; Alavi, Marcel V; Labelle-Dumais, Cassandre; Gould, Douglas B


    Basement membranes are highly specialized extracellular matrices. Once considered inert scaffolds, basement membranes are now viewed as dynamic and versatile environments that modulate cellular behaviors to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to neighboring cells, basement membranes serve as reservoirs of growth factors that direct and fine-tune cellular functions. Type IV collagens are a major component of all basement membranes. They evolved along with the earliest multicellular organisms and have been integrated into diverse fundamental biological processes as time and evolution shaped the animal kingdom. The roles of basement membranes in humans are as complex and diverse as their distributions and molecular composition. As a result, basement membrane defects result in multisystem disorders with ambiguous and overlapping boundaries that likely reflect the simultaneous interplay and integration of multiple cellular pathways and processes. Consequently, there will be no single treatment for basement membrane disorders, and therapies are likely to be as varied as the phenotypes. Understanding tissue-specific pathology and the underlying molecular mechanism is the present challenge; personalized medicine will rely upon understanding how a given mutation impacts diverse cellular functions.

  8. A Review on the Potential Role of Basement Membrane Laminin in the Pathogenesis of Psoriasis. (United States)

    McFadden, J P; Kimber, I


    We have previously reviewed alterations to basement membrane laminin in psoriasis and how disruption of this layer could lead to at least some of the pathological changes observed. We here postulate that basement membrane laminin is the key antigen in driving psoriasis, inducing a T cell-mediated autoimmune response. For laminin to be considered as the key autoantigen in psoriasis, it would be reasonable to expect the following to be demonstrable: (1) that autoantigens are present in psoriatic inflammation; (2) that basement membrane laminin is perturbed in involved and uninvolved skin, and that some of the pathological changes associated with psoriasis could be predicted as a sequel to this; (3) that disruption of the basement membrane is among the earliest events in the evolution of psoriatic lesions; (4) that as streptococcal pharyngitis is the most clearly defined event to trigger or exacerbate psoriasis, then a T cell-mediated autoimmune response to laminin should be anticipated as a potential sequelae to streptococcal pharyngitis; (5) that T cells in psoriasis can be shown to react to peptides with homology to laminin; (6) that HLACw6, as the most closely related gene associated with psoriasis and which is involved in antigen expression, should be preferentially expressed within lesional psoriasis towards the basement membrane, together with other proximal associated immune activity; and (7) that there is some association between antilaminin pemphigoid, a humorally mediated autoimmune disease to skin basement membrane laminin, and psoriasis. We here review the data relevant to each of these requirements.

  9. The major basement membrane components localize to the chondrocyte pericellular matrix--a cartilage basement membrane equivalent?

    DEFF Research Database (Denmark)

    Kvist, Alexander J.; Nyström, Alexander; Hultenby, Kjell;


    In this study, we demonstrate that articular cartilage chondrocytes are surrounded by the defining basement membrane proteins laminin, collagen type IV, nidogen and perlecan, and suggest that these form the functional equivalent of a basement membrane. We found by real-time PCR that mouse chondro...... to the progression of degenerative joint disorders....

  10. Basement membrane-specific chondroitin sulfate proteoglycan is abnormally associated with the glomerular capillary basement membrane of diabetic rats

    DEFF Research Database (Denmark)

    McCarthy, K J; Abrahamson, D R; Bynum, K R;


    We have previously reported the production of monoclonal antibodies (MAb) recognizing the core protein of a basement membrane-specific chondroitin sulfate proteoglycan (BM-CSPG). Using immunohistochemical techniques, we have shown that BM-CSPG is present in almost every basement membrane, one...


    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Autoimmune mucocutaneous blistering diseases (ABDs represent a group of conditions that manifest with blisters on the skin and/or mucous membranes. Bullous pemphigoid (BP is the most common autoimmune mucocutaneous blistering disease. In BP, the location of the blisters is subepidermal and the oral involvement is rare. Variants of BP have been described, including pemphigoid vegetans; however, this disease is not completely characterized. The majority of ABDs have blisters and/or vesicles, that are often pruritic, and manifest autoantibodies to diverse proteins. These proteins include 1 hemidesmosomal plaque proteins(ie, BP230, plectins, 2 transmembrane proteins such as BP180 and α6β4-integrin, which are connected via laminin 332 to type VII collagen and 3 currently uncharacterized 105 kDa and 200 kDa molecules. Other ABDs include drug-induced linear IgA disease, bullous systemic lupus erythematosus (BSLE, dermatitis herpetiformis (DH, cicatricial pemphigoid (CP; also termed mucous membrane pemphigoid, lichen planus pemphigoides (LPP, pemphigoid gestationis (PG, herpes gestationis(HG, chronic bullous dermatosis of childhood (CBDC and the localized forms of CP, such as Brunsting-Perry pemphigoid. The diagnosis of ABDs requires clinical data; skin biopsies (in 10% buffered formalin for hematoxylin and eosin (H&E examination and skin biopsies(in Michel’s transport medium for direct immunofluorescence (DIF. In many ABDs, the histopathologic findings demonstrate a subepidermal vesicle or bulla with a luminal inflammatory infiltrate of neutrophils, eosinophils and/or lymphocytes. In many ABDs, an extensive perivascular and interstitial inflammatory infiltrate is also noted subjacent to the blister in the upper dermis. Normal skin adjacent to an ABD plaque is often excellent for DIF results. Many ABD biopsies reveal autoantibody deposition at the lesional basement membrane zone (BMZ; IgG, IgM, IgA, other immunoglobulins, complement components and

  12. Coarctation induces alterations in basement membranes in the cardiovascular system

    DEFF Research Database (Denmark)

    Lipke, D W; McCarthy, K J; Elton, T S;


    A coarctation hypertensive rat model was used to examine the effects of elevated blood pressure on basement membrane component synthesis by cardiac myocytes and aorta using immunohistochemistry and Northern blot analysis. Carotid arterial pressure increased immediately on coarctation, and left...

  13. Expression of VLA-integrins and their related basement membrane ligands in gingiva from patients of various periodontitis categories

    DEFF Research Database (Denmark)

    Gürses, N.; Thorup, Alis Karabulut; Reibel, J.;


    integrins, basement membrane, gingiva, periodontitis, periodontal disease activity immunofluorescence......integrins, basement membrane, gingiva, periodontitis, periodontal disease activity immunofluorescence...

  14. The clinical utility of reticular basement membrane thickness measurements in asthmatic children

    NARCIS (Netherlands)

    van Mastrigt, Esther; Vanlaeken, Leonie; Heida, Fardou; Caudri, Daan; de Jongste, Johan C.; Timens, Wim; Rottier, Bart L.; de Krijger, Ronald R.; Pijnenburg, Marielle W.


    Objective: Reticular basement membrane (RBM) thickness is one of the pathological features of asthma and can be measured in endobronchial biopsies. We assessed the feasibility of endobronchial biopsies in a routine clinical setting and investigated the clinical value of RBM thickness measurements fo

  15. Expression of basement membrane antigens in spindle cell melanoma. (United States)

    Prieto, V G; Woodruff, J M


    Spindle cell melanoma (SCM) is an uncommon form of melanoma that may be confused histologically with other tumors, including malignant peripheral nerve sheath tumors (MPNST). Tumors with neural differentiation and melanocytic nevi may both show basement membrane immunohistochemically and at the ultrastructural level. However, most ultrastructural studies of melanoma have failed to demonstrate well formed basement membrane around tumor cells. The presence of basement membrane has been used by some authors as evidence favoring MPNST, as opposed to SCM. To evaluate this distinction immunohistochemically, 22 primary and metastatic cutaneous melanomas having a spindle cell component (SCM) were studied using monoclonal antibodies against laminin and Type IV collagen. S100 protein and HMB45 antigen expression were also studied. All but one of the SCM were reactive for S100 protein in at least 25% of the cells. Thirteen of 20 tumors (65%) were focally reactive with HMB45. Laminin was expressed in 42% of the tumors (only membranous pattern in 3; cytoplasmic and membranous in 5). Seventeen tumors (77%) expressed type IV collagen (only membranous pattern in 7; cytoplasmic and membranous pattern in 10). Laminin and type IV collagen, known components of basement membrane, are often found in SCM. Therefore, their detection cannot be used to distinguish SCM from MPNST.

  16. Abnormal glomerular basement membrane in idiopathic multicentric osteolysis

    NARCIS (Netherlands)

    Bakker, SJL; Vos, GD; Verschure, PDMM; Mulder, AH; Tiebosch, TMG


    The primary cause of nephropathy in idiopathic multicentric osteolysis is as yet unknown. We report a young girl with idiopathic multicentric osteolysis and nephropathy. An abnormal glomerular basement membrane was the only abnormality found in a renal biopsy taken 2 years before the development of

  17. Ultrastructure of basement membranes in developing shark tooth. (United States)

    Sawada, T; Inoue, S


    Based on studies of the tooth of largely mammalian species, the dental basement membranes are shown to be specialized for various roles significant in the development and maintenance of the tooth. Comparative studies with the nonmammalian tooth will facilitate further clarification of the mechanisms of mammalian tooth formation. In this study, basement membranes of the shark tooth in successive developmental stages was ultrastructurally examined for elucidation of their roles in odontogenesis. Teeth of a shark, Cephaloscyllium umbratile, were processed for thin section electron microscopy. Throughout the developmental stages the lamina densa of the basement membrane was made up of a fine network of "cords," irregular anastomosing strands known to be the major component of mammalian basement membranes. In the presecretory stage of the shark tooth, dental papilla cells were immobilized for their differentiation into odontoblasts by means of the binding of their processes to numerous narrow extensions of the lamina densa of the inner dental epithelium. In the secretory stage, a number of cords of the widened lamina densa were extended towards and bound to tubular vesicles of the forming enameloid. During the mineralization stage, fragments of the degrading enameloid matrix appeared to be moving through the lamina densa to the epithelial cells for processing. In the maturation stage, half of the lamina densa facing the enameloid was mineralized forming an advancing edge of mineralization of the enameloid. It provided strong binding and smooth transition of organic to mineral phase which may allow transportation of substances across the phases for enameloid maturation in a way similar to that reported in the mammalian tooth. These observations indicate that basement membranes of the developing shark tooth, as those in the mammalian tooth, play various roles, including anchoring, firm binding, and possible mediation of the transport of substances that are known to be

  18. Superficial Dermal Fibroblasts Enhance Basement Membrane and Epidermal Barrier Formation in Tissue-Engineered Skin: Implications for Treatment of Skin Basement Membrane Disorders



    Basement membrane is a highly specialized structure that binds the dermis and the epidermis of the skin, and is mainly composed of laminins, nidogen, collagen types IV and VII, and the proteoglycans, collagen type XVIII and perlecan, all of which play critical roles in the function and resilience of skin. Both dermal fibroblasts and epidermal keratinocytes contribute to the development of the basement membrane, and in turn the basement membrane and underlying dermis influence the development ...

  19. Regulation of the basement membrane by epithelia generated forces (United States)

    Tanner, Kandice


    Tumor metastasis involves a progressive loss of tissue architecture and dissolution of structural boundaries between the epithelium and connective tissue. The basement membrane (BM), a specialized network of extracellular matrix proteins forms a barrier that physically restricts pre-invasive lesions such that they remain as local insults. The BM is not a static structure, but one that is constantly regenerated and remodeled in the adult organism. Matrix organization also regulates cell function. Thus alterations in the balance of synthesis, remodeling and proteolytic degradation of the extracellular matrix proteins may contribute to a loss of structural integrity. However, the de novo assembly and maintenance of the complex structural properties of in vivo basement membranes remain elusive. Here, this paper highlights the current understanding on the structural properties and the establishment of the BM, and discusses the potential role of self-generated forces in adult tissue remodeling and the maintenance of the BM as a malignancy suppressor.

  20. Antiglomerular basement membrane antibody-crescentic glomerulonephritis complicating chronic bronchiectasis. (United States)

    Enríquez, R; Cabezuelo, J B; Sirvent, A E; Andrada, E; Amorós, F; Orti, C


    A 68-year-old woman with chronic bronchiectasis presented with haematuria and severe oligoanuric renal failure with no other serious systemic manifestation. Antiglomerular basement membrane (anti-GBM) antibodies and anti-myeloperoxidase antibodies were positive. Renal biopsy revealed anti-GBM crescentic glomerulonephritis. A conservative approach was followed and the patient is stable on chronic haemodialysis 6 months later. To the authors' knowledge, there has only been one previous report of anti-GBM disease complicating bronchiectasis.

  1. Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R


    Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... sulfate proteoglycans previously described....

  2. Effects of radiation on the permeability of human basement membranes (United States)

    Fan, B.-T.; Achour, S.; Simmonet, F.; Guerin, D.


    The influence of radiation on the permeability properties of human basement membrane was investigated by measuring the diffusion rate of several organic compounds (glycine, proline, glucose, urea and insulin) through human anterior lens capsules. The basement membranes borne an γ-irradiation treatment change significantly their permeability vis-a-vis studied organic substances. This modification in physico-chemical properties is probably due to the radiation, which alters or degrades the complex structure (or architecture) of basement membranes. Moreover the change in permeability is dependent upon the diffusing compounds. An increase in diffusion has been observed for glucose, glycine and urea. However for insulin and proline, a decrease in diffusion rate was observed. L'influence de radiation sur la perméabilité de la membrane basale a été étudiée par la mesure de la vitesse de diffusion de plusieurs composés organiques d'intérêt biologique (glycine, proline, glucose, urée et insuline) à travers la lame basale antérieure du cristallin de l'oil humain. Les membranes basales qui sont traitées avec l'irradiation γ changent significativement leur perméabilité vis-à-vis des substances organiques. Ce changement de propriétés physico-chimiques est probablement dû à l'altération ou la dégradation de la structure (ou de l'architecture) de la membrane basale entraînée par l'irradiation. De plus, la modification de la perméabilité de la membrane basale est dépendante des composés diffusants. Une augmentation de la vitesse de diffusion a été observée pour le glucose, le glycine et l'urée. Par contre, dans les cas de l'insuline et de la proline, on a observé une diminution de la vitesse de diffusion.

  3. Immunohistochemical localization of basement membrane components during hair follicle morphogenesis

    DEFF Research Database (Denmark)

    Westgate, G E; Shaw, D A; Harrap, G J


    Specific antisera were used to investigate the distributions of several basement membrane zone (BMZ) components, namely, bullous pemphigoid antigen (BPA), heparan sulfate proteoglycan (HSPG), laminin, and type IV collagen, during the development of hair follicles in late embryo rats. BPA was not ......Specific antisera were used to investigate the distributions of several basement membrane zone (BMZ) components, namely, bullous pemphigoid antigen (BPA), heparan sulfate proteoglycan (HSPG), laminin, and type IV collagen, during the development of hair follicles in late embryo rats. BPA...... of the elongating follicle. HSPG was associated with the basal cell layer prior to the appearance of hair follicle primordia and became BMZ-associated before birth but after follicle buds were first observed. HSPG was also found to be associated with the basal cell surfaces in the epidermis, but not in the hair...... follicle. Laminin and type IV collagen were continually present in epidermal and follicular BMZ both before and during development of hair follicles and were later present in the dermal papilla matrix. From these observations we conclude that (1) laminin and type IV collagen are functionally important...

  4. An unusual case of anti-glomerular basement membrane disease presenting with nephrotic syndrome. (United States)

    Okafor, Chidi C; Balogun, Rasheed A; Bourne, David T; Alhussain, Turki O; Abdel-Rahman, E M


    Anti-glomerular basement membrane (anti-GBM) disease is a vasculitic disease characterized by acute kidney injury, oliguria, hematuria and proteinuria. Proteinuria is rarely in the nephrotic range. A case of anti-GBM disease with proteinuria of 22.5 g/day is discussed. Immunofluorescence showed strong linear IgG deposits while electron microscopy showed widespread visceral epithelial cell foot cell process effacement. No electron dense immune complex-type deposits were identified. Pathology findings were not suggestive of simultaneous presentation of anti-GBM disease and other diseases associated with nephrotic range proteinuria. Anti-GBM disease should be considered in a comprehensive differential diagnosis of severe proteinuria.

  5. The bi-functional organization of human basement membranes. (United States)

    Halfter, Willi; Monnier, Christophe; Müller, David; Oertle, Philipp; Uechi, Guy; Balasubramani, Manimalha; Safi, Farhad; Lim, Roderick; Loparic, Marko; Henrich, Paul Bernhard


    The current basement membrane (BM) model proposes a single-layered extracellular matrix (ECM) sheet that is predominantly composed of laminins, collagen IVs and proteoglycans. The present data show that BM proteins and their domains are asymmetrically organized providing human BMs with side-specific properties: A) isolated human BMs roll up in a side-specific pattern, with the epithelial side facing outward and the stromal side inward. The rolling is independent of the curvature of the tissue from which the BMs were isolated. B) The epithelial side of BMs is twice as stiff as the stromal side, and C) epithelial cells adhere to the epithelial side of BMs only. Side-selective cell adhesion was also confirmed for BMs from mice and from chick embryos. We propose that the bi-functional organization of BMs is an inherent property of BMs and helps build the basic tissue architecture of metazoans with alternating epithelial and connective tissue layers.

  6. The bi-functional organization of human basement membranes.

    Directory of Open Access Journals (Sweden)

    Willi Halfter

    Full Text Available The current basement membrane (BM model proposes a single-layered extracellular matrix (ECM sheet that is predominantly composed of laminins, collagen IVs and proteoglycans. The present data show that BM proteins and their domains are asymmetrically organized providing human BMs with side-specific properties: A isolated human BMs roll up in a side-specific pattern, with the epithelial side facing outward and the stromal side inward. The rolling is independent of the curvature of the tissue from which the BMs were isolated. B The epithelial side of BMs is twice as stiff as the stromal side, and C epithelial cells adhere to the epithelial side of BMs only. Side-selective cell adhesion was also confirmed for BMs from mice and from chick embryos. We propose that the bi-functional organization of BMs is an inherent property of BMs and helps build the basic tissue architecture of metazoans with alternating epithelial and connective tissue layers.

  7. Laminin isoforms in endothelial and perivascular basement membranes. (United States)

    Yousif, Lema F; Di Russo, Jacopo; Sorokin, Lydia


    Laminins, one of the major functional components of basement membranes, are found underlying endothelium, and encasing pericytes and smooth muscle cells in the vessel wall. Depending on the type of blood vessel (capillary, venule, postcapillary venule, vein or artery) and their maturation state, both the endothelial and mural cell phenotype vary, with associated changes in laminin isoform expression. Laminins containing the α4 and α5 chains are the major isoforms found in the vessel wall, with the added contribution of laminin α2 in larger vessels. We here summarize current data on the precise localization of these laminin isoforms and their receptors in the different layers of the vessel wall, and their potential contribution to vascular homeostasis.

  8. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    Directory of Open Access Journals (Sweden)

    Aljona Gaiko-Shcherbak

    Full Text Available The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  9. Production of monoclonal antibodies to human glomerular basement membrane.

    Directory of Open Access Journals (Sweden)



    Full Text Available Using the technique of somatic cell fusion, we produced monoclonal antibodies to collagenase-digested human glomerular basement membrane (GBM. Fourteen monoclonal antibodies which reacted with normal human kidney in indirect immunofluorescence (IIF studies were produced. An analysis of the binding patterns indicated that the antigens recognized could be divided into six broad groups. Monoclonal antibody B3-H10 (Group 1 reacted with only GBM in a fine granular pattern. A5-B12 and B5-C2 (Group 2 reacted with GBM and peritubular capillary in a linear pattern. B2-A12 (Group 3 reacted with only epithelial cells. Al-C9 and A4-E2 (Group 4 showed a mesangial pattern in glomerulus and a lineal pattern in tubular basement membrane (TBM, Bowman's capsule and peritubular capillary. A1-E1, A1-E11, A2-E6, A3-B6, A4-F8 and B5-H2 (Group 5 recognized determinants common to GBM, TBM, Bowman's capsule and/or peritubular capillary. A3-F1 and B5-E10 (Group 6 reacted with TBM and Bowman's capsule. The staining pattern of B3-H10 (Group 1 was characteristic because it was not linear, but finely granular along the GBM. The staining pattern of B2-A12 (Group 3 was also characteristic because only epithelial cells were stained, and processes of epithelial cells were observed as fine fibrils. To the best of our knowledge, these two types of monoclonal antibodies have not been reported previously.

  10. The borderline: Basement membranes and the transition from premalignant to malignant neoplasia

    NARCIS (Netherlands)

    F.T.B. Bosman (Fré)


    textabstractIn this paper, the use of immunohistochemistry for the analysis of basement membrane components and related extracellular matrix proteins in human cancer is reviewed. Basement membranes in cancer are dynamic structures that are constantly degraded but also deposited, in close collaborati

  11. Enhanced assembly of basement membrane matrix by endodermal cells in response to fibronectin substrata

    DEFF Research Database (Denmark)

    Austria, M R; Couchman, J R


    Basement membranes are complex extracellular matrices contributing to the regulation of growth, migration and differentiation of many cell types. However, little is known about the mechanisms regulating the deposition and assembly of basement membrane from its constituents. We have investigated t...

  12. Basement membrane proteoglycans in glomerular morphogenesis: chondroitin sulfate proteoglycan is temporally and spatially restricted during development

    DEFF Research Database (Denmark)

    McCarthy, K J; Bynum, K; St John, P L;


    We previously reported the presence of a basement membrane-specific chondroitin sulfate proteoglycan (BM-CSPG) in basement membranes of almost all adult tissues. However, an exception to this ubiquitous distribution was found in the kidney, where BM-CSPG was absent from the glomerular capillary......, the present study used light and electron microscopic immunohistochemistry to examine the distribution of BM-CSPG and basement membrane heparan sulfate proteoglycan (BM-HSPG) during prenatal and postnatal renal development in the rat. Our results show that the temporal and spatial pattern of expression of BM...

  13. FOS-1 promotes basement-membrane removal during anchor-cell invasion in C. elegans. (United States)

    Sherwood, David R; Butler, James A; Kramer, James M; Sternberg, Paul W


    Cell invasion through basement membranes is crucial during morphogenesis and cancer metastasis. Here, we genetically dissect this process during anchor-cell invasion into the vulval epithelium in C. elegans. We have identified the fos transcription factor ortholog fos-1 as a critical regulator of basement-membrane removal. In fos-1 mutants, the gonadal anchor cell extends cellular processes normally toward vulval cells, but these processes fail to remove the basement membranes separating the gonad from the vulval epithelium. fos-1 is expressed in the anchor cell and controls invasion cell autonomously. We have identified ZMP-1, a membrane-type matrix metalloproteinase, CDH-3, a Fat-like protocadherin, and hemicentin, a fibulin family extracellular matrix protein, as transcriptional targets of FOS-1 that promote invasion. These results reveal a key genetic network that controls basement-membrane removal during cell invasion.

  14. Perlecan and basement membrane-chondroitin sulfate proteoglycan (bamacan) are two basement membrane chondroitin/dermatan sulfate proteoglycans in the Engelbreth-Holm-Swarm tumor matrix

    DEFF Research Database (Denmark)

    Couchman, J R; Kapoor, R; Sthanam, M;


    The presence of proteoglycans bearing galactosaminoglycan chains has been reported, but none has been identified previously in the matrix of the Engelbreth-Holm-Swarm tumor, which is a source of several basement membrane components. This tumor matrix contains perlecan, a large, low buoyant density...... heparan sulfate proteoglycan, widespread in many basement membranes and connective tissues. We now identify two distinct proteoglycan species from this tumor source, which are substituted with galactosaminoglycans and which show basement membrane localization by immunohistochemistry. One species...... is perlecan but, in addition to being present as a heparan sulfate proteoglycan, it is also present as a hybrid molecule, with dermatan sulfate chains. A minor population of perlecan apparently lacks heparan sulfate chains totally, and some of this is substituted with chondroitin sulfate. The second species...

  15. Anti-glomerular basement membrane disease superimposed on membranous nephropathy: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Nivera Noel


    Full Text Available Abstract Introduction Anti-glomerular basement membrane disease is a rare autoimmune disorder characterized by pulmonary hemorrhage, crescentic glomerulonephritis and the presence of circulating anti-glomerular basement membrane antibodies. The simultaneous occurrence of both anti-glomerular basement membrane disease and membranous nephropathy is rare. Case presentation A 59-year-old Hispanic man presented with acute onset of nausea and vomiting and was found to have renal insufficiency. Work-up included a kidney biopsy, which revealed anti-glomerular basement membrane disease with underlying membranous nephropathy. He was treated with emergent hemodialysis, intravenous corticosteroids, plasmapheresis, and cyclophosphamide without improvement in his renal function. Conclusion Simultaneous anti-glomerular basement membrane disease and membranous nephropathy is very rare. There have been 16 previous case reports in the English language literature that have been associated with a high mortality and morbidity, and a very high rate of renal failure resulting in hemodialysis. Co-existence of membranous nephropathy and anti-glomerular basement membrane disease may be immune-mediated, although the exact mechanism is not clear.

  16. Pericapillary basement membrane thickening in human skeletal muscles. (United States)

    Baum, Oliver; Bigler, Marius


    The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.

  17. Superficial dermal fibroblasts enhance basement membrane and epidermal barrier formation in tissue-engineered skin: implications for treatment of skin basement membrane disorders. (United States)

    Varkey, Mathew; Ding, Jie; Tredget, Edward E


    Basement membrane is a highly specialized structure that binds the dermis and the epidermis of the skin, and is mainly composed of laminins, nidogen, collagen types IV and VII, and the proteoglycans, collagen type XVIII and perlecan, all of which play critical roles in the function and resilience of skin. Both dermal fibroblasts and epidermal keratinocytes contribute to the development of the basement membrane, and in turn the basement membrane and underlying dermis influence the development and function of the epidermal barrier. Disruption of the basement membrane results in skin fragility, extensive painful blistering, and severe recurring wounds as seen in skin basement membrane disorders such as epidermolysis bullosa, a family of life-threatening congenital skin disorders. Currently, there are no successful strategies for treatment of these disorders; we propose the use of tissue-engineered skin as a promising approach for effective wound coverage and to enhance healing. Fibroblasts and keratinocytes isolated from superficial and deep dermis and epidermis, respectively, of tissue from abdominoplasty patients were independently cocultured on collagen-glycosaminoglycan matrices, and the resulting tissue-engineered skin was assessed for functional differences based on the underlying specific dermal fibroblast subpopulation. Tissue-engineered skin with superficial fibroblasts and keratinocytes formed a continuous epidermis with increased epidermal barrier function and expressed higher levels of epidermal proteins, keratin-5, and E-cadherin, compared to that with deep fibroblasts and keratinocytes, which had an intermittent epidermis. Further, tissue-engineered skin with superficial fibroblasts and keratinocytes formed better basement membrane, and produced more laminin-5, nidogen, collagen type VII, compared to that with deep fibroblasts and keratinocytes. Overall, our results demonstrate that tissue-engineered skin with superficial fibroblasts and keratinocytes

  18. Active Peptide-Conjugated Chitosan Matrices as an Artificial Basement Membrane

    Directory of Open Access Journals (Sweden)

    Kentaro Hozumi


    Full Text Available The basement membrane, a thin extracellular matrix, plays a critical role in tissue development and repair. Laminins are the major component of basement membrane and have diverse biological activities. We have identified various cell-adhesive peptides from laminins and their specific cell surface receptors. Polysaccharides, including chitosan, have been used as scaffolds, which regulate cellular functions for tissue engineering. We have developed laminin-derived active peptide-chitosan matrices as functional scaffolds. The biological activity of the peptides was enhanced when the peptides were conjugated to a chitosan matrix, suggesting that the peptide-chitosan matrix approach has an advantage for an active biomaterial. Further, the laminin peptide-chitosan matrices have the potential to mimic the basement membrane and are useful for tissue engineering as an artificial basement membrane.

  19. Distribution of basement membrane type IV collagen alpha chains in ameloblastoma: an immunofluorescence study


    Nakano, K.; Siar, C. H.; Nagai, N.; Naito, I.; Sado, Y.; Nagatsuka, H; Hoh, C; Kurada, K.; Tsujigiwa, H; M. Gunduz


    Background: Type IV collagen, a heterotrimeric molecule that exists in six genetically distinct forms, alpha1(IV)-alpha6(IV) is a major structural component of basement membrane (BM) and acts as a scaffold for other BM constituents. Methods: Indirect immunofluorescence using alpha chain-specific monoclonal antibodies was employed to clarify basement membrane (BM) collagen IV distribution in two ameloblastoma, and for comparison, on oral mucosa and tooth germ. Results: Ameloblastoma BM express...

  20. Anti-glomerular basement membrane glomerulonephritis and thrombotic microangiopathy in first degree relatives; a case report


    Idorn Thomas; Schejbel Lone; Rydahl Casper; Heaf James; Jølvig Karen; Bergstrøm Marie; Garred Peter; Kamper Anne-Lise


    Abstract Background Anti-glomerular basement membrane glomerulonephritis and thrombotic microangiopathy are rare diseases with no known coherence. Case Presentation A daughter and her biological mother were diagnosed with pregnancy-induced thrombotic microangiopathy and anti-glomerular basement membrane glomerulonephritis, respectively. Both developed end-stage renal disease. Exploration of a common aetiology included analyses of HLA genotypes, functional and genetic aspects of the complement...

  1. Expression of basement membrane components through morphological changes in the hair growth cycle

    DEFF Research Database (Denmark)

    Couchman, J R; Gibson, W T


    The amount and distribution of fibronectin associated with hair follicles was found to vary during the hair growth cycle in the rat. Immunocytochemical staining of follicles in mid-late anagen (the growth stage) revealed the presence of fibronectin in the dermal papilla matrix, in the basement...... membrane separating this from the epithelial cells of the hair bulb, and in the basement membrane and connective tissue sheath which underly the cells of the outer root sheath. Early in catagen, the transitional stage, staining of the dermal papilla matrix disappeared. Fibronectin persisted in the basement...

  2. Vascular basement membranes as pathways for the passage of fluid into and out of the brain. (United States)

    Morris, Alan W J; Sharp, Matthew MacGregor; Albargothy, Nazira J; Fernandes, Rute; Hawkes, Cheryl A; Verma, Ajay; Weller, Roy O; Carare, Roxana O


    In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

  3. Basement membrane chondroitin sulfate proteoglycan alterations in a rat model of polycystic kidney disease

    DEFF Research Database (Denmark)

    Ehara, T; Carone, F A; McCarthy, K J;


    Alterations in basement membrane components, notably proteoglycans, in a rat model of polycystic kidney disease have been investigated. Rats were fed phenol II (2-amino-4-hydroxyphenyl-5-phenyl thiazole) for 4 days and then changed to normal diet for a 7-day recovery period. Marked dilation...... of distal tubules and collecting ducts was observed by 4 days with phenol II treatment, but the morphology returned to normal after 7 days of subsequent normal diet. Staining of tissue sections with two mouse monoclonal antibodies to a recently described basement membrane chondroitin sulfate proteoglycan...... membrane heparan sulfate proteoglycan core protein related to perlecan did not diminish but rather stained affected tubules intensely, whereas laminin, on the other hand, was apparently diminished in the basement membranes of the cystic tubules. Type IV collagen staining did not change through disease...

  4. Entactin: ultrastructural localization of an ubiquitous basement membrane glycoprotein in mouse skin

    DEFF Research Database (Denmark)

    Horiguchi, Y; Fine, J D; Ljubimov, A V;


    Entactin is a recently described sulfated glycoprotein component of mouse endodermal cell-derived extracellular matrix and is present in a number of basement membranes. It has been ultrastructurally localized to both lamina densa and adjacent epithelial cell membranes in rodent kidney. In the pre...

  5. Molecular sieve of the rat glomerular basement membrane: a transmission electron microscopic study of enzyme-treated specimens.

    Directory of Open Access Journals (Sweden)



    Full Text Available Isolated rat glomerular basement membrane was treated with elastase and observed by transmission electron microscopy. The treatment with elastase revealed the fundamental structure of the glomerular basement membrane quite clearly, and enabled the observation of a sieve structure within the glomerular basement membrane. This sieve structure may play a major role in the filtration of blood as well as in the production of urine. Treatment with antibody showed that the sieve was mainly constituted of type IV collagen.

  6. Intercellular deposits of basement membrane material in active human pituitary adenomas detected by immunostaining for laminin and electron microscopy

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R


    Thirty-eight human pituitary adenomas (24 endocrine active and 14 endocrine inactive tumors) were studied immunohistochemically for the presence of the basement membrane component, laminin, and ultrastructurally for the presence of basement membrane. Immunoreactivity of laminin delineated staining...... of epithelial and endothelial basement membranes, the reaction product being confined mostly to the perivascular zones. Moreover, a hitherto undescribed presence of intercellular laminin-positive droplets was observed in ten of the active adenomas (nine patients with hyperprolactinemia and/or acromegalia...... matrix, indicating a mutual dependence between excessive hormone extrusion and an increase of "misplaced" deposits of basement membrane components, e.g., laminin....

  7. Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin

    DEFF Research Database (Denmark)

    Albrechtsen, R; Nielsen, M; Wewer, U


    The distribution of the basement membrane glycoprotein laminin was studied by the immunoperoxidase technique in benign and malignant human breast tissue and in axillary lymph nodes from patients with breast cancer. An antiserum prepared against rat laminin was used. The specificity of this antise......The distribution of the basement membrane glycoprotein laminin was studied by the immunoperoxidase technique in benign and malignant human breast tissue and in axillary lymph nodes from patients with breast cancer. An antiserum prepared against rat laminin was used. The specificity...... by laminin staining, but they were thinner and discontinuous. The poorly differentiated carcinomas lacked organized basement membranes detectable by laminin staining. Our studies suggest that staining for laminin may be a useful adjunct test for detection of micrometatases in lymph nodes. The correlation...

  8. Co-deposition of basement membrane components during the induction of murine splenic AA amyloid

    DEFF Research Database (Denmark)

    Lyon, A W; Narindrasorasak, S; Young, I D


    Past studies have demonstrated that during murine AA amyloid induction there is co-deposition of the AA amyloid peptide and the basement membrane form of heparan sulfate proteoglycan. The synthesis and accumulation of heparan sulfate proteoglycan does not usually occur in the absence of other bas...... enhancing factor induction of amyloid, the period when amyloid is first detected. These observations raise the possibility that an abnormality in basement membrane metabolism is a very early event, and potentially plays an integral part in the process of AA amyloidogenesis....

  9. Rat hair follicle dermal papillae have an extracellular matrix containing basement membrane components

    DEFF Research Database (Denmark)

    Couchman, J R


    Dermal papillae are small mesenchymally derived zones at the bases of hair follicles which have an important role in hair morphogenesis in the embryo and control of the hair growth cycle in postnatal mammals. The cells of the papilla are enmeshed in a dense extracellular matrix which undergoes...... extensive changes in concert with the hair cycle. Here it is shown that this matrix in anagen pelage follicles of postnatal rats contains an abundance of basement membrane components rather than dermal components such as interstitial collagens. In particular, type IV collagen, laminin, and basement membrane...

  10. Heterogeneous distribution of a basement membrane heparan sulfate proteoglycan in rat tissues

    DEFF Research Database (Denmark)

    Couchman, J R


    in immunohistochemical studies on frozen tissue sections from many rat organs. However, there was no reactivity with some basement membranes, notably those of several smooth muscle types and cardiac muscle. In addition, it was found that pancreatic acinar basement membranes also lacked the HSPG type recognized...... HSPG from the murine Engelbreth-Holm swarm tumor. It was, however, confirmed that only a single population of antibodies was present in the serum. Despite the presence of similar epitopes on these two proteoglycans of different hydrodynamic properties, it was apparent that the PYS-2 HSPG represents...

  11. Effects of radiation on the permeability of human basement membranes; Effets des radiations sur la permeabilite de membranes basales humaines

    Energy Technology Data Exchange (ETDEWEB)

    Fan, B.T. [Paris-7 Univ., ITODYS, UPRES-A 7086 CNRS, 75 (France); Achour, S. [Paris-7 Univ., 75 (France). Unite de Recheche Chimie et Pharmacologie; Simmonet, F. [CEA Saclay, 91 - Gif-sur-Yvette (France). INSTN, Institut National des Sciences et Techniques Nucleaires; Guerin, D. [Clinique d`Aulnay, 93 - Aulnay-sous-Bois (France)


    The influence of radiation on the permeability properties of human basement membrane was investigated by measuring the diffusion rate of several organic compounds (glycine, proline, glucose, urea and insulin) through human anterior lens capsules. The basement membranes borne an {gamma}-irradiation treatment change significantly their permeability vis-a-vis studied organic substances. This modification in physico-chemical properties is probably due to the radiation, which alters or degrades the complex structure (or architecture) of basement membranes. Moreover the change in permeability is dependent upon the diffusing compounds. An increase in diffusion has been observed for glucose, glycine and urea. However for insulin and proline, a decrease in diffusion rate was observed. (authors) 21 refs.

  12. Basement Membrane Mimics of Biofunctionalized Nanofibers for a Bipolar-Cultured Human Primary Alveolar-Capillary Barrier Model. (United States)

    Nishiguchi, Akihiro; Singh, Smriti; Wessling, Matthias; Kirkpatrick, Charles J; Möller, Martin


    In vitro reconstruction of an alveolar barrier for modeling normal lung functions and pathological events serve as reproducible, high-throughput pharmaceutical platforms for drug discovery, diagnosis, and regenerative medicine. Despite much effort, the reconstruction of organ-level alveolar barrier functions has failed due to the lack of structural similarity to the natural basement membrane, functionalization with specific ligands for alveolar cell function, the use of primary cells and biodegradability. Here we report a bipolar cultured alveolar-capillary barrier model of human primary cells supported by a basement membrane mimics of fully synthetic bifunctional nanofibers. One-step electrospinning process using a bioresorbable polyester and multifunctional star-shaped polyethylene glycols (sPEG) enables the fabrication of an ultrathin nanofiber mesh with interconnected pores. The nanofiber mesh possessed mechanical stability against cyclic expansion as seen in the lung in vivo. The sPEGs as an additive provide biofunctionality to fibers through the conjugation of peptide to the nanofibers and hydrophilization to prevent unspecific protein adsorption. Biofunctionalized nanofiber meshes facilitated bipolar cultivation of endothelial and epithelial cells with fundamental alveolar functionality and showed higher permeability for molecules compared to microporous films. This nanofiber mesh for a bipolar cultured barrier have the potential to promote growth of an organ-level barrier model for modeling pathological conditions and evaluating drug efficacy, environmental pollutants, and nanotoxicology.

  13. Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice. (United States)

    Krishnan, Meera R; Wang, Congmiao; Marion, Tony N


    The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane-binding anti-DNA antibody. Basement membrane-binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis.

  14. Drosophila laminins act as key regulators of basement membrane assembly and morphogenesis. (United States)

    Urbano, Jose M; Torgler, Catherine N; Molnar, Cristina; Tepass, Ulrich; López-Varea, Ana; Brown, Nicholas H; de Celis, Jose F; Martín-Bermudo, Maria D


    Laminins are heterotrimeric molecules found in all basement membranes. In mammals, they have been involved in diverse developmental processes, from gastrulation to tissue maintenance. The Drosophila genome encodes two laminin alpha chains, one beta and one Gamma, which form two distinct laminin trimers. So far, only mutations affecting one or other trimer have been analysed. In order to study embryonic development in the complete absence of laminins, we mutated the gene encoding the sole laminin beta chain in Drosophila, LanB1, so that no trimers can be made. We show that LanB1 mutant embryos develop until the end of embryogenesis. Electron microscopy analysis of mutant embryos reveals that the basement membranes are absent and the remaining extracellular material appears disorganised and diffuse. Accordingly, abnormal accumulation of major basement membrane components, such as Collagen IV and Perlecan, is observed in mutant tissues. In addition, we show that elimination of LanB1 prevents the normal morphogenesis of most organs and tissues, including the gut, trachea, muscles and nervous system. In spite of the above structural roles for laminins, our results unravel novel functions in cell adhesion, migration and rearrangement. We propose that while an early function of laminins in gastrulation is not conserved in Drosophila and mammals, their function in basement membrane assembly and organogenesis seems to be maintained throughout evolution.

  15. Macrophage Chemotaxis in Anti-tubular Basement Membrane-Induced Interstitial Nephritis in Guinea Pigs

    NARCIS (Netherlands)

    Kennedy, Thomas L.; Merrow, Martha; Phillips, S. Michael; Norman, Michael; Neilson, Eric G.


    Interstitial renal lesions containing T cells and macrophages develop after 14 days in guinea pigs immunized to produce anti-tubular basement membrane-induced interstitial nephritis. We serially examined the renal venous and systemic arterial sera from such animals to determine if chemotactic factor

  16. Peroxynitrous acid induces structural and functional modifications to basement membranes and its key component, laminin

    DEFF Research Database (Denmark)

    Degendorfer, Georg; Chuang, Christine Y.; Hammer, Astrid;


    Basement membranes (BM) are specialized extracellular matrices underlying endothelial cells in the artery wall. Laminin, the most abundant BM glycoprotein, is a structural and biologically active component. Peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent, is formed in vivo at s...

  17. Cdc42 expression in keratinocytes is required for the maintenance of the basement membrane in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Brakebusch, Cord


    , structure and number of hemidesomosomes were not significantly changed in the Cdc42 mutant skin compared with the control mice and no blister formation was observed in mutant skin. These data indicate that Cdc42 in keratinocytes is important for maintenance of the basement membrane of skin....

  18. Ultrastructure of basement membranes in monkey and shark teeth at an early stage of development. (United States)

    Sawada, Takashi


    The basement membrane, which separates the inner enamel epithelium from the dental papilla in the early stages of tooth development, is known to play a significant role in odontogenesis. In this review article, this basement membrane was described in detail based on our recent findings with the use of high-resolution electron microscopy. Tooth germs of a monkey (Macaca fuscata) and a shark (Cephaloscyllium umbratile) were processed for thin-section observations. During the early stage of development, the basement membrane of the inner enamel (dental) epithelium was composed of a lamina lucida, lamina densa, and much wider lamina fibroreticularis. At higher magnification, the lamina densa in both species was made up of a fine network of cords, which are generally the main constituents of the basement membranes. In the monkey tooth, the lamina fibroreticularis was rich in fibrils, which were now characterized as basotubules, 10-nm-wide microfibril-like structures. The space between the basotubules was filled with a cord network that extended from the lamina densa. Dental papilla cell processes were inserted into the lamina fibroreticularis, and their surface was closely associated with numerous parallel basotubules via 1.5- to 3-nm-wide filaments. In the shark tooth during its early stage of development, the basotubules were absent in the lamina fibroreticularis and only narrow extensions, 60-90 nm wide and 1-2 microm long, of the cord network of the lamina densa were present. The dental papilla cells were immobilized by means of the binding of their processes to the extensions. These results indicate that basement membranes in both monkey and shark teeth at early stage of development are specialized for functions as anchoring and firm binding, which are essential for the successful differentiation of the odontoblasts.

  19. Hypoplastic basement membrane of the lens anlage in the inheritable lens aplastic mouse (lap mouse). (United States)

    Aso, S; Baba, R; Noda, S; Ikuno, S; Fujita, M


    Adult homozygous lap mice show various eye abnormalities such as aphakia, retinal disorganization, and dysplasia of the cornea and anterior chamber. In the fetal eye of a homozygous lap mouse, the lens placode appears to develop normally. However, the lens vesicle develops abnormally to form a mass of cells without a cavity, and the mass vanishes soon afterward. Apoptotic cell death is associated with the disappearance of the lens anlage. We examined the basement membranes of the lens anlage of this mutant by immunohistochemical methods under light microscopy using antibodies against basement membrane components of the lens anlage, type IV collagen, fibronectin, laminin, heparan sulfate proteoglycan, and entactin and by transmission electron microscopy. Immunohistochemistry showed the distribution and intensity of antibody binding to the lens anlage to be almost the same for each these antibodies regardless of the stage of gestation or whether the anlagen were from normal BALB/c or lap mice. Thus, positive continuous reactions were observed around the exterior region of the lens anlage from day 10 of gestation for type IV collagen, fibronectin, laminin, heparan sulfate proteoglycan antibodies, and at least from day 11of gestation for entactin antibody. The basement membrane lamina densa of both normal and lap mice was shown by electron microscopy to be discontinuous at days 10 and 10.5 of gestation. However, by day 11 the lamina densa was continuous in the lens anlagen of normal mice but still discontinuous in the lap mice. By day 12 of gestation, the lamina densa had thickened markedly in normal mice, whereas in lap mice it remained discontinuous and its thinness indicated hypoplasia. These results indicate that, while all basement components examined are produced and deposited in the normal region of the lens anlage in the lap mouse, the basement membrane is, for some reason, imperfectly formed. The time at which hypoplasia of the basement membrane was observed

  20. Basement membrane abnormalities in human eyes with diabetic retinopathy

    DEFF Research Database (Denmark)

    Ljubimov, A V; Burgeson, R E; Butkowski, R J


    discontinuously for laminin-1, entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR corneas. Major BM alterations were found in DR retinas compared to normals and non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had accumulations of fibronectin (including cellular......) and Types I, III, IV (alpha1-alpha2), and V collagen. The BM zone of new retinal blood vessels in neovascularized areas accumulated tenascin and Type XII collagen, whereas normal, diabetic, and adjacent DR retinas showed only weak and irregular staining. In preretinal membranes, perlecan, bamacan, and Types...... VI, VIII, XII, and XIV collagen were newly identified. Diabetic BM thickening appears to involve qualitative alterations of specific BM markers at an advanced disease stage, with the appearance of DR....

  1. In vivo laser confocal microscopy findings in patients with map-dot-fingerprint (epithelial basement membrane dystrophy

    Directory of Open Access Journals (Sweden)

    Kobayashi A


    Full Text Available Akira Kobayashi, Hideaki Yokogawa, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: The purpose of this study was to investigate pathological changes of the corneal cell layer in patients with map-dot-fingerprint (epithelial basement membrane dystrophy by in vivo laser corneal confocal microscopy.Methods: Two patients were evaluated using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM. The affected corneal areas of both patients were examined. Image analysis was performed to identify corneal epithelial and stromal deposits correlated with this dystrophy.Results: Variously shaped (linear, multilaminar, curvilinear, ring-shape, geographic highly reflective materials were observed in the “map” area, mainly in the basal epithelial cell layer. In “fingerprint” lesions, multiple linear and curvilinear hyporeflective lines were observed. Additionally, in the affected corneas, infiltration of possible Langerhans cells and other inflammatory cells was observed as highly reflective Langerhans cell-like or dot images. Finally, needle-shaped materials were observed in one patient.Conclusion: HRT 2-RCM laser confocal microscopy is capable of identifying corneal microstructural changes related to map-dot-fingerprint corneal dystrophy in vivo. The technique may be useful in elucidating the pathogenesis and natural course of map-dot-fingerprint corneal dystrophy and other similar basement membrane abnormalities.Keywords: cornea, confocal microscopy, map-dot-fingerprint dystrophy, epithelial basement membrane dystrophy, Heidelberg Retina Tomograph 2 Rostock Cornea Module (HRT 2-RCM

  2. Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea

    Directory of Open Access Journals (Sweden)

    Koon-Ja Lee


    Full Text Available To understand the corneal regeneration induced by bevacizumab,we investigated the structure changes of stroma andbasement membrane regeneration. A Stick soaked in 0.5 NNaOH onto the mouse cornea and 2.5 mg/ml of bevacizumabwas delivered into an alkali-burned cornea (2 μl by subconjunctivalinjections at 1 hour and 4 days after injury. At 7 daysafter injury, basement membrane regeneration was observedby transmission electron microscope. Uneven and thin epithelialbasement membrane, light density of hemidesmosomes,and edematous collagen fibril bundles are shown in thealkali-burned cornea. Injured epithelial basement membraneand hemidesmosomes and edematous collagen fibril bundlesresulting from alkali-burned mouse cornea was repaired bybevacizumab treatment. This study demonstrates that bevacizumabcan play an important role in wound healing in thecornea by accelerating the reestablishment of basementmembrane integrity that leads to barriers for scar formation.[BMB Reports 2013; 46(4: 195-200

  3. The effect of asthma on the perimeter of the airway basement membrane. (United States)

    Elliot, John G; Budgeon, Charley A; Harji, Salima; Jones, Robyn L; James, Alan L; Green, Francis H


    When comparing the pathology of airways in individuals with and without asthma, the perimeter of the basement membrane (Pbm) is used as a marker of airway size, as it is independent of airway smooth muscle shortening or airway collapse. The extent to which the Pbm is itself altered in asthma has not been quantified. The aim of this study was to compare the Pbm from the same anatomical sites in postmortem lungs from subjects with (n = 55) and without (n = 30) asthma (nonfatal or fatal). Large and small airways were systematically sampled at equidistant "levels" from the apical segment of the left upper lobes and anterior and basal segments of the left lower lobes of lungs fixed in inflation. The length of the Pbm was estimated from cross sections of airway at each relative level. Linear mixed models were used to investigate the relationships between Pbm and sex, age, height, smoking status, airway level, and asthma group. The final model showed significant interactions between Pbm and airway level in small (<3 mm) airways, in subjects having asthma (P < 0.0001), and by sex (P < 0.0001). No significant interactions for Pbm between asthma groups were observed for larger airways (equivalent to a diameter of ∼3 mm and greater) or smoking status. Asthma is not associated with remodeling of the Pbm in large airways. In medium and small airways, the decrease in Pbm in asthma (≤20%) would not account for the published differences in wall area or area of smooth muscle observed in cases of severe asthma.

  4. Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies

    DEFF Research Database (Denmark)

    Ljubimov, A V; Bartek, J; Couchman, J R


    -membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated...... by the presence of fibrillar deposits of basement-membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement...

  5. Heparan sulfate proteoglycans made by different basement-membrane-producing tumors have immunological and structural similarities

    DEFF Research Database (Denmark)

    Wewer, U M; Albrechtsen, R; Hassell, J R


    Using immunological assays, we determined the relationship between the heparan sulfate proteoglycans produced by two different murine basement-membrane-producing tumors, i.e., the mouse Engelbreth-Holm-Swarm (EHS) tumor and the L2 rat yolk-sac tumor. Antibodies prepared against the heparan sulfate...... mainly heparan sulfate (75%) along with smaller amounts of chondroitin sulfate (19%), whereas the L2 rat yolk-sac tumor produced mainly chondroitin sulfate (76%) with smaller amounts of heparan sulfate (21%). We conclude that these two murine basement-membrane-producing tumors elaborate...... proteoglycans obtained from these two sources immunoprecipitated the same precursor protein with a molecular mass of 400,000 daltons from 35S-methionine pulse-labeled cells of both tumors. Immunohistochemistry showed the heparan sulfate proteoglycan to be distributed in the extracellular matrix and also...

  6. VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during Retinal Sprouting Angiogenesis

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    Pirjo Spuul


    Full Text Available During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically.

  7. Tissue fibrocytes in patients with mild asthma: A possible link to thickness of reticular basement membrane?

    Directory of Open Access Journals (Sweden)

    Bjermer Leif


    Full Text Available Abstract Background Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. We have studied the correlation of tissue fibrocyte levels to basement membrane thickness and the presence of fibrocytes in bronchoalveolar lavage fluid (BALF in steroid-naive patients with mild asthma and controls. Methods Patients with mild asthma (n = 9 were recruited and divided into two categories based on whether or not fibroblast-like cells could be established from BALF. Non-asthmatic healthy subjects (n = 5 were used as controls. Colocalization of the fibrocyte markers CD34, CD45RO, procollagen I, and α-smooth muscle actin (α-SMA were identified in bronchial biopsies from patients and controls by confocal microscopy. Kruskall-Wallis method was used to calculate statistical significance and Spearman coefficient of rank correlation was used to assess the degree of association. Results In patients with BALF fibroblasts, a 14-fold increase of tissue cells expressing CD34/CD45RO/α-SMA and a 16-fold increase of tissue cells expressing CD34/procollagen I was observed when compared to controls (p Conclusion These findings indicate a correlation between recruited fibrocytes in tissue and thickness of basement membrane. Fibroblast progenitor cells may therefore be important in airway remodeling in steroid-naive patients with mild asthma.

  8. Regeneration of the epidermis and basement membrane of the planarian Dugesia japonica after total-body x irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hori, I.


    Fresh-water planarians were studied to examine effects of x rays on regeneration of the epidermis and basement membrane. During early stages of regeneration, free rhabdite-forming cells were associated with the wound epidermis and recruited it. In later stages, however, a gradual degeneration occurred in the epidermis and cells undergoing epithelization decreased in number. Eventually epidermal cells on the wound surface appeared necrotic as evidenced by pyknotic nuclei and vacuolized dense cytoplasm. The entire basement membrane could not be reconstituted in any stage after wounding though its precursor-like material was secreted in the interspace between epidermis and parenchyma. Morphological changes in extracellular products and in the cells surrounding the products suggest that epidermal cells which have covered the wound surface synthesize precursors of the basement membrane. Possible factors of a characteristic perturbation in epithelization and basement membrane formation after total-body irradiation are discussed.

  9. Human skin basement membrane-associated heparan sulphate proteoglycan: distinctive differences in ultrastructural localization as a function of developmental age

    DEFF Research Database (Denmark)

    Horiguchi, Y; Fine, J D; Couchman, J R


    Recent studies have demonstrated that skin basement membrane components are expressed within the dermo-epidermal junction in an orderly sequence during human foetal development. We have investigated the ultrastructural localization of basement membrane-related antigens in human foetal skin...... was identical to that observed in neonatal and adult human skin. These findings demonstrate that active remodelling of the dermo-epidermal junction occurs during at least the first two trimesters, and affects not only basement membrane-associated structures but also specific antigens....... at different developmental ages using two monoclonal antibodies to a well-characterized basement membrane-associated heparan sulphate proteoglycan. A series of foetal skin specimens (range, 54-142 gestational days) were examined using an immunoperoxidase immunoelectron microscopic technique. In specimens...

  10. Type XV collagen in human colonic adenocarcinomas has a different distribution than other basement membrane zone proteins. (United States)

    Amenta, P S; Briggs, K; Xu, K; Gamboa, E; Jukkola, A F; Li, D; Myers, J C


    In situ carcinomas must penetrate their own basement membrane to be classified as invasive, and subsequently infiltrate surrounding connective tissue and cross vascular basement membranes to metastasize hematogenously. Accordingly, in many studies, integral basement membrane components, including type IV collagen, laminin, and heparan sulfate proteoglycan, have been localized in a spectrum of tumors to gain insight into their role in neoplasia. A number of recently identified extracellular matrix molecules and isoforms of the aforementioned proteins have been localized to the basement membrane zone, illustrating another level of biochemical heterogeneity in these structures. As the complexity of these matrices becomes more apparent, their roles in maintaining homeostasis and in tumor biology falls into question. Of the new group of collagens localized to the basement membrane zone, type XV was the first to be characterized (Cell Tissue Res, 286:493-505, 1996). This nonfibrillar collagen has a nearly ubiquitous distribution in normal human tissues via a strong association with basement membrane zones, suggesting that it functions to adhere basement membrane to the underlying stroma. To begin investigation of this protein in malignant tumors, we have localized type XV in human colonic adenocarcinomas and compared its distribution with that of type IV collagen and laminin. Collagens XV and IV and laminin were found in all normal and colonic epithelial, muscle, fat, neural, and vascular basement membrane zones, as shown previously. In moderately differentiated, invasive adenocarcinomas, laminin and type IV collagen were sometimes observed as continuous, linear deposits around some of the malignant glands, but more often they were seen in either discontinuous deposits or were completely absent. In contrast, type XV collagen was characterized as virtually absent from the basement membrane zones of malignant glandular elements in moderately differentiated tumors

  11. Pathological changes waterproof membranes and their identification

    Directory of Open Access Journals (Sweden)

    Novotný Marek


    Full Text Available With the development of waterproofing systems based on synthetic membranes, especially mPVC, there is an increase in pathological changes of these membranes. Competing manufacturers and pressure on price of the final product have resulted in usage of unstable or low quality raw materials. After production, these materials keep their specific characteristics, however, their aging is accelerated, i.e. they lose their essential qualitative characteristics very quickly. Very important is the detection of these processes which is possible using chemical analysis (gas chromatography, IR analysis and others as well as using visual inspection of surface by microscope, including 3D modeling. Very important are weldability tests which identify glass transition temperature of the material. The results can then be used as a basis for correct identification of problems with weldability, nonweldability of synthetic membranes, respectively, as well as for identification of normal or abnormal aging of these materials.

  12. Scaffold-forming and Adhesive Contributions of Synthetic Laminin-binding Proteins to Basement Membrane Assembly. (United States)

    McKee, Karen K; Capizzi, Stephanie; Yurchenco, Peter D


    Laminins that possess three short arms contribute to basement membrane assembly by anchoring to cell surfaces, polymerizing, and binding to nidogen and collagen IV. Although laminins containing the alpha4 and alpha5 subunits are expressed in alpha2-deficient congenital muscular dystrophy, they may be ineffective substitutes because they bind weakly to cell surfaces and/or because they lack the third arm needed for polymerization. We asked whether linker proteins engineered to bind to deficient laminins that provide such missing activities would promote basement membrane assembly in a Schwann cell model. A chimeric fusion protein (alphaLNNd) that adds a short arm terminus to laminin through the nidogen binding locus was generated and compared with the dystrophy-ameliorating protein miniagrin (mAgrin) that binds to the laminin coiled-coil dystroglycan and sulfatides. alphaLNNd was found to mediate laminin binding to collagen IV, to bind to galactosyl sulfatide, and to selectively convert alpha-short arm deletion-mutant laminins LmDeltaalphaLN and LmDeltaalphaLN-L4b into polymerizing laminins. This protein enabled polymerization-deficient laminin but not an adhesion-deficient laminin lacking LG domains (LmDeltaLG) to assemble an extracellular matrix on Schwann cell surfaces. mAgrin, on the other hand, enabled LmDeltaLG to form an extracellular matrix on cell surfaces without increasing accumulation of non-polymerizing laminins. These gain-of-function studies reveal distinct polymerization and anchorage contributions to basement membrane assembly in which the three different LN domains mediate the former, and the LG domains provide primary anchorage with secondary contributions from the alphaLN domain. These findings may be relevant for an understanding of the pathogenesis and treatment of laminin deficiency states.

  13. Basement membrane heparan sulfate proteoglycan from the L2 rat yolk sac carcinoma

    DEFF Research Database (Denmark)

    Fenger, M; Wewer, U; Albrechtsen, R


    Heparan sulfate proteoglycan from the L2 rat yolk sac carcinoma has been purified and partially characterized. The proteoglycan has an apparent Mr of 750 000, 35% of which represents the core protein. The core protein seems to be homogeneous, whereas the heparan sulfate chains are heterogeneous w...... with an Mr of about 50 000-70 000, with 30% of the glucosamine being N-sulfated. Antibodies raised against the core protein of the heparan sulfate proteoglycan reacted with basement membranes of various rat and human tissue....

  14. Basement membrane heparan sulfate proteoglycan from the L2 rat yolk sac carcinoma

    DEFF Research Database (Denmark)

    Fenger, M; Wewer, U; Albrechtsen, R


    Heparan sulfate proteoglycan from the L2 rat yolk sac carcinoma has been purified and partially characterized. The proteoglycan has an apparent Mr of 750 000, 35% of which represents the core protein. The core protein seems to be homogeneous, whereas the heparan sulfate chains are heterogeneous...... with an Mr of about 50 000-70 000, with 30% of the glucosamine being N-sulfated. Antibodies raised against the core protein of the heparan sulfate proteoglycan reacted with basement membranes of various rat and human tissue....

  15. Anti-glomerular basement membrane glomerulonephritis and thrombotic microangiopathy in first degree relatives; a case report

    Directory of Open Access Journals (Sweden)

    Idorn Thomas


    Full Text Available Abstract Background Anti-glomerular basement membrane glomerulonephritis and thrombotic microangiopathy are rare diseases with no known coherence. Case Presentation A daughter and her biological mother were diagnosed with pregnancy-induced thrombotic microangiopathy and anti-glomerular basement membrane glomerulonephritis, respectively. Both developed end-stage renal disease. Exploration of a common aetiology included analyses of HLA genotypes, functional and genetic aspects of the complement system, ADAMTS13 activity and screening for autoantibodies. The daughter was heterozygous carrier of the complement factor I G261D mutation, previously described in patients with membranoproliferative glomerulonephritis and atypical haemolytic uremic syndrome. The mother was non-carrier of this mutation. They shared the disease associated complement factor H silent polymorphism Q672Q (79602A>G. Conclusion An unequivocal functional or molecular association between these two family cases was not found suggesting that the patients probably share another, so far undiagnosed and unknown, predisposing factor. It seems highly unlikely that two infrequent immunologic diseases would occur by unrelated pathophysiological mechanisms within first degree relatives.

  16. Mechanical Stretch on Human Skin Equivalents Increases the Epidermal Thickness and Develops the Basement Membrane.

    Directory of Open Access Journals (Sweden)

    Eijiro Tokuyama

    Full Text Available All previous reports concerning the effect of stretch on cultured skin cells dealt with experiments on epidermal keratinocytes or dermal fibroblasts alone. The aim of the present study was to develop a system that allows application of stretch stimuli to human skin equivalents (HSEs, prepared by coculturing of these two types of cells. In addition, this study aimed to analyze the effect of a stretch on keratinization of the epidermis and on the basement membrane. HSEs were prepared in a gutter-like structure created with a porous silicone sheet in a silicone chamber. After 5-day stimulation with stretching, HSEs were analyzed histologically and immunohistologically. Stretch-stimulated HSEs had a thicker epidermal layer and expressed significantly greater levels of laminin 5 and collagen IV/VII in the basal layer compared with HSEs not subjected to stretch stimulation. Transmission electron microscopy revealed that the structure of the basement membrane was more developed in HSEs subjected to stretching. Our model may be relevant for extrapolating the effect of a stretch on the skin in a state similar to an in vivo system. This experimental system may be useful for analysis of the effects of stretch stimuli on skin properties and wound healing and is also expected to be applicable to an in vitro model of a hypertrophic scar in the future.

  17. Validation of glomerular basement membrane thickness changes with aging in minimal change disease. (United States)

    Sato, Shigeru; Sasaki, Yoshihiro; Adachi, Akiko; Ghazizadeh, Mohammad


    Measurement of the normal range of glomerular basement membrane (GBM) thickness by electron microscopy is required for the diagnosis of thin basement membrane disease or diabetic nephropathy; however, this measurement is influenced by aging. The aim of this study was to introduce a simple histogram plotting method for the validation of the results of the GBM thickness measurements by the accepted arithmetic mean ± SD method. We examined renal biopsy specimens obtained from 19 patients (10 males and 9 females) with minimal change disease, ranging in age from 3 to 70 years. Renal tissue samples obtained at autopsy from a male baby (3 months old) with no renal disease were also examined. For each case, GBM thicknesses at 10-15 evenly distributed points per glomerular loop were directly measured and the arithmetic mean ± SD was calculated. Subsequently, the arithmetic mean ± SD for each group of cases classified by age into 4 groups, i.e. babyhood (3 months old), childhood (3-11 years old), adulthood (12-57 years old), and old age (60-70 years old), was determined. On the other hand, a histogram of the frequency of GBM points measured against thickness was plotted to determine the distribution pattern and the range of measurements in each age group. The histogram plot showed 4 clearly divided modes for GBM thickness. Comparison of the results obtained by the 2 methods revealed a significant correlation indicating the feasibility of the histogram plotting method as a useful adjunct to validate GBM thickness measurements.

  18. Nephritogenic lupus antibodies recognize glomerular basement membrane-associated chromatin fragments released from apoptotic intraglomerular cells. (United States)

    Kalaaji, Manar; Mortensen, Elin; Jørgensen, Leif; Olsen, Randi; Rekvig, Ole Petter


    Antibodies to dsDNA represent a classification criterion for systemic lupus erythematosus. Subpopulations of these antibodies are involved in lupus nephritis. No known marker separates nephritogenic from non-nephritogenic anti-dsDNA antibodies. It is not clear whether specificity for glomerular target antigens or intrinsic antibody-affinity for dsDNA or nucleosomes is a critical parameter. Furthermore, it is still controversial whether glomerular target antigen(s) is constituted by nucleosomes or by non-nucleosomal glomerular structures. Previously, we have demonstrated that antibodies eluted from murine nephritic kidneys recognize nucleosomes, but not other glomerular antigens. In this study, we determined the structures that bind nephritogenic autoantibodies in vivo by transmission electron microscopy, immune electron microscopy, and colocalization immune electron microscopy using experimental antibodies to dsDNA, to histones and transcription factors, or to laminin. The data obtained are consistent and point at glomerular basement membrane-associated nucleosomes as target structures for the nephritogenic autoantibodies. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling or caspase-3 assays demonstrate that lupus nephritis is linked to intraglomerular cell apoptosis. The data suggest that nucleosomes are released by apoptosis and associate with glomerulus basement membranes, which may then be targeted by pathogenic anti-nucleosome antibodies. Thus, apoptotic nucleosomes may represent both inducer and target structures for nephritogenic autoantibodies in systemic lupus erythematosus.

  19. Association of anti-glomerular basement membrane antibody disease with dermatomyositis and psoriasis: case report

    Directory of Open Access Journals (Sweden)

    Natália Pereira Machado

    Full Text Available CONTEXT: Anti-glomerular basement membrane (anti-GBM antibody syndrome is characterized by deposition of anti-GBM antibodies on affected tissues, associated with glomerulonephritis and/or pulmonary involvement. This syndrome has been described in association with other autoimmune disorders, but as far as we know, it has not been described in association with dermatomyositis and psoriasis. CASE REPORT: A 51-year-old man with a history of dermatomyositis and vulgar psoriasis presented with a condition of sensitive-motor polyneuropathy of the hands and feet, weight loss of 4 kg, malaise and fever. On admission, he had been making chronic use of cyclosporin and antihypertensive drugs for three months because of mild arterial hypertension. Laboratory tests showed anemia and leukocytosis, elevated serum urea and creatinine and urine presenting proteinuria, hematuria, leukocyturia and granular casts. The 24-hour proteinuria was 2.3 g. Renal biopsy showed crescentic necrotizing glomerulonephritis with linear immunoglobulin G (IgG deposits on the glomerular basement membrane by means of direct immunofluorescence, which were suggestive of anti-GBM antibodies. The patient was then treated initially with methylprednisolone and with monthly cyclophosphamide in the form of pulse therapy.

  20. Isolation and partial characterization of antigens from basement membranes and streptococcal cell membrane (SCM) employing anti-SCM monoclonal antibody. (United States)

    Zelman, M E; Lange, C F


    Monoclonal antibodies (mAb) against streptococcal cell membrane (SCM) antigen were used to identify specific cross-reactive peptides prepared by trypsin digestion of purified glomerular basement membrane (GBM) and lung basement membrane (LBM). Anti-SCM mAb-coupled HPLC columns were used to affinity isolate soluble LBM, GBM, and SCM antigens which then were sized by HPLC. Alternatively, SCM, GBM, and LBM digests were subjected to an initial separation by HPLC into component polypeptides, followed by affinity purification and ELISA of these fractions using anti-SCM mAb. Comparison of the antigenic reactivities by ELISA of the sized polypeptides on a nanomolar basis permitted the estimation of their individual relative epitope densities. The results for SCM antigens showed increasing epitope density with increasing molecular size, which suggests that intact SCM consists of repeating epitopes. Low mol. wt GBM polypeptides in nanogram amounts inhibited mAb binding to SCM, indicating that these small GBM polypeptides may similarly contain more than a single cross-reactive epitope. The identification of these cross-reactive epitopes in LBM and GBM has important implications for the etiology of post-streptococcal sequelae.

  1. Laminin, a noncollagenous component of epithelial basement membranes synthesized by a rat yolk sac tumor

    DEFF Research Database (Denmark)

    Wewer, U; Albrechtsen, R; Ruoslahti, E


    Laminin, a glycoprotein antigenically similar or identical to a component of epithelial basement membranes, was identified as a major component of the abundant extracellular matrix synthesized by an experimentally induced rat yolk sac tumor. Immunocytochemical staining revealed laminin in cultured...... polypeptides with molecular weights of approximately 200,000 and 400,000. These comigrated with the polypeptides of mouse laminin isolated previously. The yolk sac tumor tissue grown in vivo contained laminin in the tumor cells and in the extracellular material as evidenced by immunofluorescence...... membranes in rat tissues in a manner indistinguishable from antilaminin. The presence of laminin in rat yolk sac cells, the presumed origin of our yolk sac tumor, was studied in some detail. Laminin was found to be present in normal cells of the visceral as well as the parietal yolk sac layer...

  2. Rat mesangial cells in vitro synthesize a spectrum of proteoglycan species including those of the basement membrane and interstitium

    DEFF Research Database (Denmark)

    Thomas, G J; Shewring, L; McCarthy, K J;


    Accumulation of extracellular matrix within the mesangium is an important event in the development of glomerular disease. In this report we have used indirect immunofluorescence to positively identify a number of constituents of the mesangial matrix synthesized by rat mesangial cells (RMC) in vitro...... including laminin, fibronectin, type IV collagen and the basement membrane heparan sulphate proteoglycan (BM-HSPG) known as perlecan. In addition, using Mab 2B5 we demonstrate that RMC synthesize a specific basement membrane chondroitin sulfate (BM-CSPG), a matrix component that in normal animals...... is localized in the mesangium but is not found in the pericapillary glomerular basement membrane (GBM). Further characterization of the proteoglycans synthesized by RMC in vitro revealed: (i) a second large CSPG, identified as versican; (ii) two small dermatan sulphate proteoglycans identified as biglycan...

  3. Breaches of the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies. (United States)

    Li, Jing; Yu, Miao; Feng, Gang; Hu, Huaiyu; Li, Xiaofeng


    A subset of congenital muscular dystrophies (CMDs) has central nervous system manifestations. There are good mouse models for these CMDs that include POMGnT1 knockout, POMT2 knockout and Large(myd) mice with all exhibiting defects in dentate gyrus. It is not known how the abnormal dentate gyrus is formed during the development. In this study, we conducted a detailed morphological examination of the dentate gyrus in adult and newborn POMGnT1 knockout, POMT2 knockout, and Large(myd) mice by immunofluorescence staining and electron microscopic analyses. We observed that the pial basement membrane overlying the dentate gyrus was disrupted and there was ectopia of granule cell precursors through the breached pial basement membrane. Besides these, the knockout dentate gyrus exhibited reactive gliosis in these mouse models. Thus, breaches in the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies.

  4. Three-dimensional architecture of rat glomerular basement membrane by ultra-high resolution scanning electron microscopy.

    Directory of Open Access Journals (Sweden)



    Full Text Available We demonstrated the ultrastructure of rat glomerular basement membrane (GBM by ultra-high resolution scanning electron microscopy. GBM prepared by sonication methods and conductive-staining could be observed without metal coating at magnifications as high as 400,000 times. The GBM showed an irregular meshwork structure composed of various strands and pores. The width of the strands ranged from 6 to 15 nm, and the diameter of pores ranged from 6 to 50 nm. The present study confirmed our molecular sieve theory of the basement membrane.

  5. Antiglomerular basement membrane antibody-mediated glomerulonephritis after intranasal cocaine use. (United States)

    Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J


    We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.

  6. Cell invasion through basement membrane: the anchor cell breaches the barrier. (United States)

    Hagedorn, Elliott J; Sherwood, David R


    Cell invasion through basement membrane (BM) is a specialized cellular behavior critical to many normal developmental events, immune surveillance, and cancer metastasis. A highly dynamic process, cell invasion involves a complex interplay between cell-intrinsic elements that promote the invasive phenotype, and cell-cell and cell-BM interactions that regulate the timing and targeting of BM transmigration. The intricate nature of these interactions has made it challenging to study cell invasion in vivo and model in vitro. Anchor cell invasion in Caenorhabditis elegans is emerging as an important experimental paradigm for comprehensive analysis of BM invasion, revealing the gene networks that specify invasive behavior and the interactions that occur at the cell-BM interface.

  7. Transplacental transmission of antibodies to tubular basement membrane in guinea-pigs with autoimmune tubulointerstitial nephritis. (United States)

    Albini, B; Milgrom, M; Noble, B; Albini, C; Ossi, E; Andres, G A


    The offspring of female guinea-pigs with tubulo-interstitial nephritis were studied for possible passive transfer of disease. Whereas no immune deposits were seen on or before day 30 of gestation, IgG was detected in the tubular basement membrane (TBM) of fetuses at and after day 44. Serum of offspring contained antibodies to TBM, albeit in much lower titres than found in circulation of the mother guinea-pigs. No histopathological changes were seen in fetal kidneys. Thus, autoantibodies induced by heteroimmunization of pregnant guinea-pigs may be transmitted to offspring in the last third of the gestation period and can bind to fetal TBM. However, this transfer of antibodies does not cause disease.

  8. In vivo turnover of the basement membrane and other heparan sulfate proteoglycans of rat glomerulus

    Energy Technology Data Exchange (ETDEWEB)

    Beavan, L.A.; Davies, M.; Couchman, J.R.; Williams, M.A.; Mason, R.M.


    The metabolic turnover of rat glomerular proteoglycans in vivo was investigated. Newly synthesized proteoglycans were labeled during a 7-h period after injecting sodium (35S)sulfate intraperitoneally. At the end of the labeling period a chase dose of sodium sulfate was given. Subsequently at defined times (0-163 h) the kidneys were perfused in situ with 0.01% cetylpyridinium chloride in phosphate-buffered saline to maximize the recovery of 35S-proteoglycans. Glomeruli were isolated from the renal cortex and analyzed for 35S-proteoglycans by autoradiographic, biochemical, and immunochemical methods. Grain counting of autoradiographs revealed a complex turnover pattern of 35S-labeled macromolecules, commencing with a rapid phase followed by a slower phase. Biochemical analysis confirmed the biphasic pattern and showed that the total population of (35S)heparan sulfate proteoglycans had a metabolic half-life (t1/2) of 20 and 60 h in the early and late phases, respectively. Heparan sulfate proteoglycans accounted for 80% of total 35S-proteoglycans, the remainder being chondroitin/dermatan sulfate proteoglycans. Whole glomeruli were extracted with 4% 3-((cholamidopropyl)dimethy-lammonio)-1-propanesulfonate-4 M guanidine hydrochloride, a procedure which solubilized greater than 95% of the 35S-labeled macromolecules. Of these 11-13% was immunoprecipitated by an antiserum against heparan sulfate proteoglycan which, in immunolocalization experiments, showed specificity for staining the basement membrane of rat glomeruli. Autoradiographic analysis showed that 18% of total radioactivity present at the end of the labeling period was associated with the glomerular basement membrane.

  9. Basement membrane reconstruction in human skin equivalents is regulated by fibroblasts and/or exogenously activated keratinocytes

    NARCIS (Netherlands)

    El Ghalbzouri, A; Jonkman, MF; Dijkman, R; Ponec, M


    This study was undertaken to examine the role fibroblasts play in the formation of the basement membrane (BM) in human skin equivalents. For this purpose, keratinocytes were seeded on top of fibroblast-free or fibroblast-populated collagen matrix or de-epidermized dermis and cultured in the absence

  10. Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall. (United States)

    de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues


    The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

  11. Basement Membrane Zone Collagens XV and XVIII/Proteoglycans Mediate Leukocyte Influx in Renal Ischemia/Reperfusion

    NARCIS (Netherlands)

    Zaferani, Azadeh; Talsma, Ditmer T.; Yazdani, Saleh; Celie, Johanna W. A. M.; Aikio, Mari; Heljasvaara, Ritva; Navis, Gerjan J.; Pihlajaniemi, Taina; van den Born, Jacob


    Collagen type XV and XVIII are proteoglycans found in the basement membrane zones of endothelial and epithelial cells, and known for their cryptic anti-angiogenic domains named restin and endostatin, respectively. Mutations or deletions of these collagens are associated with eye, muscle and microves

  12. Insecticidal Activity of a Basement Membrane-Degrading Protease against Heliothis virescens (Fabricius) and Acyrthosiphon pisum (Harris) (United States)

    ScathL is a cathepsin L-like cysteine protease derived from the flesh fly Sarcophaga peregrina that functions in basement membrane (BM) remodeling during insect development. A recombinant baculovirus expressing ScathL (AcMLF9.ScathL) kills larvae of the tobacco budworm, Heliothis virescens, signific...

  13. MT1-MMP-mediated basement membrane remodeling modulates renal development

    Energy Technology Data Exchange (ETDEWEB)

    Riggins, Karen S.; Mernaugh, Glenda [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Su, Yan; Quaranta, Vito [Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Koshikawa, Naohiko; Seiki, Motoharu [Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Pozzi, Ambra [Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Research Medicine, Veterans Affairs Hospital, Nashville, TN 37232 (United States); Zent, Roy, E-mail: [Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Research Medicine, Veterans Affairs Hospital, Nashville, TN 37232 (United States)


    Extracellular matrix (ECM) remodeling regulates multiple cellular functions required for normal development and tissue repair. Matrix metalloproteinases (MMPs) are key mediators of this process and membrane targeted MMPs (MT-MMPs) in particular have been shown to be important in normal development of specific organs. In this study we investigated the role of MT1-MMP in kidney development. We demonstrate that loss of MT1-MMP leads to a renal phenotype characterized by a moderate decrease in ureteric bud branching morphogenesis and a severe proliferation defect. The kidneys of MT1-MMP-null mice have increased deposition of collagen IV, laminins, perlecan, and nidogen and the phenotype is independent of the MT-1MMP target, MMP-2. Utilizing in vitro systems we demonstrated that MTI-MMP proteolytic activity is required for renal tubule cells to proliferate in three dimensional matrices and to migrate on collagen IV and laminins. Together these data suggest an important role for MT1-MMP in kidney development, which is mediated by its ability to regulate cell proliferation and migration by proteolytically cleaving kidney basement membrane components.

  14. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane

    Energy Technology Data Exchange (ETDEWEB)



    An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and sequester milk proteins. Previous culture studies have described either organization of cells polarized towards lumina containing little or no demonstrable tissue-specific protein, or establishment of functional secretory cells exhibiting little or no glandular architecture. In this paper, we report that tissue-specific vectorial secretion coincides with the formation of functional alveoli-like structures by primary mammary epithelial cells cultured on a reconstituted basement membrane matrix (derived from Engelbreth-Holm-Swarm murine tumour). Morphogenesis of these unique three-dimensional structures was initiated by cell-directed remodelling of the exogenous matrix leading to reorganization of cells into matrixensheathed aggregates by 24 h after plating. The aggregates subsequently cavitated, so that by day 6 the cells were organized into hollow spheres in which apical cell surfaces faced lumina sealed by tight junctions and basal surfaces were surrounded by a distinct basal lamina. The profiles of proteins secreted into the apical (luminal) and basal (medium) compartments indicated that these alveoli-like structures were capable of an appreciable amount of vectorial secretion. Immunoprecipitation with a broad spectrum milk antiserum showed that more than 80% of caseins were secreted into the lumina, whereas iron-binding proteins (both lactoferrin and transferrin) were present in comparable amounts in each compartment. Thus, these mammary cells established protein targeting pathways directing milk-specific proteins to the luminal compartment. A time course monitoring secretory activity demonstrated that establishment of tissue-specific vectorial secretion and increased total and milk protein secretion coincided with functional alveolar

  15. Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease

    Directory of Open Access Journals (Sweden)

    Cristen Chafin


    Full Text Available Cristen Chafin2, Sarah Muse2, Raquel Hontecillas5, Josep Bassaganya-Riera5, David L Caudell2, Samuel K Shimp III4, M Nichole Rylander4, John Zhang6, Liwu Li3, Christopher M Reilly1,21Virginia College of Osteopathic Medicine, 2Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 3Department of Biological Sciences, 4Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 5Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 6Medical University of SC, Charleston, SC, USAAbstract: Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR-γ has been shown to be immunoregulatory in autoimmune diseases by inhibiting production of a number of inflammatory mediators. We investigated whether PPAR-γ gene deletion in hematopoietic cells would alter disease pathogenesis in the antiglomerular basement membrane (anti-GBM mouse model. PPAR-γ+/+ and PPAR-γ-/- mice were immunized with rabbit antimouse GBM antibodies and lipopolysaccharide and evaluated for two weeks. Although both the PPAR-γ+/+ and PPAR-γ-/- mice had IgG deposition in the glomerulus and showed proteinuria two weeks after injection, glomerular and tubulointerstitial disease in PPAR-γ-/- mice were significantly more severe compared with the PPAR-γ+/+ animals. We observed that the PPAR-γ-/- mice had decreased CD4+CD25+ regulatory T cells and an increased CD8+:CD4+ ratio as compared with the PPAR-γ+/+ mice, suggesting that PPAR-γ has a role in the regulation of T cells. Furthermore, plasma interleukin-6 levels were significantly increased in the PPAR-γ-/- mice at two weeks as compared with the PPAR-γ+/+ animals. Taken together, these studies show that

  16. Does Tensile Rupture of Tumor Basement Membrane Mark the Onset of Cancer Metastasis? (United States)

    Prakash, Sai


    Recognizing a conceptual analogy from polymer physics and reasoning via induction, we infer the plausibility that a malignant tumor (carcinoma) grows in size until a threshold determined by its mechanochemical state in relation to its microenvironment whence, peripheral cells undergo epithelial-to-mesenchymal transitions (EMT) facilitating metastasis. This state is equated to the tensile yielding/rupture of the proteolytically-weakened basement membrane (BM) that encapsulates the growing neoplasm. BMs are typically constituted of tri-continuous hydrogel networks of collagen-IV, laminin, and interstitial fluid, with connector proteins such as nidogens, and perlecans. We test this postulate by formulating a theoretical model based on continuum fluid-solid mechanics, diffusion, and biochemical kinetics of energy metabolism. Herein, a prototypical, viscous tumor spheroid grows radially, consuming metabolic nutrients while being constrained by an elastic BM ca. 0.5-2 microns-thick, and cell adhesion molecules (CAMs), chiefly cadherins and integrins. The model is computationally analyzed via Comsol®. Results validate the a priori conjecture, and predict subsequent crack-tip stresses shifting strains on the CAMs from compressive to tensile, that might also indicate mechanotransduced switches in their conformations, such as from non-invasive, adhesive E-cadherins to invasive, non-adhesive N-cadherin phenotypes. Grant from Brady Urological Institute, JHMI.

  17. Integrating Activities of Laminins that Drive Basement Membrane Assembly and Function. (United States)

    Yurchenco, Peter D


    Studies on extracellular matrix proteins, cells, and genetically modified animals have converged to reveal mechanisms of basement membrane self-assembly as mediated by γ1 subunit-containing laminins, the focus of this chapter. The basic model is as follows: A member of the laminin family adheres to a competent cell surface and typically polymerizes followed by laminin binding to the extracellular adaptor proteins nidogen, perlecan, and agrin. Assembly is completed by the linking of nidogen and heparan sulfates to type IV collagen, allowing it to form a second stabilizing network polymer. The assembled matrix provides structural support, anchoring the extracellular matrix to the cytoskeleton, and acts as a signaling platform. Heterogeneity of function is created in part by the isoforms of laminin that vary in their ability to polymerize and to interact with integrins, dystroglycan, and other receptors. Mutations in laminin subunits, affecting expression or LN domain-specific functions, are a cause of human diseases that include those of muscle, nerve, brain, and kidney.

  18. Numerical analysis of viscous flow through fibrous media: a model for glomerular basement membrane permeability. (United States)

    Palassini, M; Remuzzi, A


    Viscous flow through fibrous media is characterized macroscopically by the Darcy permeability (KD). The relationship between KD and the microscopic structure of the medium has been the subject of experimental and theoretical investigations. Calculations of KD based on the solution of the hydrodynamic flow at fiber scale exist in literature only for two-dimensional arrays of parallel fibers. We considered a fiber matrix consisting of a three-dimensional periodic array of cylindrical fibers with uniform radius (r) and length connected in a tetrahedral structure. According to recent ultrastructural studies, this array of fibers can represent a model for the glomerular basement membrane (GBM). The Stokes flow through the periodic array was simulated using a Galerkin finite element method. The dimensionless ratio K* = KD/r2 was determined for values of the fractional solid volume (phi) in the range 0.005 equation only for phi > 0.4. Among the other theoretical analysis considered, only that of Spielman and Goren (Environ. Sci. Technol. 2: 279-287, 1968) gives satisfactory agreement in the whole range of phi considered. These results can be useful to model combined transport of water and macromolecules through the GBM for the estimation of the radius and length of extracellular protein fibrils.

  19. Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of the oral mucosa. (United States)

    Arduino, Paolo G; Carrozzo, Marco; Pagano, Marco; Broccoletti, Roberto; Scully, Crispian; Gandolfo, Sergio


    Squamous cell carcinoma (SCC) of the oral cavity is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extra-cellular matrix. Oral verrucous carcinoma (VC) is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. It also has a different clinical behaviour from classical oral SCC. We investigated the immunohistochemical expression of laminin, laminin-5, collagen IV and fibronectin in VC, severe epithelial dysplasia (SED) and SCC in order to analyse if the pattern of these molecules expression contributes to the differences in the biological behaviour of these diseases. The staining pattern of laminin was less intensive in SCC compared with SED and VC, and collagen IV expression was increased in VC compared with SED. Discontinuities of laminin, collagen IV and fibronectin were more evident in SED than in VC. This study indicates that VC has a biological behaviour different from SED or SCC, observable by immunohistochemistry in the BM zone.

  20. Vascular Basement Membrane-derived Multifunctional Peptide, a Novel Inhibitor of Angiogenesis and Tumor Growth

    Institute of Scientific and Technical Information of China (English)

    Jian-Guo CAO; Shu-Ping PENG; Li SUN; Hui LI; Li WANG; Han-Wu DENG


    Vascular basement membrane-derived multifunctional peptide (VBMDMP) gene (fusion gene of the human immunoglobulin G3 upper hinge region and two tumstatin-derived fragments) obtained by chemical synthesis was cloned into vector pUC 19, and introduced into the expression vector pGEX-4T-1 to construct a prokaryotic expression vector pGEX-4T-1-VBMDMP. Recombinant VBMDMP produced in Escherichia coli has been shown to have significant activity of antitumor growth and antimetastasis in Lewis lung carcinoma transplanted into mouse C57B1/6. In the present study, we have studied the ability of rVBMDMP to inhibit endothelial cell tube formation and proliferation, to induce apoptosis in vitro, and to suppress tumor growth in vivo. The experimental results showed that rVBMDMP potently inhibited proliferation of human endothelial (HUVEC-12) cells and human colon cancer (SW480) cells in vitro, with no inhibition of proliferation in Chinese hamster ovary (CHO-K1) cells. rVBMDMP also significantly inhibited human endothelial cell tube formation and suppressed tumor growth of SW480 cells in a mouse xenograft model. These results suggest that rVBMDMP is a powerful therapeutic agent for suppressing angiogenesis and tumor growth.

  1. Role of the basement membrane in regulation of cardiac electrical properties. (United States)

    Yang, Huaxiao; Borg, Thomas K; Wang, Zhonghai; Ma, Zhen; Gao, Bruce Z


    In the heart muscle, each adult cardiomyocyte is enclosed by a basement membrane (BM). This innermost extracellular matrix is a layered assembly of laminin, collagen IV, glycoproteins, and proteoglycans. In this study, the role of the BM network in regulation of the electrical properties of neonatal cardiomyocytes (NCMs) cultured on an aligned collagen I gel was investigated using a multielectrode array (MEA). A laminin antibody was added to the culture medium for 48-120 h to conjugate newly secreted laminin. Then, morphology of the NCMs on an MEA was monitored using a phase contrast microscope, and the BM network that was immunocytostained for laminin was imaged using a fluorescence microscope. When the BM laminin was absent in this culture model, dramatic changes in NCM morphology were observed. Simultaneously, the MEA-recorded cardiac field potential showed changes compared to that from the control groups: The period of contraction shortened to 1/2 of that from the control groups, and the waveform of the calcium influx shifted from a flat plateau to a peak-like waveform, indicating that the electrical properties of the NCMs were closely related to the components and distribution of the BM network.

  2. Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma. (United States)

    Kim, Nan-Hyung; Choi, Soo-Hyun; Lee, Tae Ryong; Lee, Chang-Hoon; Lee, Ai-Young


    Basement membrane (BM) disruption and dermal changes (elastosis, collagenolysis, vascular ectasia) have been reported in melasma. Although ultraviolet (UV) irradiation can induce these changes, UV is not always necessary for melasma development. Cadherin 11 (CDH11), which is upregulated in some melasma patients, has previously been shown to stimulate melanogenesis. Because CDH11 action requires cell-cell adhesion between fibroblasts and melanocytes, BM disruption in vivo should facilitate this. The aim of this study was to examine whether CDH11 overexpression leads to BM disruption and dermal changes, independent of UV irradiation. Immunohistochemistry/immunofluorescence, real-time PCR, Western blotting, and zymography suggested that BM disruption/dermal changes and related factors were present in the hyperpigmented skin of CDH11-upregulated melasma patients and in CDH11-overexpressing fibroblasts/keratinocytes. The opposite was seen in CDH11-knockdown cells. UV irradiation of the cultured cells did not increase CDH11 expression. Collectively, these data demonstrate that CDH11 overexpression could induce BM disruption and dermal changes in melasma, regardless of UV exposure.

  3. Chitosan facilitates structure formation of the salivary gland by regulating the basement membrane components. (United States)

    Yang, Tsung-Lin; Hsiao, Ya-Chuan


    Tissue structure is important for inherent physiological function and should be recapitulated during tissue engineering for regenerative purposes. The salivary gland is a branched organ that is responsible for saliva secretion and regulation. The salivary glands develop from epithelial-mesenchymal interactions, and depend on the support of the basement membrane (BM). Chitosan-based biomaterials have been demonstrated to be competent in facilitating the formation of salivary gland tissue structure. However, the underlying mechanisms have remained elusive. In the developing submandibular gland (SMG), the chitosan effect was found to diminish when collagen and laminin were removed from cultured SMG explants. Chitosan increased the expression of BM components including collagen, laminin, and heparan sulfate proteoglycan, and also facilitated BM components and the corresponding receptors to be expressed in tissue-specific patterns beneficial for SMG branching. The chitosan effect decreased when either laminin components or receptors were inhibited, as well when the downstream signaling was blocked. Our results revealed that chitosan promotes salivary glands branching through the BM. By regulating BM components and receptors, chitosan efficiently stimulated downstream signaling to facilitate salivary gland branching. The present study revealed the underlying mechanism of the chitosan effect in engineering SMG structure formation.

  4. Anti-glomerular basement membrane glomerulonephritis in an HIV positive patient: case report

    Directory of Open Access Journals (Sweden)

    Eduardo José Bellotto Monteiro


    Full Text Available We report on a case of a patient with HIV infection, diagnosed 18 months prior to the development of an anti-glomerular basement membrane (anti-GBM rapidly progressive glomerulonephritis; this is probably the first report of such an association. A 30-year-old white man presented with elevation of serum creatinine (1.3 - 13.5 mg/dL within one month. At admission, the urinalysis showed proteinuria of 7.2 g/L and 8,000,000 erythrocytes/mL. Renal biopsy corresponded to a crescentic diffuse proliferative glomerulonephritis mediated by anti-GBM, and serum testing for anti-GBM antibodies was positive; antinuclear antibodies (ANA and anti-neutrophilic cytoplasmic antibodies (ANCA were also positive. The patient underwent hemodyalisis and was treated with plasmapheresis, cyclophosphamide and prednisone. The association described here is not casual, as crescentic glomerulonephritis is not common in HIV-positive patients, anti-GBM glomerulonephritis is rare and anti-GBM antibodies are frequently observed in HIV-positive subjects when compared to the overall population. Based on the current case and on the elevated frequency of the positivity for such antibodies in this group of patients, it is advisable to be aware of the eventual association between these two conditions and to promote an active search for anti-GBM antibodies and early diagnosis of eventual urinary abnormalities in HIV-positive subjects, considering the severity of anti-GBM glomerulonephritis.

  5. De novo deposition of laminin-positive basement membrane in vitro by normal hepatocytes and during hepatocarcinogenesis

    DEFF Research Database (Denmark)

    Albrechtsen, R; Wewer, U M; Thorgeirsson, S S


    De novo formation of laminin-positive basement membranes was found to be a distinct morphologic feature of diethylnitrosamine/phenobarbital-induced hepatocellular carcinomas of the rat. The first appearance of extracellularly located laminin occurred in the preneoplastic liver lesions...... (corresponding to neoplastic nodules), and this feature became successively more prominent during the course of hepatocellular carcinoma development. Most groups of tumor cells were surrounded by laminin-positive basement membrane material. The laminin-positive material was also deposited along the sinusoids......, a location where no laminin was seen in normal rat liver. The amount of extractable laminin from hepatocellular carcinomas was significantly higher (approximately 100 ng per mg tissue) than that of normal liver tissue (less than 20 ng per mg). In vitro experiments demonstrated that normal and preneoplastic...

  6. Distribution of two basement membrane proteoglycans through hair follicle development and the hair growth cycle in the rat

    DEFF Research Database (Denmark)

    Couchman, J R; King, J L; McCarthy, K J


    The distribution of two distinct populations of basement membrane proteoglycans has been monitored through hair growth development in the rat embryo and subsequent hair growth cycle. An antiserum against a small heparan sulfate proteoglycan uniformly stained the dermal-epidermal junction...... of embryonic rats throughout the period of hair follicle formation. On the other hand, monoclonal antibodies recognizing a basement membrane-specific chondroitin sulfate proteoglycan only weakly stained 16-d embryo dermal-epidermal junction, but strong staining was associated with hair follicle buds...... as they developed. Through the hair growth cycle, it was found that the heparan sulfate proteoglycan persisted around the follicles, while the chondroitin sulfate proteoglycan decreased in amount through catagen until it was undetectable at the base and dermal papilla of the telogen follicle. As anagen commenced...

  7. Ultrastructural localization of the core protein of a basement membrane-specific chondroitin sulfate proteoglycan in adult rat skin

    DEFF Research Database (Denmark)

    McCarthy, K J; Horiguchi, Y; Couchman, J R


    Basement membranes are complex extracellular matrices present at epithelial/mesenchymal interfaces of tissues. The dermal-epidermal junction has been shown to contain numerous components, some of the most well known being laminin, types IV and VII collagens, heparan sulfate proteoglycan, fibronec......Basement membranes are complex extracellular matrices present at epithelial/mesenchymal interfaces of tissues. The dermal-epidermal junction has been shown to contain numerous components, some of the most well known being laminin, types IV and VII collagens, heparan sulfate proteoglycan...... primarily within the basal lamina, apparently concentrated in the lamina densa. In addition, some of the proteoglycan was also present beneath the lamina densa, associated with the reticular lamina collagen fibrils....

  8. Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse

    DEFF Research Database (Denmark)

    Xu, H; Christmas, P; Wu, X R;


    M-laminin is a major member of the laminin family of basement membrane proteins. It is prominently expressed in striated muscle and peripheral nerve. M-laminin is deficient in patients with the autosomal recessive Fukuyama congenital muscular dystrophy but is normal in patients with the sex......-linked Duchenne and Becker muscular dystrophies. We have examined M-laminin expression in mice with autosomal recessive muscular dystrophy caused by the mutation dy. The heavy chain of M-laminin was undetectable in skeletal muscle, heart muscle, and peripheral nerve by immunofluorescence and immunoblotting...... in homozygous dystrophic dy/dy mice but was normal in heterozygous and wild-type nondystrophic mice. Immunofluorescence confirmed the presence of other major basement membrane proteins in the dystrophic mice. Very low levels of M-laminin heavy chain mRNA were detected by Northern blotting of muscle and heart...

  9. Scaffold-forming and Adhesive Contributions of Synthetic Laminin-binding Proteins to Basement Membrane Assembly*S⃞


    McKee, Karen K.; Capizzi, Stephanie; Yurchenco, Peter D.


    Laminins that possess three short arms contribute to basement membrane assembly by anchoring to cell surfaces, polymerizing, and binding to nidogen and collagen IV. Although laminins containing the α4 and α5 subunits are expressed in α2-deficient congenital muscular dystrophy, they may be ineffective substitutes because they bind weakly to cell surfaces and/or because they lack the third arm needed for polymerization. We asked whether linker proteins engineered to bind...

  10. Lysyl Hydroxylase 3 Localizes to Epidermal Basement Membrane and Is Reduced in Patients with Recessive Dystrophic Epidermolysis Bullosa.

    Directory of Open Access Journals (Sweden)

    Stephen A Watt

    Full Text Available Recessive dystrophic epidermolysis bullosa (RDEB is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3, in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention.

  11. IgE basement membrane zone antibodies induce eosinophil infiltration and histological blisters in engrafted human skin on SCID mice. (United States)

    Zone, John J; Taylor, Ted; Hull, Christopher; Schmidt, Linda; Meyer, Laurence


    Bullous pemphigoid (BP) is characterized by the deposition of IgG in the basement membrane zone, infiltration of eosinophils, and blister formation. The purpose of this study was to evaluate a potential role of IgE basement membrane antibodies in the histological findings of BP. LABD97 is a component of the shed ectodomain of bullous pemphigoid antigen 2. We have developed an IgE hybridoma to LABD97 antigen. This hybridoma was injected subcutaneously in SCID mice with engrafted human skin. A subcutaneous hybridoma secreting IgE antibodies developed. An IgE mouse hybridoma to trinitrophenyl was used as a control. Human grafts and mouse skin were examined grossly over 21 days, histologically, and immunopathologically at day 21 after injection of the hybridoma. A visible subcutaneous tumor developed in 10-14 days. Erythema and intense scratching developed 2-3 days before the tumor in test mice, but not in controls. At day 21, 16/16 test mice developed intense eosinophil infiltration and degranulation of the human mast cells within the grafts and 13/16 developed histological, but not clinically visible, basement membrane blisters. Human skin grafts of control mice and normal mouse skin on the test mice and control mice did not develop any histological abnormalities. IgE antibodies to LABD97 recapitulate the histological inflammatory process seen in BP.

  12. A Case of Fibrillary Glomerulonephritis Associated with Thrombotic Microangiopathy and Anti-Glomerular Basement Membrane Antibody

    Directory of Open Access Journals (Sweden)

    Akishi Momose


    Full Text Available We present the first report of a case of fibrillary glomerulonephritis (FGN associated with thrombotic microangiopathy (TMA and anti-glomerular basement membrane antibody (anti-GBM antibody. A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction. Laboratory data revealed normocytic-normochromic anemia with schistocytes in the peripheral smear, thrombocytopenia, increased serum lactate dehydrogenase, decreased serum haptoglobin, and negative results for both direct and indirect Coombs tests. Based on these results, we diagnosed TMA. Assays conducted several days later indicated a disintegrin-like and metalloprotease with a thrombospondin motif 13 (ADAMTS13 activity of 31.6%, and ADAMTS13 inhibitors were negative. We started plasma exchange using fresh frozen plasma and steroid pulse therapy. Anti-GBM antibody was found to be positive. Renal biopsy showed FGN. Blood pressure rose on the 46th hospital day, and mild convulsions developed. Based on magnetic resonance imaging of the head, the patient was diagnosed with reversible posterior leukoencephalopathy syndrome. Hypertension persisted despite administration of multiple antihypertensive agents, and the patient experienced a sudden generalized seizure. Computed tomography of the head showed multiple cerebral hemorrhages. However, his blood pressure subsequently decreased and the platelet count increased. TMA remitted following 36 plasma exchange sessions, but renal function was not restored, and maintenance hemodialysis was continued. The patient was discharged on the 119th day of hospitalization. In conclusion, it was shown that TMA, FGN and anti-GBM antibody were closely related.

  13. Putative role of basement membrane for dentinogenesis in the mesenchyme of murine dental papillae in vitro. (United States)

    Kikuchi, H; Amano, H; Yamada, S


    In a new culture-conditioning system of agar-coated mesenchyme of isolated incisor dental papillae, dentinogenesis has been induced adjacent to an agar substratum that functions as a foothold for cell immobilisation. To elucidate the role of the basement membrane (BM) in dentinogenesis, we have examined the way in which dentinogenesis depends upon BM components or transforming growth factor (TGF)-beta1 in this system. At the mesenchymal-epithelial junction of odontogenic organs (cut incisor tooth germs), TGF-beta1 visibly increased in the BM during incubation. In isolated dental papillae, BM components were synthesised and deposited at aligned peripheral cells of the explants, together with an increasing amount of TGF-beta1. These components were not assembled into extracellular matrix (ECM)-absorbed agar adjacent to explants, although dentinogenesis proceeded in the presence of pericellular BM components associated with TGF-beta1. When signalling via TGF-beta type II receptors was blocked, neither ECM production nor dentinogenesis was observed but explants partially detached from the agar surface, presumably as a result of the suppressed production of ECM, since attachment was retained by pre-coating explants with artificial matrices. Rescue experiments showed that TGF-beta1 regulated dentinogenesis through ECM production. With regard to BM components, inducible dentinogenesis was Arg-Gly-Asp (RGD)-dependent. Thus, pericellular BM components associated with TGF-beta1 and an ECM-absorbed agar substratum, which affects dentinogenesis, synergistically play a role similar to that of BM components in vivo. The BM therefore serves as a structural meshwork that acts as a foothold for cell immobilisation; its components act as ligands for RGD-dependent cell adhesion and it stores TGF-beta1, which regulates ECM production.

  14. Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules (United States)

    Lawrence, Marlon G.; Altenburg, Michael K.; Sanford, Ryan; Willett, Julian D.; Bleasdale, Benjamin; Ballou, Byron; Wilder, Jennifer; Li, Feng; Miner, Jeffrey H.; Berg, Ulla B.; Smithies, Oliver


    How the kidney prevents urinary excretion of plasma proteins continues to be debated. Here, using unfixed whole-mount mouse kidneys, we show that fluorescent-tagged proteins and neutral dextrans permeate into the glomerular basement membrane (GBM), in general agreement with Ogston's 1958 equation describing how permeation into gels is related to molecular size. Electron-microscopic analyses of kidneys fixed seconds to hours after injecting gold-tagged albumin, negatively charged gold nanoparticles, and stable oligoclusters of gold nanoparticles show that permeation into the lamina densa of the GBM is size-sensitive. Nanoparticles comparable in size with IgG dimers do not permeate into it. IgG monomer-sized particles permeate to some extent. Albumin-sized particles permeate extensively into the lamina densa. Particles traversing the lamina densa tend to accumulate upstream of the podocyte glycocalyx that spans the slit, but none are observed upstream of the slit diaphragm. At low concentrations, ovalbumin-sized nanoparticles reach the primary filtrate, are captured by proximal tubule cells, and are endocytosed. At higher concentrations, tubular capture is saturated, and they reach the urine. In mouse models of Pierson’s or Alport’s proteinuric syndromes resulting from defects in GBM structural proteins (laminin β2 or collagen α3 IV), the GBM is irregularly swollen, the lamina densa is absent, and permeation is increased. Our observations indicate that size-dependent permeation into the lamina densa of the GBM and the podocyte glycocalyx, together with saturable tubular capture, determines which macromolecules reach the urine without the need to invoke direct size selection by the slit diaphragm. PMID:28246329

  15. Long-term outcome of anti-glomerular basement membrane antibody disease treated with immunoadsorption.

    Directory of Open Access Journals (Sweden)

    Peter Biesenbach

    Full Text Available Anti-glomerular basement membrane (GBM antibody disease may lead to acute crescentic glomerulonephritis with poor renal prognosis. Current therapy favours plasma exchange (PE for removal of pathogenic antibodies. Immunoadsorption (IAS is superior to PE regarding efficiency of antibody-removal and safety. Apart from anecdotal data, there is no systemic analysis of the long-term effects of IAS on anti-GBM-disease and antibody kinetics.To examine the long-term effect of high-frequency IAS combined with standard immunosuppression on patient and renal survival in patients with anti-GBM-disease and to quantify antibody removal and kinetics through IAS.Retrospective review of patients treated with IAS for anti-GBM-antibody disease confirmed by biopsy and/or anti-GBM-antibodies.University Hospital of Vienna, Austria.10 patients with anti-GBM-disease treated with IAS.Patient and renal survival, renal histology, anti-GBM-antibodies.Anti-GBM-antibodies were reduced by the first 9 IAS treatments (mean number of 23 to negative levels in all patients. Renal survival was 40% at diagnosis, 70% after the end of IAS, 63% after one year and 50% at the end of observation (mean 84 months, range 9 to 186. Dialysis dependency was successfully reversed in three of six patients. Patient survival was 90% at the end of observation.IAS efficiently eliminates anti-GBM-antibodies suggesting non-inferiority to PE with regard to renal and patient survival. Hence IAS should be considered as a valuable treatment option for anti-GBM-disease, especially in patients presenting with a high percentage of crescents and dialysis dependency due to an unusual high proportion of responders.

  16. The deformation matrix theory of basement membrane: a study of water flow through elastic and rigid filaments in the rat. (United States)

    Fisher, R F


    1. When the volume of water per unit time which flows through natural elastic basement membrane is divided by the applied pressure, the value-the hydraulic conductivity-is not constant but decreases as pressure increases. In contrast when the same membrane is tanned with glutaraldehyde and rendered inelastic, the hydraulic conductivity is constant at all pressures. 2. Over a pressure range of 0-6.7 kPa equivalent to a membrane stress of 0-195 kPa in natural elastic membrane the hydraulic conductivity (Lp) can be related by the linear equation Lp = Lp.0 + apP where P is the hydraulic pressure, Lp.0 is the initial hydraulic conductivity and ap is a constant which is the decreased hydraulic conductivity per unit pressure (correlation coefficient 0.764. P less than 0.001). 3. The initial conductivity of the basement membrane of the crystalline lens of the adult rat (lens capsule) was 47.6 +/- 7.3 x 10(-12) m s-1 Pa-1 while the decrease in hydraulic conductivity per unit increase in pressure was -3.38 x 10(-15) m s-1 Pa-2. 4. Following tanning with glutaraldehyde the hydraulic conductivity was constant at 27.4 +/- 4.0 x 10(-12) m s-1 Pa-1. 5. A change in the configuration of the superhelices of the filaments of type IV collagen which form the framework of basement membrane is termed. 'The deformation matrix theory' and can satisfactorily account for the changes in hydraulic conductivity of both natural and tanned membrane. 6. In natural membrane the filaments deform easily and the pitch of the filament superhelices is increased by axial stress induced by pressure. The filaments straighten and become compacted together and the hydraulic permeability is thereby decreased. 7. In tanned membrane the filaments become more rigid and axial stress barely deforms them: moreover the pitch of the filament superhelices is decreased so that the filaments become more closely coiled and compacted together. Because of these changes the hydraulic conductivity is reduced as compared with

  17. Laminin and Type IV Collagen Isoform Substitutions Occur in Temporally and Spatially Distinct Patterns in Developing Kidney Glomerular Basement Membranes


    Abrahamson, Dale R.; St. John, Patricia L.; Stroganova, Larysa; Zelenchuk, Adrian; Steenhard, Brooke M.


    Kidney glomerular basement membranes (GBMs) undergo laminin and type IV collagen isoform substitutions during glomerular development, which are believed to be required for maturation of the filtration barrier. Specifically, GBMs of earliest glomeruli contain laminin α1β1γ1 and collagen α1α2α1(IV), whereas mature glomeruli contain laminin α5β2γ1 and collagen α3α4α5(IV). Here, we used confocal microscopy to simultaneously evaluate expression of different laminin and collagen IV isoforms in newb...

  18. Basement membrane and interstitial proteoglycans produced by MDCK cells correspond to those expressed in the kidney cortex

    DEFF Research Database (Denmark)

    Erickson, A C; Couchman, J R


    ) cells has been utilized. Proteoglycans were prepared from conditioned medium by DEAE anion exchange chromatography. The eluted PGs were treated with heparitinase or chondroitinase ABC (cABC), separately or combined, followed by SDS-PAGE. Western blot analysis, using antibodies specific for various PG...... core proteins or CS stubs generated by cABC treatment, revealed that both basement membrane and interstitial PGs are secreted by MDCK cells. HSPGs expressed by MDCK cells are perlecan, agrin, and collagen XVIII. Various CSPG core proteins are made by MDCK cells and have been identified as biglycan...

  19. A model of strain-dependent glomerular basement membrane maintenance and its potential ramifications in health and disease. (United States)

    Barocas, Victor H; Dorfman, Kevin D; Segal, Yoav


    A model is developed and analyzed for type IV collagen turnover in the kidney glomerular basement membrane (GBM), which is the primary structural element in the glomerular capillary wall. The model incorporates strain dependence in both deposition and removal of the GBM, leading to an equilibrium tissue strain at which deposition and removal are balanced. The GBM thickening decreases tissue strain per unit of transcapillary pressure drop according to the law of Laplace, but increases the transcapillary pressure drop required to maintain glomerular filtration. The model results are in agreement with the observed GBM alterations in Alport syndrome and thin basement membrane disease, and the model-predicted linear relation between the inverse capillary radius and inverse capillary thickness at equilibrium is consistent with published data on different mammals. In addition, the model predicts a minimum achievable strain in the GBM based on the geometry, properties, and mechanical environment; that is, an infinitely thick GBM would still experience a finite strain. Although the model assumptions would be invalid for an extremely thick GBM, the minimum achievable strain could be significant in diseases, such as Alport syndrome, characterized by focal GBM thickening. Finally, an examination of reasonable values for the model parameters suggests that the oncotic pressure drop-the osmotic pressure difference between the plasma and the filtrate due to large molecules-plays an important role in setting the GBM strain and, thus, leakage of protein into the urine may be protective against some GBM damage.

  20. [Ultrastructure of glomerular podocyts in the incipient phase of minimal change nephrotic syndrome with thin basement membrane disease]. (United States)

    Ogawa, Ryo; Miyoshi, Ken-ichi; Nagao, Tomoaki; Jotoku, Masanori; Irita, Jun; Okura, Takafumi; Higaki, Jitsuo


    An 80-year-old woman was referred to the Division of Nephrology at Ehime University Hospital because of leg edema in December 2010. She had been treated with 300 mg of tocopherol for scleroderma since 2007 and treated with 9 mg of prednisolone (PSL) for autoimmune hearing loss since 2010. Due to the occurrence of mild hematuria (5-9/HPF), proteinuria (0.9 g/day) and an increased serum creatinine level (1.31 mg/dL), a renal biopsy was performed. Light microscopy (LM) showed minor abnormality in the glomeruli, and immunohistology showed the absence of deposits of immunoglobulins and complements. Electron microscopy (EM) showed a thin glomerular basement membrane with a limited level of podocyte abnormalities. Due to the findings of intimal thickening of interlobular arteries and subcapsular accumulation of global sclerosis on LM, she was diagnosed with nephrosclerosis and thin basement membrane disease. Four weeks later, her leg edema had increased considerably and urinary protein had increased to 12.4 g/day. The second biopsy showed similar findings in LM and IF as the first biopsy, but EM revealed diffuse foot process effacement. She was diagnosed with minimal change nephrotic syndrome (MCNS) and treated with methylprednisolone pulse therapy followed by 40 mg of oral PSL. Her urinary protein had completely disappeared 6 weeks later. Complete remission with PSL treatment indicates that urinary protein at first renal biopsy was due to MCNS. Our case exhibited podocyte features in the incipient phase of human MCNS.

  1. cDNA cloning of the basement membrane chondroitin sulfate proteoglycan core protein, bamacan: a five domain structure including coiled-coil motifs

    DEFF Research Database (Denmark)

    Wu, R R; Couchman, J R


    Basement membranes contain several proteoglycans, and those bearing heparan sulfate glycosaminoglycans such as perlecan and agrin usually predominate. Most mammalian basement membranes also contain chondroitin sulfate, and a core protein, bamacan, has been partially characterized. We have now...... obtained cDNA clones encoding the entire bamacan core protein of Mr = 138 kD, which reveal a five domain, head-rod-tail configuration. The head and tail are potentially globular, while the central large rod probably forms coiled-coil structures, with one large central and several very short interruptions....... This molecular architecture is novel for an extracellular matrix molecule, but it resembles that of a group of intracellular proteins, including some proposed to stabilize the mitotic chromosome scaffold. We have previously proposed a similar stabilizing role for bamacan in the basement membrane matrix...

  2. Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood-brain barrier

    DEFF Research Database (Denmark)

    Thomsen, Maj Schneider; Birkelund, Svend; Burkhart, Annette;


    basement membrane proteins such as laminin-411, laminin-511, collagen IV [α1(IV)2 α2(IV)], agrin, perlecan, and nidogen 1 and 2 in vitro. Increased expression of the laminin α5 subunit correlated to the addition of BBB inducing factors (hydrocortisone, Ro 20-1724, and pCPT-cAMP), whereas increased...... expression of collagen IV α1 primarily correlated to increased levels of cAMP. In conclusion, BCECs cultured in vitro coherently form a BBB and express basement membrane proteins as a feature of maturation. This article is protected by copyright. All rights reserved....

  3. Sequential development of pulmonary hemorrhage with MPO-ANCA complicating anti-glomerular basement membrane antibody-mediated glomerulonephritis. (United States)

    Peces, R; Rodríguez, M; Pobes, A; Seco, M


    We report a case of rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 67-year-old woman with diabetes. Intensive combined immunosuppressive therapy with methylprednisolone bolus, oral prednisone, and cyclophosphamide led to negativity of anti-GBM antibodies but was not able to restore renal function. After 28 months of hemodialysis, the patient suddenly presented with pulmonary hemorrhage. In this setting, high levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and negative anti-GBM antibodies were found. Therapy with oral prednisone and cyclophosphamide led to resolution of pulmonary hemorrhage and negativity of MPO-ANCA.

  4. Creatinine clearance, urinary excretion of glomerular basement membrane antigens and renal histology in congenital nephrotic syndrome of Finnish type. (United States)

    Huttunen, N P


    The endogenous creatinine clearance and urinary excretion rate of glomerular basement membrane (GBM) antigens were followed from 2 to 19 months in fifteen patients with congenital nephrotic syndrome (CNF). The quantitative examination of renal morphology was made on fourteen of these patients. Creatinine clearance increased during the first few months of life and thereafter gradually decreased. The urinary excretion rate of GBM antigens rose during the course of the disease. The creatinine clearance did not correlate significantly with glomerular fibrosis but it did correlate with tubular atrophy and interstitial fibrosis. The urinary excretion of GBM antigens correlated significantly with glomerular and interstitial fibrosis and with tubular atrophy. It is concluded that there is a clear progress in the disease and the renal histological changes probably are caused by accumulation of GBM material in glomeruli.

  5. Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury

    DEFF Research Database (Denmark)

    Nielsen, M J; Karsdal, Morten A; Kazankov, K


    . AIM: To investigate whether differences in extracellular matrix (ECM) composition of the liver during fibrogenesis in two seemingly similar types of viral hepatitis could be reflected by differences in ECM turnover. METHODS: Utilising a cross-sectional design, we measured specific ECM protein...... fragments in plasma from 197 chronic hepatitis B (CHB) patients and 403 chronic hepatitis C (CHC) patients matched for inflammation grade and fibrosis stage. Markers of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3, P4NP7S...... and fibrosis only in CHC. Basement membrane collagen fragments P4NP7S and C4M were significantly higher in matched activity and fibrosis cohorts within CHB vs CHC. CONCLUSION: The main parameters to determine extracellular matrix biomarker levels are inflammation, fibrosis, and type of viral insult. Compared...

  6. Elastase, but not proteinase 3 (PR3), induces proteinuria associated with loss of glomerular basement membrane heparan sulphate after in vivo renal perfusion in rats

    NARCIS (Netherlands)

    Heeringa, P; VanDenBorn, J; Brouwer, E; Dolman, KM; Klok, PA; Huitema, MG; Limburg, PC; Bakker, MAH; Berden, JHM; Daha, MR; Kallenberg, CGM


    Elastase, but not PR3, induces proteinuria associated with loss of glomerular basement membrane (GEM) heparan sulphate after in vivo renal perfusion in rats. PR3 and elastase are cationic neutral serine proteinases present in the azurophilic granules of polymorphonuclear leucocytes. Release of these


    NARCIS (Netherlands)



    Histones can mediate the binding of DNA and anti-DNA to the glomerular basement membrane (GBM). Zn ELISA histone/DNA/anti-DNA complexes are able to bind to heparan sulfate (HS), an intrinsic constituent of the GBM. We questioned whether histone containing immune complexes are able to bind to the GBM

  8. 19-DEJ-1, a hemidesmosome-anchoring filament complex-associated monoclonal antibody. Definition of a new skin basement membrane antigenic defect in junctional and dystrophic epidermolysis bullosa

    DEFF Research Database (Denmark)

    Fine, J D; Horiguchi, Y; Couchman, J R


    A murine monoclonal antibody (19-DEJ-1) was recently produced that recognizes a unique antigenic epitope of human skin basement membrane localized to the midlamina lucida exclusively in those areas bordered by overlying hemidesmosomes. To determine whether the antigen defined by 19-DEJ-1 is norma...

  9. Distribution, ultrastructural localization, and ontogeny of the core protein of a heparan sulfate proteoglycan in human skin and other basement membranes

    DEFF Research Database (Denmark)

    Horiguchi, Y; Couchman, J R; Ljubimov, A V;


    A variety of heparan sulfate proteoglycans (HSPG) have been identified on cell surfaces and in basement membrane (BM). To more fully characterize HSPG in human skin BM, we used two monoclonal antibodies (MAb) directed against epitopes of the core protein of a high molecular weight HSPG isolated...

  10. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy. (United States)

    Moon, Pyong-Gon; Lee, Jeong-Eun; You, Sungyong; Kim, Taek-Kyun; Cho, Ji-Hoon; Kim, In-San; Kwon, Tae-Hwan; Kim, Chan-Duck; Park, Sun-Hee; Hwang, Daehee; Kim, Yong-Lim; Baek, Moon-Chang


    To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin-digested using a gel-assisted protocol, and quantified by label-free LC-MS/MS, using an MS(E) mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α-1-antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi-quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level.

  11. A direct contact between astrocyte and vitreous body is possible in the rabbit eye due to discontinuities in the basement membrane of the retinal inner limiting membrane

    Directory of Open Access Journals (Sweden)

    A. Haddad


    Full Text Available Different from most mammalian species, the optic nerve of the rabbit eye is initially formed inside the retina where myelination of the axons of the ganglion cells starts and vascularization occurs. Astrocytes are confined to these regions. The aforementioned nerve fibers known as medullated nerve fibers form two bundles that may be identified with the naked eye. The blood vessels run on the inner surface of these nerve fiber bundles (epivascularization and, accordingly, the accompanying astrocytes lie mostly facing the vitreous body from which they are separated only by the inner limiting membrane of the retina. The arrangement of the astrocytes around blood vessels leads to the formation of structures known as glial tufts. Fragments (N = 3 or whole pieces (N = 3 of the medullated nerve fiber region of three-month-old male rabbits (Orictolagus cuniculus were fixed in glutaraldehyde followed by osmium tetroxide, and their thin sections were examined with a transmission electron microscope. Randomly located discontinuities (up to a few micrometers long of the basement membrane of the inner limiting membrane of the retina were observed in the glial tufts. As a consequence, a direct contact between the astrocyte plasma membrane and vitreous elements was demonstrated, making possible functional interactions such as macromolecular exchanges between this glial cell type and the components of the vitreous body.

  12. Impact of ischemia-reperfusion on extracellular matrix processing and structure of the basement membrane of the heart.

    Directory of Open Access Journals (Sweden)

    Alexander Lauten

    Full Text Available PURPOSE: Acute ischemic injury is a strong inductor of cardiac remodelling, resulting in structural changes of the extracellular matrix (ECM and basement membrane (BM. In a large animal model of ischemia-reperfusion (I/R we investigated the post-ischemic liberation of the collagen-IV-fragments Tumstatin (TUM; 28 kDa-fragment of collagen-IV-alpha-3, Arresten (ARR; 26 kDa-fragment of collagen-IV-alpha-1 and Endorepellin (LG3, 85 kDa-fragment of perlecan which are biologically active in angiogenesis and vascularization in the post-ischemic myocardium. METHODS AND RESULTS: In this blinded study, 30 pigs were randomized to 60 min of global I/R at either 4°C or 32°C or served as control. Three transmyocardial tissue samples were collected prior to ischemia and within 30 min and 150 min of reperfusion. Tissue content of TUM, ARR and LG3 was analyzed by western blotting and immunostaining. Within 150 min of mild hypothermic I/R a significantly increased tissue content of ARR (0.17±0.14 vs. 0.56±0.56; p = 0.001 and LG3 (1.13±0.34 vs. 2.51±1.71, p11fold elevation of creatine kinase (2075±2595 U/l vs. 23248±6551 U/l; p<0.001 in the coronary sinus plasma samples. Immunostaining demonstrated no changes for ARR and LG3 presentation irrespective of temperature. In contrast, TUM significantly decreased in the BM surrounding cardiomyocytes and capillaries after mild and deep hypothermic I/R, thus representing structural alterations of the BM in these groups. CONCLUSION: The study demonstrates an early temperature-dependent processing of Col-IV as major component of the BM of cardiomyocytes and vascular endothelium. These observations support the protective effects of deep hypothermia during I/R. Furthermore, the results suggest an increased structural remodelling of the myocardial basement membrane with potential functional impairment during mild hypothermic I/R which may contribute to the progression to post-ischemic heart failure.

  13. Synthesis and localization of two sulphated glycoproteins associated with basement membranes and the extracellular matrix

    DEFF Research Database (Denmark)

    Hogan, B L; Taylor, A; Kurkinen, M;


    Two sulphated glycoproteins (sgps) of apparent molecular weight (Mr) 180,000 and 150,000, are synthesized by murine PYS and PF HR9 parietal endoderm and Swiss 3T3 cells. The Mr 150,000 sgp has a similar chemical structure to the sulphated glycoprotein, C, synthesized and laid down in Reichert......'s membrane by mouse embryo parietal endoderm cells (Hogan, B. L.M., A. Taylor, and A.R. Cooper, 1982, Dev. Biol., 90:210-214). Both the Mr 180,000 and 150,000 sgps are deposited in the detergent-insoluble matrix of cultured cells, but they do not apparently undergo any disulphide-dependent intermolecular...

  14. Comprehensive Characterization of Glycosylation and Hydroxylation of Basement Membrane Collagen IV by High-Resolution Mass Spectrometry. (United States)

    Basak, Trayambak; Vega-Montoto, Lorenzo; Zimmerman, Lisa J; Tabb, David L; Hudson, Billy G; Vanacore, Roberto M


    Collagen IV is the main structural protein that provides a scaffold for assembly of basement membrane proteins. Posttranslational modifications such as hydroxylation of proline and lysine and glycosylation of lysine are essential for the functioning of collagen IV triple-helical molecules. These modifications are highly abundant posing a difficult challenge for in-depth characterization of collagen IV using conventional proteomics approaches. Herein, we implemented an integrated pipeline combining high-resolution mass spectrometry with different fragmentation techniques and an optimized bioinformatics workflow to study posttranslational modifications in mouse collagen IV. We achieved 82% sequence coverage for the α1 chain, mapping 39 glycosylated hydroxylysine, 148 4-hydroxyproline, and seven 3-hydroxyproline residues. Further, we employed our pipeline to map the modifications on human collagen IV and achieved 85% sequence coverage for the α1 chain, mapping 35 glycosylated hydroxylysine, 163 4-hydroxyproline, and 14 3-hydroxyproline residues. Although lysine glycosylation heterogeneity was observed in both mouse and human, 21 conserved sites were identified. Likewise, five 3-hydroxyproline residues were conserved between mouse and human, suggesting that these modification sites are important for collagen IV function. Collectively, these are the first comprehensive maps of hydroxylation and glycosylation sites in collagen IV, which lay the foundation for dissecting the key role of these modifications in health and disease.

  15. Acute podocyte injury is not a stimulus for podocytes to migrate along the glomerular basement membrane in zebrafish larvae (United States)

    Siegerist, Florian; Blumenthal, Antje; Zhou, Weibin; Endlich, Karlhans; Endlich, Nicole


    Podocytes have a unique 3D structure of major and interdigitating foot processes which is the prerequisite for renal blood filtration. Loss of podocytes leads to chronic kidney disease ending in end stage renal disease. Until now, the question if podocytes can be replaced by immigration of cells along the glomerular basement membrane (GBM) is under debate. We recently showed that in contrast to former theories, podocytes are stationary in the zebrafish pronephros and neither migrate nor change their branching pattern of major processes over 23 hours. However, it was still unclear whether podocytes are able to migrate during acute injury. To investigate this, we applied the nitroreductase/metronidazole zebrafish model of podocyte injury to in vivo two-photon microscopy. The application of metronidazole led to retractions of major processes associated with a reduced expression of podocyte-specific proteins and a formation of subpodocyte pseudocyst. Electron microscopy showed that broad areas of the capillaries became denuded. By 4D in vivo observation of single podocytes, we could show that the remaining podocytes did not walk along GBM during 24 h. This in vivo study reveals that podocytes are very stationary cells making regenerative processes by podocyte walking along the GBM very unlikely. PMID:28252672

  16. Complement and Humoral Adaptive Immunity in the Human Choroid Plexus: Roles for Stromal Concretions, Basement Membranes, and Epithelium. (United States)

    Moore, G R Wayne; Laule, Cornelia; Leung, Esther; Pavlova, Vladimira; Morgan, B Paul; Esiri, Margaret M


    The choroid plexus (CP) provides a barrier to entry of toxic molecules from the blood into the brain and transports vital molecules into the cerebrospinal fluid. While a great deal is known about CP physiology, relatively little is known about its immunology. Here, we show immunohistochemical data that help define the role of the CP in innate and adaptive humoral immunity. The results show that complement, in the form of C1q, C3d, C9, or C9neo, is preferentially deposited in stromal concretions. In contrast, immunoglobulin (Ig) G (IgG) and IgA are more often found in CP epithelial cells, and IgM is found in either locale. C4d, IgD, and IgE are rarely, if ever, seen in the CP. In multiple sclerosis CP, basement membrane C9 or stromal IgA patterns were common but were not specific for the disease. These findings indicate that the CP may orchestrate the clearance of complement, particularly by deposition in its concretions, IgA and IgG preferentially via its epithelium, and IgM by either mechanism.

  17. Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Muller H Konrad


    Full Text Available Abstract Background Little is known about airway remodelling in bronchial biopsies (BB in smokers and chronic obstructive pulmonary disease (COPD. We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm fragmentation and altered vessel distribution in COPD. Methods To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects. Results Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p Conclusions Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.

  18. Skin Basement Membrane: The Foundation of Epidermal Integrity—BM Functions and Diverse Roles of Bridging Molecules Nidogen and Perlecan

    Directory of Open Access Journals (Sweden)

    Dirk Breitkreutz


    Full Text Available The epidermis functions in skin as first defense line or barrier against environmental impacts, resting on extracellular matrix (ECM of the dermis underneath. Both compartments are connected by the basement membrane (BM, composed of a set of distinct glycoproteins and proteoglycans. Herein we are reviewing molecular aspects of BM structure, composition, and function regarding not only (i the dermoepidermal interface but also (ii the resident microvasculature, primarily focusing on the per se nonscaffold forming components perlecan and nidogen-1 and nidogen-2. Depletion or functional deficiencies of any BM component are lethal at some stage of development or around birth, though BM defects vary between organs and tissues. Lethality problems were overcome by developmental stage- and skin-specific gene targeting or by cell grafting and organotypic (3D cocultures of normal or defective cells, which allows recapitulating BM formation de novo. Thus, evidence is accumulating that BM assembly and turnover rely on mechanical properties and composition of the adjacent ECM and the dynamics of molecular assembly, including further “minor” local components, nidogens largely functioning as catalysts or molecular adaptors and perlecan as bridging stabilizer. Collectively, orchestration of BM assembly, remodeling, and the role of individual players herein are determined by the developmental, tissue-specific, or functional context.

  19. Efficient differentiation of embryonic stem cells into hepatic cells in vitro using a feeder-free basement membrane substratum.

    Directory of Open Access Journals (Sweden)

    Nobuaki Shiraki

    Full Text Available The endoderm-inducing effect of the mesoderm-derived supportive cell line M15 on embryonic stem (ES cells is partly mediated through the extracellular matrix, of which laminin α5 is a crucial component. Mouse ES or induced pluripotent stem cells cultured on a synthesized basement membrane (sBM substratum, using an HEK293 cell line (rLN10-293 cell stably expressing laminin-511, could differentiate into definitive endoderm and subsequently into pancreatic lineages. In this study, we investigated the differentiation on sBM of mouse and human ES cells into hepatic lineages. The results indicated that the BM components played an important role in supporting the regional-specific differentiation of ES cells into hepatic endoderm. We show here that knockdown of integrin β1 (Itgb1 in ES cells reduced their differentiation into hepatic lineages and that this is mediated through Akt signaling activation. Moreover, under optimal conditions, human ES cells differentiated to express mature hepatocyte markers and secreted high levels of albumin. This novel procedure for inducing hepatic differentiation will be useful for elucidating the molecular mechanisms controlling lineage-specific fates during gut regionalization. It could also represent an attractive approach to providing a surrogate cell source, not only for regenerative medicine, but also for pharmaceutical and toxicologic studies.

  20. Comparative analysis of fibrillar and basement membrane collagen expression in embryos of the sea urchin, Strongylocentrotus purpuratus. (United States)

    Suzuki, H R; Reiter, R S; D'Alessio, M; Di Liberto, M; Ramirez, F; Exposito, J Y; Gambino, R; Solursh, M


    The time of appearance and location of three distinct collagen gene transcripts termed 1 alpha, 2 alpha, and 3 alpha, were monitored in the developing S. purpuratus embryo by in situ hybridization. The 1 alpha and 2 alpha transcripts of fibrillar collagens were detected simultaneously in the primary (PMC) and secondary (SMC) mesenchyme cells of the late gastrula stage and subsequently expressed in the spicules and gut associated cells of the pluteus stage. The 3 alpha transcripts of the basement membrane collagen appeared earlier than 1 alpha and 2 alpha, and were first detected in the presumptive PMC at the vegetal plate of the late blastula stage. The PMC exhibited high expression of 3 alpha at the mesenchyme blastula stage, but during gastrulation the level of expression was reduced differentially among the PMC. In the late gastrula and pluteus stages, both PMC and SMC expressed 3 alpha mRNA, and thus at these stages all three collagen genes displayed an identical expression pattern by coincidence. This study thus provides the first survey of onset and localization of multiple collagen transcripts in a single sea urchin species.

  1. Reorganization of endothelial cord-like structures on basement membrane complex (Matrigel): involvement of transforming growth factor beta 1. (United States)

    Kuzuya, M; Kinsella, J L


    The formation of capillary-like network structures by cultured vascular endothelial cells on reconstituted basement membrane matrix, Matrigel, models endothelial cell differentiation, the final step of angiogenesis (Kubota et al., 1988; Grant et al., 1989). When endothelial cells derived from bovine aorta and brain capillaries were plated on Matrigel, DNA synthesis was suppressed and a network of capillary-like structures rapidly formed in 8-12 h. With time, the network broke down, resulting in dense cellular cords radiating from multiple cellular clusters in 16-24 h. Finally, multicellular aggregates of cells were formed as the network underwent further retraction. Network regression was prevented when either dithiothreitol (DTT) or anti-TGF-beta 1 antibodies were added during the assay. The addition of exogenous TGF-beta 1 promoted the regression of endothelial cells into the clusters. This response to TGF-beta 1 was blocked by potent serine threonine protein kinase inhibitors, H-7 and HA100. TGF-beta 1 was released from polymerized Matrigel by incubation with Dulbecco's modified eagle's medium (DMEM) in the absence of cells. The Matrigel-conditioned DMEM inhibited endothelial DNA synthesis even in the presence of anti-TGF-beta 1 antibodies. These results suggest that TGF-beta 1 and possibly other soluble factors from Matrigel may be important for differentiation and remodeling of endothelial cells in a capillary network with possible implications for wound healing and development.

  2. Anti-Glomerular Basement Membrane Disease Combined with IgA Nephropathy Complicated with Reversible Posterior Leukoencephalopathy Syndrome: An Unusual Case (United States)

    Ge, Ya-ting; Liao, Jin-lan; Liang, Wei; Xiong, Zu-ying


    Patient: Male, 24 Final Diagnosis: Crescentic glomerulonephritis (type I) with IgA nephropathy Symptoms: Headache • gross hematuria • nocturia • seizures Medication: Cyclophosphamide Clinical Procedure: Dignosis to treatment Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Anti-glomerular basement membrane disease (anti-GBM disease) is an autoimmune glomerulonephritis disease that is characterized by IgG linear deposition along the non-collagen domain of α3 chains of type IV collagen on the GBM. Although anti-GBM disease accompanied with IgA linear deposition along GBMs was discussed previously in some papers, anti-GBM disease combined with IgA granular deposition in the mesangial area, especially complicated with reversible posterior leukoencephalopathy syndrome (RPLS), was rarely reported. RPLS is usually caused by hypertensive encephalopathy, renal decompensation, fluid retention, and adverse effects of immunosuppressive drugs. Case Report: A male patient with the chief complaints of headache, gross hematuria, and nocturia was referred to our hospital. Based on renal biopsy, the diagnosis was finally confirmed as anti-GBM disease combined with IgA nephropathy and, the patient received comprehensive treatment, including cyclophosphamide (CTX), which led to symptom improvement. Two days after the third impulse CTX was given, he suddenly experienced headache and dizziness, which eventually developed into a tonic-clonic seizure. RPLS was identified by cranial magnetic resonance imaging (MRI) with reversible neuroimaging. After diazepam and antihypertension management, seizures were controlled. RPLS, a neurological complication, was found in anti-GBM disease with IgA nephropathy during our immunosuppressants therapy for the first time. Conclusions: It is worth paying more attention to patients with rapidly progressive glomerulonephritis (RPGN), as they might be complicated with RPLS during intravenous administration of CTX

  3. Increased initiation and growth of tumor cell lines, cancer stem cells and biopsy material in mice using basement membrane matrix protein (Cultrex or Matrigel) co-injection. (United States)

    Fridman, Rafael; Benton, Gabriel; Aranoutova, Irina; Kleinman, Hynda K; Bonfil, R Daniel


    This protocol requires 2-4 h and presents a method for injecting tumor cells, cancer stem cells or dispersed biopsy material into subcutaneous or orthotopic locations within recipient mice. The tumor cells or biopsy are mixed with basement membrane matrix proteins (CultrexBME or Matrigel) at 4 °C and then injected into recipient animals at preferred anatomical sites. Tumor cells can also be co-injected with additional cell types, such as fibroblasts, stromal cells, endothelial cells and so on. Details are given on appropriate cell numbers, handling and concentration of the basement membrane proteins, recipient animals, injection location and techniques. This procedure enables the growth of tumors from cells or biopsy material (tumor graft) with greater efficiency of take and growth, and with retention of the primary tumor phenotype based on histology. Co-injection with additional cell types provides more physiological models of human cancers for use in drug screening and studying cancer biology.

  4. Subepithelial basement membrane thickness in patients with normal colonic mucosal appearance in colonoscopy:Results from southern Turkey

    Institute of Scientific and Technical Information of China (English)

    Fazilet Kayaselcuk; Ender Serin; Yǖksel Gumurdulu; Birol Ozer; Ilhan Tuncer; Sedat Boyacioglu


    AIM: Our aims were to determine the normal limits of subepithelial basement membrane (SEBM) thickness in order to more accurately diagnose collagenous colitis in the population from southern Turkey and to investigate into links between SEBM thickness and age, and sex.METHODS: The study included 100 patients (mean age 50.0±13.3 years; male, 34; female, 66) with miscellaneous gastrointestinal symptoms, and normal colonic mucosal appearance in colonoscopic evaluation. Biopsies were taken from five different regions of the colon. SEBM was measured with a calibrated eyepiece on specimens prepared with specific stains for collagen. Intensity of inflammatory cells was graded semiquantitatively. Differences in SEBM thickness among the different colon regions, and relationships between SEBM thickness and age, sex, and density of inflammatory cells were statistically evaluated.RESULTS: The cecum and rectum showed the largest amounts of infiltrate. None of the specimens showed histologic findings of collagenous colitis. The SEBM thicknesses measured for each case ranged from 3-20 μm. The biggest thickness was observed in rectal mucosa (median value: 10 μm).Cecum and ascending colon showed similar SEBM thickness (median value: 5 μm). SEBM thickness was not correlated with patient age or sex, but was positively correlated with the intensity of inflammatory cells in each colon segment.CONCLUSION: In this patient group from southern Turkey,SEBM was thickest in the rectum. Our results indicate that,in this population, SEBM thickness is not correlated with age or sex, but is positively correlated with severity of inflammation. The findings also support the concept that measuring SEBM thickness at one segment in the colon is inadequate and may be misleading.

  5. Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish. (United States)

    Takeuchi, Miki; Yamaguchi, Shingo; Yonemura, Shigenobu; Kakiguchi, Kisa; Sato, Yoshikatsu; Higashiyama, Tetsuya; Shimizu, Takashi; Hibi, Masahiko


    Granule cells (GCs) are the major glutamatergic neurons in the cerebellum, and GC axon formation is an initial step in establishing functional cerebellar circuits. In the zebrafish cerebellum, GCs can be classified into rostromedial and caudolateral groups, according to the locations of their somata in the corresponding cerebellar lobes. The axons of the GCs in the caudolateral lobes terminate on crest cells in the dorsal hindbrain, as well as forming en passant synapses with Purkinje cells in the cerebellum. In the zebrafish mutant shiomaneki, the caudolateral GCs extend aberrant axons. Positional cloning revealed that the shiomaneki (sio) gene locus encodes Col4a6, a subunit of type IV collagen, which, in a complex with Col4a5, is a basement membrane (BM) component. Both col4a5 and col4a6 mutants displayed similar abnormalities in the axogenesis of GCs and retinal ganglion cells (RGCs). Although type IV collagen is reported to control axon targeting by regulating the concentration gradient of an axonal guidance molecule Slit, Slit overexpression did not affect the GC axons. The structure of the BM surrounding the tectum and dorsal hindbrain was disorganized in the col4a5 and col4a6 mutants. Moreover, the abnormal axogenesis of the caudolateral GCs and the RGCs was coupled with aberrant BM structures in the type IV collagen mutants. The regrowth of GC axons after experimental ablation revealed that the original and newly formed axons displayed similar branching and extension abnormalities in the col4a6 mutants. These results collectively suggest that type IV collagen controls GC axon formation by regulating the integrity of the BM, which provides axons with the correct path to their targets.

  6. Laminin and type IV collagen isoform substitutions occur in temporally and spatially distinct patterns in developing kidney glomerular basement membranes. (United States)

    Abrahamson, Dale R; St John, Patricia L; Stroganova, Larysa; Zelenchuk, Adrian; Steenhard, Brooke M


    Kidney glomerular basement membranes (GBMs) undergo laminin and type IV collagen isoform substitutions during glomerular development, which are believed to be required for maturation of the filtration barrier. Specifically, GBMs of earliest glomeruli contain laminin α1β1γ1 and collagen α1α2α1(IV), whereas mature glomeruli contain laminin α5β2γ1 and collagen α3α4α5(IV). Here, we used confocal microscopy to simultaneously evaluate expression of different laminin and collagen IV isoforms in newborn mouse GBMs. Our results show loss of laminin α1 from GBMs in early capillary loop stages and continuous linear deposition of laminin bearing the α5 chain thereafter. In contrast, collagen α1α2α1(IV) persisted in linear patterns into late capillary loop stages, when collagen α3α4α5(IV) first appeared in discontinuous, non-linear patterns. This patchy pattern for collagen α3α4α5(IV) continued into maturing glomeruli where there were lengths of linear, laminin α5-positive GBM entirely lacking either isoform of collagen IV. Relative abundance of laminin and collagen IV mRNAs in newborn and 5-week-old mouse kidneys also differed, with those encoding laminin α1, α5, β1, β2, and γ1, and collagen α1(IV) and α2(IV) chains all significantly declining at 5 weeks, but α3(IV) and α4(IV) were significantly upregulated. We conclude that different biosynthetic mechanisms control laminin and type IV collagen expression in developing glomeruli.

  7. Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers. (United States)

    Mori, Taizo; Kariya, Yoshinobu; Komiya, Eriko; Higashi, Shouichi; Miyagi, Yohei; Sekiguchi, Kiyotoshi; Miyazaki, Kaoru


    Laminins present in the basement membranes (BM) of blood vessels are involved in angiogenesis and other vascular functions that are critical for tumor growth and metastasis. Two major vascular laminins, the α4 (laminin-411/421) and α5 (laminin-511/521) types, have been well characterized. We recently found a third type of vascular laminin, laminin-3B11, consisting of the α3B, β1 and γ1 chains, and revealed its biological activity. Laminin-3B11 potently stimulates vascular endothelial cells to extend lamellipodial protrusions. To understand the roles of laminin-3B11 in blood vessel functions and tumor growth, we examined localization of the laminin α3B chain in normal mammary glands and breast cancers, in comparison with the α4 and α5 laminins. In the immunohistochemical analysis, the α3B laminin was co-localized with the α4 and α5 laminins in the BM of venules and capillaries of normal breast tissues, but α3B was scarcely detected in vessels near invasive breast carcinoma cells. In contrast, the α4 laminin was overexpressed in capillaries of invasive carcinomas, where a large number of macrophages were found. The α5 laminin appeared to be weakly downregulated in cancer tissues, especially in capillary vessels. Furthermore, our in vitro analysis indicated that TNF-α significantly suppressed the laminin α3B expression in vascular endothelial cells, while it, as well as IL-1β and TGF-α, upregulated the α4 expression. These results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis.

  8. Linear IgA bullous disease with possible immunoreactivity to the basement membrane zone and dermal blood vessels

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez


    Full Text Available Introduction: Linear IgA bullous dermatosis (LAD is an immunobullous disorder, in which IgA antibodies are deposited along the basement membrane zone (BMZ of the skin in a linear pattern. The cause of this disease is unknown, but the eruption may occur more commonly in association with certain medications. Case report: A 61 year old woman presented with blisters in the axillae and legs, with pain, itching and swelling. She was taking many medications for other conditions such diabetes and obesity. Tense blisters were seen, primarily on the legs and accompanied by some ankle swelling. Methods: Skin biopsies for hematoxylin and eosin (H&E examination, as well as for direct immunofluorescence (DIF, and immunohistochemistry (IHC studies were performed. Results: The H&E examination revealed a subepidermal blister, with small numbers of lymphocytes, neutrophils and eosinophils noted within the blister lumen. The dermis also displayed a mild, superficial, perivascular infiltrate of lymphocytes and histiocytes; eosinophils and neutrophils were also noted. DIF and IHC studies confirmed the diagnosis of linear IgA (LAD at the BMZ. However, in addition to immunoglobulin A, we also observed deposits of IgA, IgM, IgG, IgD, Kappa, Lambda, Complement/C3c, C1q, fibrinogen and albumin around upper dermal blood vessels. Conclusions: LAD has been most commonly associated with medication intake; the most common DIF immune response is the presence of linear IgA at the BMZ. However, here we found additional reactivity to against dermal blood vessels. Because the patient is affected by diabetes mellitus, it is difficult to know if the observed vascular reactivity was associated with the diabetes or solely an immune reaction to the vessels. Based on our findings, we encourage searching for vascular reactivity in cases of LAD.

  9. First Identification of a Triple Corneal Dystrophy Association: Keratoconus, Epithelial Basement Membrane Corneal Dystrophy and Fuchs' Endothelial Corneal Dystrophy

    Directory of Open Access Journals (Sweden)

    Cosimo Mazzotta


    Full Text Available Purpose: To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC, epithelial basement membrane corneal dystrophy (EBMCD and Fuchs' endothelial corneal dystrophy (FECD. Methods: A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing. Results: Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1. Conclusion: This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.

  10. Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Miki Takeuchi


    Full Text Available Granule cells (GCs are the major glutamatergic neurons in the cerebellum, and GC axon formation is an initial step in establishing functional cerebellar circuits. In the zebrafish cerebellum, GCs can be classified into rostromedial and caudolateral groups, according to the locations of their somata in the corresponding cerebellar lobes. The axons of the GCs in the caudolateral lobes terminate on crest cells in the dorsal hindbrain, as well as forming en passant synapses with Purkinje cells in the cerebellum. In the zebrafish mutant shiomaneki, the caudolateral GCs extend aberrant axons. Positional cloning revealed that the shiomaneki (sio gene locus encodes Col4a6, a subunit of type IV collagen, which, in a complex with Col4a5, is a basement membrane (BM component. Both col4a5 and col4a6 mutants displayed similar abnormalities in the axogenesis of GCs and retinal ganglion cells (RGCs. Although type IV collagen is reported to control axon targeting by regulating the concentration gradient of an axonal guidance molecule Slit, Slit overexpression did not affect the GC axons. The structure of the BM surrounding the tectum and dorsal hindbrain was disorganized in the col4a5 and col4a6 mutants. Moreover, the abnormal axogenesis of the caudolateral GCs and the RGCs was coupled with aberrant BM structures in the type IV collagen mutants. The regrowth of GC axons after experimental ablation revealed that the original and newly formed axons displayed similar branching and extension abnormalities in the col4a6 mutants. These results collectively suggest that type IV collagen controls GC axon formation by regulating the integrity of the BM, which provides axons with the correct path to their targets.

  11. The Alteration of the Epidermal Basement Membrane Complex of Human Nevus Tissue and Keratinocyte Attachment after High Hydrostatic Pressurization

    Directory of Open Access Journals (Sweden)

    Naoki Morimoto


    Full Text Available We previously reported that human nevus tissue was inactivated after high hydrostatic pressure (HHP higher than 200 MPa and that human cultured epidermis (hCE engrafted on the pressurized nevus at 200 MPa but not at 1000 MPa. In this study, we explore the changes to the epidermal basement membrane in detail and elucidate the cause of the difference in hCE engraftment. Nevus specimens of 8 mm in diameter were divided into five groups (control and 100, 200, 500, and 1000 MPa. Immediately after HHP, immunohistochemical staining was performed to detect the presence of laminin-332 and type VII collagen, and the specimens were observed by transmission electron microscopy (TEM. hCE was placed on the pressurized nevus specimens in the 200, 500, and 1000 MPa groups and implanted into the subcutis of nude mice; the specimens were harvested at 14 days after implantation. Then, human keratinocytes were seeded on the pressurized nevus and the attachment was evaluated. The immunohistochemical staining results revealed that the control and 100 MPa, 200 MPa, and 500 MPa groups were positive for type VII collagen and laminin-332 immediately after HHP. TEM showed that, in all of the groups, the lamina densa existed; however, anchoring fibrils were not clearly observed in the 500 or 1000 MPa groups. Although the hCE took in the 200 and 500 MPa groups, keratinocyte attachment was only confirmed in the 200 MPa group. This result indicates that HHP at 200 MPa is preferable for inactivating nevus tissue to allow its reuse for skin reconstruction in the clinical setting.

  12. Fibrillar, fibril-associated and basement membrane collagens of the arterial wall: architecture, elasticity and remodeling under stress. (United States)

    Osidak, M S; Osidak, E O; Akhmanova, M A; Domogatsky, S P; Domogatskaya, A S


    The ability of a human artery to pass through 150 million liters of blood sustaining 2 billion pulsations of blood pressure with minor deterioration depends on unique construction of the arterial wall. Viscoelastic properties of this construction enable to re-seal the occuring damages apparently without direct immediate participance of the constituent cells. Collagen structures are considered to be the elements that determine the mechanoelastic properties of the wall in parallel with elastin responsible for elasticity and resilience. Collagen scaffold architecture is the function-dependent dynamic arrangement of a dozen different collagen types composing three distinct interacting forms inside the extracellular matrix of the wall. Tightly packed molecules of collagen types I, III, V provide high tensile strength along collagen fibrils but toughness of the collagen scaffold as a whole depends on molecular bonds between distinct fibrils. Apart of other macromolecules in the extracellular matrix (ECM), collagen-specific interlinks involve microfilaments of collagen type VI, meshwork-organized collagen type VIII, and FACIT collagen type XIV. Basement membrane collagen types IV, XV, XVIII and cell-associated collagen XIII enable transmission of mechanical signals between cells and whole artery matrix. Collagen scaffold undergoes continuous remodeling by decomposition promoted with MMPs and reconstitution from newly produced collagen molecules. Pulsatile stress-strain load modulates both collagen synthesis and MMP-dependent collagen degradation. In this way the ECM structure becomes adoptive to mechanical challenges. The mechanoelastic properties of the arterial wall are changed in atherosclerosis concomitantly with collagen turnover both type-specific and dependent on the structure. Improving the feedback could be another approach to restore sufficient blood circulation.

  13. Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries from Patients with Type 2 Diabetes and Lower Levels among Metformin Users

    DEFF Research Database (Denmark)

    Rørdam Preil, Simone; Kristensen, Lars P; Beck, Hans C;


    BACKGROUND: -The increased risk of cardiovascular diseases (CVD) in type 2 diabetes has been extensively documented, but the origins of the association remain largely unknown. We sought to determine changes in protein expressions in arterial tissue from patients with type 2 diabetes and moreover...... hypothesized that metformin intake influences the protein composition. METHODS AND RESULTS: -We analyzed non-atherosclerotic repair arteries gathered at coronary by-pass operations from 30 patients with type 2 diabetes, as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome...... analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual arterial samples. The amounts of the basement membrane (BM) components, alpha-1- and alpha-2- type IV collagen, gamma-1- and beta-2-laminin were significantly increased in patients with diabetes. Moreover, the expressions of basement...

  14. Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane (United States)

    Gyoneva, Lazarina

    The glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is alpha3(IV)alpha4(IV)alpha5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the alpha3(IV)alpha4(IV)alpha5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the alpha3(IV)alpha4(IV)alpha5(IV) chains present and missing. The experiments showed basement membranes containing alpha3(IV)alpha4(IV)alpha5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the alpha3(IV)alpha4(IV)alpha5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the alpha3(IV)alpha4(IV)alpha5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the alpha3(IV)alpha4(IV)alpha5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of alpha3(IV)alpha4(IV

  15. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli


    Pitera JE, Scambler PJ, Woolf AS.


    FRAS1 is mutated in some individuals with Fraser syndrome (FS) and the encoded protein is expressed in embryonic epidermal cells, localizing in their basement membrane (BM). Syndactyly and cryptophthalmos in FS are sequelae of skin fragility but the bases for associated kidney malformations are unclear. We demonstrate that Fras1 is expressed in the branching ureteric bud (UB), and that renal agenesis occurs in homozygous Fras1 null mutant blebbed (bl) mice on a C57BL6J background. In vivo, th...

  16. MMP Mediated Degradation of Type IV Collagen Alpha 1 and Alpha 3 Chains Reflects Basement Membrane Remodeling in Experimental and Clinical Fibrosis - Validation of Two Novel Biomarker Assays

    DEFF Research Database (Denmark)

    Sand, Jannie Marie; Larsen, Lise Skakkebæk; Hogaboam, Cory;


    Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP) mediated degradation of type IV collagen, a main component of the basement membrane, will release...... peptide fragments (neo-epitopes) into the circulation. Here we present the development of two competitive enzyme-linked immunosorbent assays (ELISAs) for assessing the levels of specific fragments of type IV collagen α1 (C4M12a1) and α3 (C4M12a3) chains in serum as indicators of fibrosis....

  17. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition

    Energy Technology Data Exchange (ETDEWEB)

    Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Villadsen, Rene; Rank, Fritz; Bissell, Mina J.; Petersen, Ole William


    The signals that determine the correct polarity of breast epithelial structures in vivo are not understood. We have shown previously that luminal epithelial cells can be polarized when cultured within a reconstituted basement membrane gel. We reasoned that such cues in vivo may be given by myoepithelial cells. Accordingly, we used an assay where luminal epithelial cells are incorrectly polarized to test this hypothesis. We show that culturing human primary luminal epithelial cells within collagen-I gels leads to formation of structures with no lumina and with reverse polarity as judged by dual stainings for sialomucin, epithelial specific antigen or occludin. No basement membrane is deposited, and {beta}4-integrin staining is negative. Addition of purified human myoepithelial cells isolated from normal glands corrects the inverse polarity, and leads to formation of double-layered acini with central lumina. Among the laminins present in the human breast basement membrane (laminin-1, -5 and -10/11), laminin-1 was unique in its ability to substitute for myoepithelial cells in polarity reversal. Myoepithelial cells were purified also from four different breast cancer sources including a biphasic cell line. Three out of four samples either totally lacked the ability to interact with luminal epithelial cells, or conveyed only correction of polarity in a fraction of acini. This behavior was directly related to the ability of the tumor myoepithelial cells to produce {alpha}-1 chain of laminin. In vivo, breast carcinomas were either negative for laminin-1 (7/12 biopsies) or showed a focal, fragmented deposition of a less intensely stained basement membrane (5/12 biopsies). Dual staining with myoepithelial markers revealed that tumorassociated myoepithelial cells were either negative or weakly positive for expression of laminin-1, establishing a strong correlation between loss of laminin-1 and breast cancer. We conclude that the double-layered breast acinus may be

  18. Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne S.; Karsdal, Morten A.; Nawrocki, Arkadiusz


    by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA......Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens...... for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models....

  19. The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded

    Directory of Open Access Journals (Sweden)

    Tyagi Suresh C


    Full Text Available Abstract The vascular endothelial basement membrane and extra cellular matrix is a compilation of different macromolecules organized by physical entanglements, opposing ionic charges, chemical covalent bonding, and cross-linking into a biomechanically active polymer. These matrices provide a gel-like form and scaffolding structure with regional tensile strength provided by collagens, elasticity by elastins, adhesiveness by structural glycoproteins, compressibility by proteoglycans – hyaluronans, and communicability by a family of integrins, which exchanges information between cells and between cells and the extracellular matrix of vascular tissues. Each component of the extracellular matrix and specifically the capillary basement membrane possesses unique structural properties and interactions with one another, which determine the separate and combined roles in the multiple diabetic complications or diabetic opathies. Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel companion (atheroscleropathy are associated with multiple metabolic toxicities and chronic injurious stimuli. The adaptable quality of a matrix or form genetically preloaded with the necessary information to communicate and respond to an ever-changing environment, which supports the interstitium, capillary and arterial vessel wall is individually examined.

  20. β2 and γ3 laminins are critical cortical basement membrane components: ablation of Lamb2 and Lamc3 genes disrupts cortical lamination and produces dysplasia. (United States)

    Radner, Stephanie; Banos, Charles; Bachay, Galina; Li, Yong N; Hunter, Dale D; Brunken, William J; Yee, Kathleen T


    Cortical development is dependent on the timely production and migration of neurons from neurogenic sites to their mature positions. Mutations in several receptors for extracellular matrix (ECM) molecules and their downstream signaling cascades produce dysplasia in brain. Although mutation of a critical binding site in the gene that encodes the ECM molecule laminin γ1 (Lamc1) disrupts cortical lamination, the ECM ligand(s) for many ECM receptors have not been demonstrated directly in the cortex. Several isoforms of the heterotrimeric laminins, all containing the β2 and γ3 chain, have been isolated from the brain, suggesting they are important for CNS function. Here, we report that mice homozygous null for the laminin β2 and γ3 chains exhibit cortical laminar disorganization. Mice lacking both of these laminin chains exhibit hallmarks of human cobblestone lissencephaly (type II, nonclassical): they demonstrate severe laminar disruption; midline fusion; perturbation of Cajal-Retzius cell distribution; altered radial glial cell morphology; and ectopic germinal zones. Surprisingly, heterozygous mice also exhibit laminar disruption of cortical neurons, albeit with lesser severity. In compound null mice, the pial basement membrane is fractured, and the distribution of a key laminin receptor, dystroglycan, is altered. These data suggest that β2 and γ3-containing laminins play an important dose-dependent role in development of the cortical pial basement membrane, which serves as an attachment site for Cajal-Retzius and radial glial cells, thereby guiding neural development.

  1. The use of thermovision camera to observe physiological and pathological conditions of oral cavity mucous membrane (United States)

    Dąbrowski, M.; Dulski, R.; Żmuda, S.; Zaborowski, P.; Pogorzelski, C.


    This article presents initial results of investigations of the temperature distribution changes in oral cavity mucous membrane. The investigations aimed to prepare a model of temperature changes existing within mucosal membrane in physiological conditions and to compare those changes with those under pathological conditions. Our investigations were carried out using an infrared imaging system. A representative group of patients was tested.

  2. The Preliminary Report of Pathological Changes of Epiretinal Membranes and Internal Limiting Membrane Removed during Idiopathic Macular Hole Surgery

    Institute of Scientific and Technical Information of China (English)

    Jiaqing Li; Shibo Tang; Yan Luo; Jie Zhang; Shaofen Lin


    Purpose:To investigate the pathological changes of epiretinal membranes(ERM)and internal limiting membrane (ILM) removed during idiopathic macular hole surgery.Methods:Ten consecutive patients with a unilateral idiopathic macular hole underwent pars plana vitrectomy(PPV) with the surgical removal of the ERMs overlying the hole and ILM surrounding the hole. The pathological features of the excised tissues were examined under the microscope. Results:According to the morphological changes, four ERMs showed cellular elements which looked like glia cells, macrophages, plasma cells, lymphocytes and fibroblast cells. Two of the ILM appeared as transparent membranes without cellular elements. The other eight ILM showed cellular elements on the transparent membranes.Conclusion: Our study supports the hypothesis that the tangential traction of vitreous and proliferative cellular elements on the inner surface of ILM causes idiopathic macular holes. Removal of the posterior cortical vitreous, ILM and proliferative cellular tissue is a valid treatment for IMH.

  3. [Traumatic pathology of antibrachial interosseous membrane of forearm]. (United States)

    Soubeyrand, Marc; Lafont, Clarisse; De Georges, Renaud; Dumontier, Christian


    The antibrachial interosseous membrane (IOM) is taught over an average length of 10.6cm between the diaphyses of the radius and ulna bone. It looks like a stitch with fibers running from the ulna to the radius and from proximal to distal and fibers running from distal to proximal. The central band, which is the middle part of the fibers directed from distal to proximal has mechanical properties similar to those of a ligament and act as a ligamentous structure embedded in the larger membranous complex of the IOM. The interosseous membrane has a double function: it stabilizes transversally the forearm's two bones and stabilizes longitudinally the two bones by transferring loads from the radius to the ulna. Load transmission varies according to the prono-supination position, the varus-valgus constraints on the elbow and the inclination of the wrist, making interpretation of the experimental data difficult. One should consider the forearm as a whole and the interosseous membrane with the two diaphyses should be regarded as a middle radio-ulnar joint, intercalated between the proximal and distal radio-ulnar joint. Those three articulations or links between radius and ulna act synergistically to stabilize and optimize repartition of loads. Functional loss of one of these links, and of course of more than one, will severely modify the forearm function. Essex-Lopresti lesion, which represents the functional loss of all three links, is the most destabilizing forearm lesion. Imaging of the interosseous membrane is difficult. MRI allows for static imaging of the interosseous membrane but there are often artifacts due to previous trauma or surgical procedures. Dynamic sonography helps to visualize all the lesions and will probably be part of the evaluation of every severe forearm injury. Surgical treatment depends on the gravity of the lesions of the different links. Interosseous membrane reconstruction is still the most difficult technique and most of the previously reported

  4. Immunohistochemical localization of chondroitin sulfate, chondroitin sulfate proteoglycan, heparan sulfate proteoglycan, entactin, and laminin in basement membranes of postnatal developing and adult rat lungs

    DEFF Research Database (Denmark)

    Sannes, P L; Burch, K K; Khosla, J


    alveolar, airway, and vascular BMs, in addition to smooth muscle external laminae (EL), in the adult and developing rat. Immunostaining for CSPG required hyaluronidase digestion, whereas CS staining was lost with the same treatment. A polyclonal antibody to the core protein of HSPG was found...... to be similarly distributed to CSPG by immunoperoxidase staining in adult and developing rat lungs, with the notable exception that little immunoreactivity for HSPG was found in smooth muscle EL. Commercially obtained polyclonal antibodies to entactin and laminin gave immunostaining comparable to that seen......Histologic preparations of lungs from 1-, 5-, 10-, 18-, and 25-day-old postnatal and adult rats were examined immunohistochemically with antibodies specific against chondroitin sulfate (CS), basement membrane chondroitin sulfate proteoglycan (BM-CSPG), heparan sulfate proteoglycan (HSPG), entactin...

  5. In vitro blood-brain barrier models for drug research: state-of-the-art and new perspectives on reconstituting these models on artificial basement membrane platforms. (United States)

    Banerjee, Jayati; Shi, Yejiao; Azevedo, Helena S


    In vitro blood-brain barrier (BBB) models are indispensable screening tools for obtaining early information about the brain-penetrating behaviour of promising drug candidates. Until now, in vitro BBB models have focused on investigating the interplay among cellular components of neurovascular units and the effect of fluidic sheer stress in sustaining normal BBB phenotype and functions. However, an area that has received less recognition is the role of the noncellular basement membrane (BM) in modulating BBB physiology. This review describes the state-of-the-art on in vitro BBB models relevant in drug discovery research and highlights their strengths, weaknesses and the utility potential of some of these models in testing the permeability of nanocarriers as vectors for delivering therapeutics to the brain. Importantly, our review also introduces a new concept of engineering artificial BM platforms for reconstituting BBB models in vitro.

  6. Chondroitin 6-sulfate proteoglycan but not heparan sulfate proteoglycan is abnormally expressed in skin basement membrane from patients with dominant and recessive dystrophic epidermolysis bullosa

    DEFF Research Database (Denmark)

    Fine, J D; Couchman, J R


    Two distinct groups of proteoglycans, chondroitin 6-sulfate (C6-S) proteoglycan and heparan sulfate proteoglycan (HSPG), have been recently shown to reside within the lamina densa of normal human skin basement membrane (BM). To determine whether either or both antigens are normally expressed in one...... junctional EB, and all control skin specimens. We have subsequently extracted a greater than 400 kD C6-S proteoglycan from normal skin BM and have found that the core protein may also contain heparan sulfate side chains. Our findings suggest that 3B3 monoclonal antibody recognizes a hybrid proteoglycan...... in human skin, and that its absent or reduced binding in dystrophic EB skin BM may reflect either absence of associated core protein or posttranslational alterations in the proteoglycan side chains....

  7. Reciprocal interactions between Beta1-integrin and epidermal growth factor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology

    Energy Technology Data Exchange (ETDEWEB)

    Wang, F.; Weaver, V.M.; Petersen, O.W.; Larabell, C.A.; Dedhar, S.; Briand, P.; Lupu, R.; Bissell, M.J.


    Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of {beta}1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4-2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a threedimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of {beta}1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogenactivated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibodymediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant downregulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Crossmodulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and {beta}1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of {beta}1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be 'normalized' by manipulating either pathway.

  8. MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis--validation of two novel biomarker assays.

    Directory of Open Access Journals (Sweden)

    Jannie Marie Sand

    Full Text Available OBJECTIVES: Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP mediated degradation of type IV collagen, a main component of the basement membrane, will release peptide fragments (neo-epitopes into the circulation. Here we present the development of two competitive enzyme-linked immunosorbent assays (ELISAs for assessing the levels of specific fragments of type IV collagen α1 (C4M12a1 and α3 (C4M12a3 chains in serum as indicators of fibrosis. METHODS: Fragments of type IV collagen cleaved in vitro by MMP-12 were identified by mass spectrometry, and two were chosen for ELISA development due to their unique sequences. The assays were evaluated using samples from a carbon tetrachloride (CCl₄ rat model of liver fibrosis and from patients with idiopathic pulmonary fibrosis (IPF or chronic obstructive pulmonary disease (COPD. RESULTS: Two technically robust ELISAs were produced using neo-epitope specific monoclonal antibodies. Mean serum C4M12a1 levels were significantly elevated in CCl₄-treated rats compared with controls in weeks 12, 16, and 20, with a maximum increase of 102% at week 16 (p < 0.0001. Further, C4M12a1 levels correlated with the total collagen content of the liver in CCl₄-treated rats (r = 0.43, p = 0.003. Mean serum C4M12a3 levels were significantly elevated in patients with mild, moderate, and severe IPF, and COPD relative to healthy controls, with a maximum increase of 321% in COPD (p < 0.0001. CONCLUSIONS: Two assays measuring C4M12a1 and C4M12a3 enabled quantification of MMP mediated degradation of type IV collagen in serum. C4M12a1 was elevated in a pre-clinical model of liver fibrosis, and C4M12a3 was elevated in IPF and COPD patients. This suggests the use of these assays to investigate pathological remodeling of the basement membrane in different organs. However, validations in

  9. Breaches of the pial basement membrane and disappearance of the glia limitans during development underlie the cortical lamination defect in the mouse model of muscle-eye-brain disease. (United States)

    Hu, Huaiyu; Yang, Yuan; Eade, Amber; Xiong, Yufang; Qi, Yue


    Neuronal overmigration is the underlying cellular mechanism of cerebral cortical malformations in syndromes of congenital muscular dystrophies caused by defects in O-mannosyl glycosylation. Overmigration involves multiple developmental abnormalities in the brain surface basement membrane, Cajal-Retzius cells, and radial glia. We tested the hypothesis that breaches in basement membrane and the underlying glia limitans are the key initial events of the cellular pathomechanisms by carrying out a detailed developmental study with a mouse model of muscle-eye-brain disease, mice deficient in O-mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1). The pial basement membrane was normal in the knockout mouse at E11.5. It was breached during rapid cerebral cortical expansion at E13.5. Radial glial endfeet, which comprise glia limitans, grew out of the neural boundary. Neurons moved out of the neural boundary through these breaches. The overgrown radial glia and emigrated neurons disrupted the overlying pia mater. The overmigrated neurons did not participate in cortical plate (CP) development; rather they formed a diffuse cell zone (DCZ) outside the original cortical boundary. Together, the DCZ and the CP formed the knockout cerebral cortex, with disappearance of the basement membrane and the glia limitans. These results suggest that disappearance of the basement membrane and the glia limitans at the cerebral cortical surface during development underlies cortical lamination defects in congenital muscular dystrophies and a cellular mechanism of cortical malformation distinct from that of the reeler mouse, double cortex syndrome, and periventricular heterotopia.

  10. Heparanase expression,degradation of basement membrane and low degree of infiltration by immunocytes correlate with invasion and progression of human gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Zun-Jiang Xie; Ying Liu; Li-Min Jia; Ye-Chun He


    AIM: To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients.METHODS: The heparanase expression,continuity of basement,degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry,in situ hybridization and transmission electron microscopy.RESULTS: Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients.In the early stage gastric cancer tissues,basement membrane (BlVl) appeared intact,whereas in the late stage,discontinuous BM was often present.The density of $100 protein positive tumor infiltrating dendritic cells (TIDC) in the early stage gastric cancer tissues was higher than that in the late stage.The infiltrating degree of tumor infiltrating lymphocytes (TIL) in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC.There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers,but many cancer cells were found outside of the defective BM of cancer nests in the late stage.CONCLUSION: Our results suggest that strong heparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis.However,high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.

  11. [Monoclonal autoantibodies to the epithelial basement membrane cells of human skin and thymus obtained through immunization with Rickettsia prowazekii antigens]. (United States)

    Drobyshevskaia, E I; Spitsyn, S V; Nedialkov, Iu A; Shchekotikhina, Iu A; Tarasevich, I V


    As the result of immunization of BALB/c mice with the commercial preparation of typhus vaccine and R. prowazekii corpuscular antigen, in 29.2% and 40.3% of cases (respectively) the appearance of hybridomas synthesizing monoclonal antibodies (McAb) to different autologous structures (skin and thymic epithelium, cell nuclei, conjunctive tissue structures and vascular endothelium) has been revealed. The McAb under test have proved to be IgM-autoantibodies. McAb M-6, active against the basal membrane of human skin and thymic epithelium, produce quite a definite picture of disturbances in the differentiation of epithelium and can be used for the diagnosis of dyskeratosis.

  12. Crucial Role of Mesangial Cell-derived Connective Tissue Growth Factor in a Mouse Model of Anti-Glomerular Basement Membrane Glomerulonephritis (United States)

    Toda, Naohiro; Mori, Kiyoshi; Kasahara, Masato; Ishii, Akira; Koga, Kenichi; Ohno, Shoko; Mori, Keita P.; Kato, Yukiko; Osaki, Keisuke; Kuwabara, Takashige; Kojima, Katsutoshi; Taura, Daisuke; Sone, Masakatsu; Matsusaka, Taiji; Nakao, Kazuwa; Mukoyama, Masashi; Yanagita, Motoko; Yokoi, Hideki


    Connective tissue growth factor (CTGF) coordinates the signaling of growth factors and promotes fibrosis. Neonatal death of systemic CTGF knockout (KO) mice has hampered analysis of CTGF in adult renal diseases. We established 3 types of CTGF conditional KO (cKO) mice to investigate a role and source of CTGF in anti-glomerular basement membrane (GBM) glomerulonephritis. Tamoxifen-inducible systemic CTGF (Rosa-CTGF) cKO mice exhibited reduced proteinuria with ameliorated crescent formation and mesangial expansion in anti-GBM nephritis after induction. Although CTGF is expressed by podocytes at basal levels, podocyte-specific CTGF (pod-CTGF) cKO mice showed no improvement in renal injury. In contrast, PDGFRα promoter-driven CTGF (Pdgfra-CTGF) cKO mice, which predominantly lack CTGF expression by mesangial cells, exhibited reduced proteinuria with ameliorated histological changes. Glomerular macrophage accumulation, expression of Adgre1 and Ccl2, and ratio of M1/M2 macrophages were all reduced both in Rosa-CTGF cKO and Pdgfra-CTGF cKO mice, but not in pod-CTGF cKO mice. TGF-β1-stimulated Ccl2 upregulation in mesangial cells and macrophage adhesion to activated mesangial cells were decreased by reduction of CTGF. These results reveal a novel mechanism of macrophage migration into glomeruli with nephritis mediated by CTGF derived from mesangial cells, implicating the therapeutic potential of CTGF inhibition in glomerulonephritis. PMID:28191821

  13. A two-dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath.

    Directory of Open Access Journals (Sweden)

    Sara-Jane Dunn

    Full Text Available The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the context of the epithelial monolayer that lines the colonic crypt, test-tube shaped invaginations that punctuate the lining of the intestine and coordinate a regular turnover of cells to replenish the epithelial layer every few days. To investigate the consequence of genetic mutations that perturb the system dynamics and can lead to colorectal cancer, it must be possible to track the emerging tissue level changes that arise in the crypt. To that end, a theoretical crypt model with a realistic, deformable geometry is required. A new discrete crypt model is presented, which focuses on the interaction between cell- and tissue-level behaviour, while incorporating key subcellular components. The model contains a novel description of the role of the surrounding tissue and musculature, based upon experimental observations of the tissue structure of the crypt, which are also reported. A two-dimensional (2D cross-sectional geometry is considered, and the shape of the crypt is allowed to evolve and deform. Simulation results reveal how the shape of the crypt may contribute mechanically to the asymmetric division events typically associated with the stem cells at the base. The model predicts that epithelial cell migration may arise due to feedback between cell loss at the crypt collar and density-dependent cell division, an hypothesis which can be investigated in a wet lab. This work forms the basis for investigation of the deformation of the crypt structure that can occur due to proliferation of cells exhibiting mutant phenotypes, experiments that would not be possible in vivo or in vitro.

  14. Eye lens membrane junctional microdomains: a comparison between healthy and pathological cases

    Energy Technology Data Exchange (ETDEWEB)

    Buzhynskyy, Nikolay; Scheuring, Simon [Institut Curie, Equipe Inserm Avenir, UMR168-CNRS, 26 Rue d' Ulm, 75248 Paris Cedex 05 (France); Sens, Pierre [ESPCI, CNRS-UMR 7083, 75231 Paris (France); Behar-Cohen, Francine, E-mail: [UMRS Inserm 872, Universite Paris Descartes, Centre de Recherches des Cordeliers, 15 rue de l' Ecole de Medecine, 75270 Paris Cedex 06 (France)


    The eye lens is a transparent tissue constituted of tightly packed fiber cells. To maintain homeostasis and transparency of the lens, the circulation of water, ions and metabolites is required. Junctional microdomains connect the lens cells and ensure both tight cell-to-cell adhesion and intercellular flow of fluids through a microcirculation system. Here, we overview membrane morphology and tissue functional requirements of the mammalian lens. Atomic force microscopy (AFM) has opened up the possibility of visualizing the junctional microdomains at unprecedented submolecular resolution, revealing the supramolecular assembly of lens-specific aquaporin-0 (AQP0) and connexins (Cx). We compare the membrane protein assembly in healthy lenses with senile and diabetes-II cataract cases and novel data of the lens membranes from a congenital cataract. In the healthy case, AQP0s form characteristic square arrays confined by connexons. In the cases of senile and diabetes-II cataract patients, connexons were degraded, leading to malformation of AQP0 arrays and breakdown of the microcirculation system. In the congenital cataract, connexons are present, indicating probable non-membranous grounds for lens opacification. Further, we discuss the energetic aspects of the membrane organization in junctional microdomains. The AFM hence becomes a biomedical nano-imaging tool for the analysis of single-membrane protein supramolecular association in healthy and pathological membranes.

  15. Eye lens membrane junctional microdomains: a comparison between healthy and pathological cases (United States)

    Buzhynskyy, Nikolay; Sens, Pierre; Behar-Cohen, Francine; Scheuring, Simon


    The eye lens is a transparent tissue constituted of tightly packed fiber cells. To maintain homeostasis and transparency of the lens, the circulation of water, ions and metabolites is required. Junctional microdomains connect the lens cells and ensure both tight cell-to-cell adhesion and intercellular flow of fluids through a microcirculation system. Here, we overview membrane morphology and tissue functional requirements of the mammalian lens. Atomic force microscopy (AFM) has opened up the possibility of visualizing the junctional microdomains at unprecedented submolecular resolution, revealing the supramolecular assembly of lens-specific aquaporin-0 (AQP0) and connexins (Cx). We compare the membrane protein assembly in healthy lenses with senile and diabetes-II cataract cases and novel data of the lens membranes from a congenital cataract. In the healthy case, AQP0s form characteristic square arrays confined by connexons. In the cases of senile and diabetes-II cataract patients, connexons were degraded, leading to malformation of AQP0 arrays and breakdown of the microcirculation system. In the congenital cataract, connexons are present, indicating probable non-membranous grounds for lens opacification. Further, we discuss the energetic aspects of the membrane organization in junctional microdomains. The AFM hence becomes a biomedical nano-imaging tool for the analysis of single-membrane protein supramolecular association in healthy and pathological membranes.

  16. 高脂高糖家兔脑梗死模型基底膜损伤机制的探讨%Mechanism of basement membrane injury in cerebral infarction model in rabbit with hyperglycemia and hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    徐娉; 庄强


    Objective To discuss the mechanism of microvascular endothelial basement membrane injury following cerebral ischemla. Methods Twenty-four New Zealand rabbits were randomly divided into two groups (n=12): normal control group and model group. The latter were fed high-fat, high-sucrose diet, but the former was fed with normal diet. They all were made into the models of cerebral infarction. The change of Laminin (LN) in blood and the expression of LN in brain tissue were observed simultaneously. All groups received pathological examination. Results The levels of blood lipids and blood glucose of rabbit and the content of LN were significantly increased after fed with high fat and high sucrose about 1-2 times in 10 d. The plasma concentration of LN was decreased significantly after the operation of cerebral infarction (P<0.05). Pathological observation revealed that LN was mainly located in cytoplasm of microvascular matrix, and its positive reaction was yellow to brown. Conclusions Injury of the microvascular endothelial basement membrane exists in the early phase of rabbit cerebral ischemia, leading to decrease of LN in extracellular matrix. The early intervention of blood lipids and blood glucose, accompanied by the brain protection with agents and the application of inhibitors of MMPs, will be able to effectively improve the cerebral infarction.%目的 探讨脑缺血后微血管内皮细胞基底膜的损伤机制.方法 24只新西兰家兔采用随机数字表法分为非高脂高糖脑梗死模型对照组(简称空白对照组),高脂高糖脑梗死模型对照组(简称模型对照组),每组12只.空白对照组给予普通饲料,模型对照组给予高脂高糖饲料,均制作成脑梗死模型.监测造模前后血浆中层粘连蛋白(LN)的表达,并观察腩组织中LN表达情况.结果模型对照组高脂高糖模型制作后,家兔血脂血糖增高,与造模前比较差异有统计学意义(P<0.05).脑梗死模型制作后两组血浆中LN表达

  17. The clinical and pathological features of idiopathic membranous nephropathy in 246 Chinese adults

    Institute of Scientific and Technical Information of China (English)

    HUAN Hong-di; ZHANG Jing-hong; LIU Zhi-hong; LI Lei-shi; CHEN Hui-ping; ZHENG Feng


    Objective: To investigate the clinical and pathological features of idiopathic membranous nephropathy (IMN) in Chinese adults. Methods: From 1986 to 1997, 264 patients with biopsy proven membranous nephropathy were selected in this study. Clinical and pathological features were compared between patients at different ages by t test. Results: (1) Patients from 21- 40 years old were inclined to membranous nephropathy. (2) One hundred and six of the patients had heavy proteinuria at presentation. Hypertension was found in 35 patients. Renal insuffeiency occurred in 7.7% of the patients in renal biopsy. Microscopic hematuria was found in 40.2% of the patients. Seventy-four patients presented nephrotic syndrome. (3) Eight of the 57 patients had deterioration of renal function during an average 49-month follow-up. (4) Patients of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ accounted for 42.3%, 48.7%, 6.0% and 3.0% respectively. Glomeruli IgG, C3 and C1qdeposition was found in 93.2%, 98.8% and 58.3% of the patients. Conclusion: Younger patients are inclined to membranous nephropathy. The incidence of hypertension, microscopic hematuria and renal insuffcieney is similar to that of other countries, while nephrotic syndrome is uncommon.

  18. 皮肤中基底膜的结构与功能%The structure and functions of skin basement membrane

    Institute of Scientific and Technical Information of China (English)

    张丽丽; 李贤玉; 穆荣; 范春晖(综述); 北垣雅人; 高须; 惠美子(审校)


    Basement membranes (BE) are a kind of extracellular matrices in every tissue of the whole human body and play the most important role as keeping cellular functions and structures. It is the most important that BE in skin functionally connects and separates with epidermal and dermis containing of various proteins,such as type Ⅳ and Ⅶ collagen,laminins,nidogen and perlecan etc.Those interacted with themselves to form networks to support diverse bio functions in BE. And BE connects between epidermis and dermis signaling etc.It will lead the circulation smoothly among epidermis-basement membrane-dermis that healthy BE contributes diverse bio-functions,so that BE could maintain integrity and healthy of skin.Sunlight exposure may predominantly changes BE,such as sunburn, photoaging and photo-related skin cancers. On the other hand, some studies showed that various herbal extracts could protect BE well.It will be a new approach to develop functional cosmetics that how to utilize those active herbal ingredients.%基底膜是一类细胞外基质,存在于人体中所有的器官组织中,承担着重要的功能。皮肤的基底膜是表皮与真皮间重要的承接结构,主要成分有Ⅳ型和Ⅶ型胶原蛋白、层粘连蛋白、巢蛋白、串珠素等,通过它们交互形成的网状结构,构成了基底膜丰富多样的生物学功能,主要为表皮-真皮的连接功能、信号传导功能及渗透屏障功能等。健康的基底膜发挥多样生物学功能,使表皮-基底膜-真皮三者之间能够顺畅循环,保持皮肤的健康完整性。暴露于阳光下可引起基底膜的改变,可以引发多种肌肤烦恼,例如晒伤、光老化、皮肤癌等。研究发现一些植物提取物可以保护基底膜,如何运用这些活性成分对研究开发功能性化妆品可以提供更多的发展途径。

  19. Symposium: Role of the extracellular matrix in mammary development. Regulation of milk protein and basement membrane gene expression: The influence of the extracellular matrix

    Energy Technology Data Exchange (ETDEWEB)

    Aggeler, J.; Park, C.S.; Bissell, M.J.


    Synthesis and secretion of milk proteins ({alpha}-casein, {beta}-casein, {gamma}-casein, and transferrin) by cultured primary mouse mammary epithelial cells is modulated by the extracellular matrix. In cells grown on released or floating type I collagen gels, mRNA for {beta}-casein and transferrin is increased as much as 30-fold over cells grown on plastic. Induction of {beta}-casein expression depends strongly on the presence of lactogenic hormones, especially prolactin, in the culture. When cells are plated onto partially purified reconstituted basement membrane, dramatic changes in morphology and milk protein gene expression are observed. Cells cultured on the matrix for 6 to 8 d in the presence of prolactin, insulin, and hydrocortisone form hollow spheres and duct-like structures that are completely surrounded by matrix. The cells lining these spheres appear actively secretory and are oriented with their apices facing the lumen. Hybridization experiments indicate that mRNA for {beta}-casein can be increased as much as 70-fold in these cultures. Because > 90% of the cultured cells synthesize immunoreactive {beta}-casein, as compared with only 40% of cells in the late pregnant gland, the matrix appears to be able to induce protein expression in previously silent cells. Synthesis of laminin and assembly of a mammary-specific basal lamina by cells cultured on different extracellular matrices also appears to depend on the presence of lactogenic hormones. These studies provide support for the concept of dynamic reciprocity in which complex interactions between extracellular matrix and the cellular cytoskeleton contribute to the induction and maintenance of tissue-specific gene expression in the mammary gland.

  20. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli. (United States)

    Pitera, Jolanta E; Scambler, Peter J; Woolf, Adrian S


    FRAS1 is mutated in some individuals with Fraser syndrome (FS) and the encoded protein is expressed in embryonic epidermal cells, localizing in their basement membrane (BM). Syndactyly and cryptophthalmos in FS are sequelae of skin fragility but the bases for associated kidney malformations are unclear. We demonstrate that Fras1 is expressed in the branching ureteric bud (UB), and that renal agenesis occurs in homozygous Fras1 null mutant blebbed (bl) mice on a C57BL6J background. In vivo, the bl/bl bud fails to invade metanephric mesenchyme which undergoes involution, events replicated in organ culture. The expression of glial cell line-derived neurotrophic factor and growth-differentiation factor 11 was defective in bl/bl renal primordia in vivo, whereas, in culture, the addition of either growth factor restored bud invasion into the mesenchyme. Mutant primordia also showed deficient expression of Hoxd11 and Six2 transcription factors, whereas the activity of bone morphogenetic protein 4, an anti-branching molecule, was upregulated. In wild types, Fras1 was also expressed by nascent nephrons. Foetal glomerular podocytes expressed Fras1 transcripts and Fras1 immunolocalized in a glomerular BM-like pattern. On a mixed background, bl mutants, and also compound mutants for bl and my, another bleb strain, sometimes survive into adulthood. These mice have two kidneys, which contain subsets of glomeruli with perturbed nephrin, podocin, integrin alpha3 and fibronectin expression. Thus, Fras1 protein coats branching UB epithelia and is strikingly upregulated in the nephron lineage after mesenchymal/epithelial transition. Fras1 deficiency causes defective interactions between the bud and mesenchyme, correlating with disturbed expression of key nephrogenic molecules. Furthermore, Fras1 may also be required for the formation of normal glomeruli.

  1. Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus. (United States)

    Carlson Scholz, Jodi A; Garg, Rohit; Compton, Susan R; Allore, Heather G; Zeiss, Caroline J; Uchio, Edward M


    The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.

  2. Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration. (United States)

    Josephson, Matthew P; Miltner, Adam M; Lundquist, Erik A


    Nervous system development and circuit formation requires neurons to migrate from their birthplaces to specific destinations.Migrating neurons detect extracellular cues that provide guidance information. In Caenorhabditis elegans, the Q right (QR) and Q left (QL) neuroblast descendants migrate long distances in opposite directions. The Hox gene lin-39 cell autonomously promotes anterior QR descendant migration, and mab-5/Hox cell autonomously promotes posterior QL descendant migration. Here we describe a nonautonomous role of mab-5 in regulating both QR and QL descendant migrations, a role masked by redundancy with lin-39 A third Hox gene, egl-5/Abdominal-B, also likely nonautonomously regulates Q descendant migrations. In the lin-39 mab-5 egl-5 triple mutant, little if any QR and QL descendant migration occurs. In addition to well-described roles of lin-39 and mab-5 in the Q descendants, our results suggest that lin-39, mab-5, and egl-5 might also pattern the posterior region of the animal for Q descendant migration. Previous studies showed that the spon-1 gene might be a target of MAB-5 in Q descendant migration. spon-1 encodes a secreted basement membrane molecule similar to vertebrate F-spondin. Here we show that spon-1 acts nonautonomously to control Q descendant migration, and might function as a permissive rather than instructive signal for cell migration. We find that increased levels of MAB-5 in body wall muscle (BWM) can drive the spon-1 promoter adjacent to the Q cells, and loss of spon-1 suppresses mab-5 gain of function. Thus, MAB-5 might nonautonomously control Q descendant migrations by patterning the posterior region of the animal to which Q cells respond. spon-1 expression from BWMs might be part of the posterior patterning necessary for directed Q descendant migration.

  3. Targeted Expression of Stromelysin-1 in Mammary Gland Provides Evidence for a Role of Proteinases in Branching Morphogenesis and the Requirement for an Intact Basement Membrane for Tissue-specific Gene Expression

    Energy Technology Data Exchange (ETDEWEB)

    Sympson, Carolyn J; Talhouk, Rabih S; Alexander, Caroline M; Chin, Jennie R; Cliff, Shirley M; Bissell, Mina J; Werb, Zena


    The extracellular matrix (ECM) is an important regulator of the differentiated phenotype of mammary epithelial cells in culture. Despite the fact that ECM-degrading enzymes have been implicated in morphogenesis and tissue remodeling, there is little evidence for a direct role for such regulation in vivo. We generated transgenic mice that express autoactivated isoforms of the matrix metalloproteinase stromelysin-1, under the control of the whey acidic protein gene promoter, to examine the effect of inappropriate expression of this enzyme. Stromelysin-1 is implicated as the primary player in the loss of basement membrane and loss of function in the mammary gland during involution. The transgene was expressed at low levels in mammary glands of virgin female mice, leading to an unexpected phenotype: The primary ducts had supernumerary branches and showed precocious development of alveoli that expressed beta-casein at levels similar to that of an early- to mid-pregnant gland. Lactating glands showed high levels of transgene expression, with accumulation at the basement membrane, and a decrease in laminin and collagen IV, resulting in a loss of basement membrane integrity; this was accompanied by a dramatic alteration of alveolar morphology, with decreased size and shrunken lumina containing little beta-casein. During pregnancy, expression of endogenous whey acidic protein and beta-casein was reduced in transgenic glands, confirming the observed dependence of milk protein transcription of ECM in mammary epithelial cells in culture. These data provide direct evidence that stromelysin-1 activity can be morphogenic for mammary epithelial cells, inducing hyperproliferation and differentiation in virgin animals, and that its lytic activity can, indeed, disrupt membrane integrity and reduce mammary-specific function. We conclude that the balance of ECM-degrading enzymes with their inhibitors, and the associated regulation of ECM structure, is crucial for tissue-specific gene

  4. Basement membrane zone remodeling during appendageal development in human fetal skin. The absence of type VII collagen is associated with gelatinase-A (MMP2) activity. (United States)

    Karelina, T V; Bannikov, G A; Eisen, A Z


    Epithelial cell adhesion, migration, and differentiation are controlled by interactions at the basement membrane zone (BMZ). Type VII collagen is the major collagenous component of anchoring fibrils that are essential for the attachment of the epidermis to the dermis. Gelatinase A (MMP-2) is believed to be necessary for the degradation of type VII collagen. In this study we have examined the in vivo distribution of type VII collagen and gelatinase A (Gel A) in the developing human epidermis and its appendages. At 13-15 wk of gestation a marked decrease in type VII collagen immunoreactivity was seen in the BMZ surrounding invading appendageal buds; however, type VII collagen mRNA was strongly expressed in the budding epidermal keratinocytes adjacent to the BMZ. At these stages, Gel A-positive mesenchymal-like cells were found scattered throughout the stroma with numerous Gel A-containing cells in direct contact with the developing appendageal buds. In situ zymography was used to show Gel A-activity in vivo. Gel A-mediated lysis was present at the interface between the appendageal buds and the underlying BMZ. By 20-25 wk of gestational age, immunostaining for type VII collagen protein was absent from the BMZ surrounding the distal portion of invading appendageal epithelial cords of both hair follicles and sweat glands. In contrast, type VII collagen mRNA was present in the basal keratinocytes adjacent to the BMZ surrounding the distal portion of these invading appendageal epithelial cords. At these stages Gel A-positive cells were present in the stroma directly adjacent to the distal portion of developing appendageal cords that lacked type VII collagen. In situ zymography showed zones of Gel A-mediated stromal lysis at the distal portion of developing appendageal cords. Interestingly, no differences were seen in the distribution of type IV collagen in the BMZ of both budding and resting fetal epidermis. These observations suggest that the absence of type VII collagen

  5. Detection of basement membrane components on the surface of acellular porcine cornea%脱细胞猪角膜表面基底膜成分的检测

    Institute of Scientific and Technical Information of China (English)

    林旭初; 金岩; 惠延年


    BACKGROUND: The previous experiments have suggested that the acellular porcine cornea stroma (APCS) has a good compatibility and can support the growth of keratocytes and skin epithelial cellsOBJECTIVE:To detect whether the important structure for the grwth of corneal cells basement membrane canbe preserved on the surface of the APCSMETHODS: Fluorescent antibody was used to detect the basement membrane component (laminin and collagen IV) by immunohistochemistry Fluorescence microscopy was observed whether the basement membrane could be preserved on the surface oftheAPCS RESULTS AND CONCLUSION:Immunofluorescence staining showed that larnimn and collagen IV positively expressedthe APCS can preserve the natural basement membrane component of the cornea which is beneficial to the growth of comeal epithelial cells%背景:前期实验显示脱细胞猪角膜具有良好的组织相容性,可以支持角膜细胞和皮肤上皮细胞的生长.目的:检测脱细胞猪角膜是否保存了利于角膜上皮细胞生长的重要组织结构-基底膜.方法:利用荧光抗体对脱细胞猪角膜表面的基底膜成分(层粘蛋白和Ⅳ型胶原)进行免疫组织化学检测,荧光显微镜下观察脱细胞猪角膜表面是否保存了基底膜成分.结果与结论:免疫荧光染色显示脱细胞猪角膜前基质表面层粘蛋白和Ⅳ型胶原呈阳性表达,与新鲜猪角膜表面基底膜的荧光表达相同,表明脱细胞猪角膜保存了利于角膜上皮细胞生长的基底膜.

  6. Role of plasma membrane calcium ATPase 2 in spinal cord pathology

    Institute of Scientific and Technical Information of China (English)

    Amanda; Kathleen; Fakira; Stella; Elkabes


    A number of studies have indicated that plasma membrane calcium ATPases(PMCAs) are expressed in the brain and spinal cord and could play important roles not only in the maintenance of cellular calcium homeostasis but also in the survival and function of central nervous system cells under pathological conditions.The different regional and cellular distributions of the various PMCA isoforms and splice variants in the nervous system and the diverse phenotypes of PMCA knockout mice support the notion that each isoform might play a distinct role. Especially in the spinal cord,the survival of neurons and,in particular,motor neurons could be dependent on PMCA2.This is indicated by the knockdown of PMCA2 in pure spinal cord neuronal cultures that leads to cell death via a decrease in collapsing response mediator protein 1 levels.Moreover,the progressive decline in the number of motor neurons in PMCA2-null mice andheterozygous mice further supports this notion.Therefore,the reported reduction in PMCA2 mRNA and protein levels in the inflamed spinal cord of mice affected by experimental autoimmune encephalomyelitis(EAE) ,an animal model of multiple sclerosis,and after spinal cord contusion injury,suggests that changes in PMCA2 expression could be a cause of neuronal pathology and death during inflammation and injury.Glutamate excitotoxicity mediated via kainate receptors has been implicated in the neuropathology of both EAE and spinal cord injury,and has been identified as a trigger that reduces PMCA2 levels in pure spinal cord neuronal cultures through degradation of the pump by calpain without affecting PMCA2 transcript levels.It remains to be determined which other stimuli modulate PMCA2 mRNA expression in the aforementioned pathological conditions of the spinal cord.

  7. Molecular cloning of a cDNA encoding the porcine type XVII collagen noncollagenous 16 A domain and localization of the domain to the upper part of porcine skin basement membrane zone. (United States)

    Xu, Luting; Olivry, Thierry; Chan, Lawrence S


    Bullous pemphigoid is an autoimmune blistering human skin disease mediated by immunoglobulin (Ig)G autoantibodies targeting skin basement membrane component type XVII collagen, a transmembrane protein. Also designated BP180 and BPAG2, type XVII collagen is an extracellular matrix element essential for the connection between the epidermis and the underlying dermis. In addition to being a target antigen in the human disease bullous pemphigoid, type XVII collagen is also targeted by autoantibodies of canine, feline, equine and porcine patients suffering from a similar blistering skin disease. Previously, enzyme-linked immunosorbent assay and Western blot analyses have shown that autoantibodies from pigs affected with bullous pemphigoid recognize the human NC16A domain of type XVII collagen. To facilitate the development of porcine model of bullous pemphigoid, we isolated cDNA encoding the porcine type XVII collagen NC16A domain using a reverse transcription-polymerase chain reaction technique. The amino acids deduced from the NC16A cDNA showed 61% identity with the sequence of human NC16A. An antibody generated against a 20-amino acid peptide within the porcine NC16A localized the NC16A epitope to the upper part of porcine skin basement membrane zone. Our data provide further information of the porcine bullous pemphigoid target antigen and may help investigators for their further studies of this disease.

  8. Seismic basement in Poland (United States)

    Grad, Marek; Polkowski, Marcin


    The area of contact between Precambrian and Phanerozoic Europe in Poland has complicated structure of sedimentary cover and basement. The thinnest sedimentary cover in the Mazury-Belarus anteclize is only 0.3-1 km thick, increases to 7-8 km along the East European Craton margin, and 9-12 km in the Trans-European Suture Zone (TESZ). The Variscan domain is characterized by a 1- to 2-km-thick sedimentary cover, while the Carpathians are characterized by very thick sediments, up to c. 20 km. The map of the basement depth is created by combining data from geological boreholes with a set of regional seismic refraction profiles. These maps do not provide data about the basement depth in the central part of the TESZ and in the Carpathians. Therefore, the data set is supplemented by 32 models from deep seismic sounding profiles and a map of a high-resistivity (low-conductivity) layer from magnetotelluric soundings, identified as a basement. All of these data provide knowledge about the basement depth and of P-wave seismic velocities of the crystalline and consolidated type of basement for the whole area of Poland. Finally, the differentiation of the basement depth and velocity is discussed with respect to geophysical fields and the tectonic division of the area.

  9. [The enlarged diagnosis of the fatal penicillin accident. Immunehistologic demonstration of antigen-antibody complexes and of antibodies against the tubular basement membrane after administraiton of depot penicillin]. (United States)

    Dirnhofer, R; Sonnabend, W; Sigrist, T


    In a case of fatal penicillin allergy it proved possible at autopsy to demonstrate (by immunohistological examination of basal membranes of proximal renal tubuli) antigen-antibody complexes belonging to the penicillin (BPO) group and to an anti-penicilloyl antibody of the IgG type. In addition, complement C3 was detected. Antibodies against the basal membranes or renal tubuli were also demonstrated in material eluted from the kidney, although an inflammatory reaction ot the immunoligical changes had not yet been observed in light microscopy. It is undecided whether this discrepancy is due to the low dose of penicillin administered or the relatively short time lag between first injection and time of fatality. It is assumed that, pathogenetically, a reaction of the serum sickness type is probably involved. For etiological clarification the use of immunohistological methods in addition to serological procedures provides further indices for an antecedent sensitization to penicillin, because assay effectiveness does not decrease even after a lengthy postmortal time-lapse. On the other hand, tissues and serum for examination should be frozen at low temperatures immediately after autopsy.

  10. [An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis]. (United States)

    Takeda, T; Takeda, T; Naiki, Y; Yonekawa, S; Sakaguchi, M; Iwamoto, I; Tanaka, H; Hasegawa, H; Imada, A; Kanamaru, A; Hiruma, S; Maekura, S; Hashimoto, S; Yamazumi, T


    A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.

  11. Postnatal development of epididymis and ductus deferens in the rat. A correlation between the ultrastructure of the epithelium and tubule wall, and the fluorescence-microscopic distribution of actin, myosin, fibronectin, and basement membrane. (United States)

    Francavilla, S; Moscardelli, S; Properzi, G; De Matteis, M A; Scorza Barcellona, P; Natali, P G; De Martino, C


    The postnatal maturation of regions of the epididymis and intragonadal segment of the deferens duct was studied in the rat by light- and transmission electron microscopy. Maturation of the genital duct starts in the distal cauda epididymidis and ductus deferens after one week of life, and one week later, in the more cranial segments of the epididymis. Epithelial principal cells and peritubular contractile cells are structurally mature 35 days after birth. The synchronous changes of these cells indicate that the same factors control their postnatal maturation. The epithelial principal cells obtain an endocytotic apparatus and long stereocilia, whereas peritubular cells acquire contractile features. These changes are associated with a progressive increase in the immunoreaction for smooth muscle actin in both cell types. Smooth muscle myosin is detected in the apical region of the epithelial cells and the peritubular cell cytoplasm by day one of postnatal development. The differentiation of contractile cells in the wall is accompanied by progressive organization of the pericellular matrix into a continuous basement membrane. Although fibronectin is visible at birth, it is gradually removed from the tubule wall.

  12. The plasma membrane calcium pumps: focus on the role in (neuro)pathology. (United States)

    Brini, Marisa; Carafoli, Ernesto; Calì, Tito


    The plasma membrane Ca(2+) ATPase (PMCA pump) is a member of the superfamily of P-type pumps. It is organized in the plasma membrane with ten transmembrane helices and two main cytosolic loops, one of which contains the catalytic center. It also contains a long C-terminal tail that houses the binding site for calmodulin, the main regulator of the activity of the pump. The pump also contains a number of other regulators, among them acidic phospholipids, kinases, and numerous protein interactors. Separate genes code for 4 basic pump isoforms in mammals, additional isoform complexity being generated by the alternative splicing of primary transcripts. Pumps 1 and 4 are expressed ubiquitously, pumps 2 and 3 are tissue restricted, with preference for the nervous system. In essentially all cells, the pump coexists with much more powerful systems that clear Ca(2+) from the cytosol, e.g. the SERCA pump and the Na(+)/Ca(2+) exchanger. Its role in the global regulation of cellular Ca(2+) homeostasis is thus quantitatively marginal: its main function is the regulation of Ca(2+) signaling in selected sub-plasma membrane microdomains where Ca(2+) modulated interactors also reside. Malfunctions of the pump linked to genetic mutations are now described with increasing frequency, the disease phenotypes being especially severe in the nervous system where isoforms 2 and 3 predominate. The analysis of the pump defects suggests that the disease phenotypes are likely to be related to the imperfect modulation of Ca(2+) signaling in selected sub-plasma membrane microdomains, leading to the defective control of the activity of important Ca(2+) dependent interactors.

  13. Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker? (United States)

    Matteucci, Elena; Giampietro, Ottavio


    Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na(+)/H(+) exchange and HC(3) (-)/Cl(-) anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs) are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia) and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.

  14. Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

    Directory of Open Access Journals (Sweden)

    Elena Matteucci


    Full Text Available Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na+/H+ exchange and HC3 -/Cl- anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.

  15. Pathological Substratum for a Case of Fulminant Myocarditis Treated with Extracorporeal Membrane Oxygenation and Subsequent Heart Transplantation. (United States)

    Kim, In Ae; Yang, Hyun Suk; Kim, Wan Seop; Chee, Hyun Keun


    Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 23-yr-old woman with pathology-proven fulminant lymphocytic myocarditis presenting shock with elevated cardiac troponin I and ST segments in V1-2, following sustained ventricular tachycardia and a complete atrioventricular block. About 55 min of intensive cardio-pulmonary resuscitation, with extracorporeal membrane oxygenation support, bridged the patient to orthotopic heart transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls. Aggressive mechanical circulatory support may be an essential bridge for recovery or even transplantation in patients with fulminant myocarditis with shock.

  16. Still more complexity in mammalian basement membranes

    DEFF Research Database (Denmark)

    Erickson, A C; Couchman, J R


    laminins, entactin-1/nidogen-1, Type IV collagen, and proteoglycans. However, within the past few years this complexity has increased as new components are described. The entactin/nidogen (E/N) family has expanded with the recent description of a new isoform, E/N-2/osteonidogen. Agrin and Type XVIII...... collagen have been reclassified as heparan sulfate proteoglycans (HSPGs), expanding the repertoire of HSPGs in the BM. The laminin family has become more diverse as new alpha-chains have been characterized, increasing the number of laminin isoforms. Interactions between BM components are now appreciated...

  17. Presentation, clinical pathological and post-mortem findings in three related Scottish terriers with ligneous membranitis. (United States)

    Mason, S L; Fisher, C; Ressel, L; Bommer, N X; Buckley, L M; Nuttall, T


    Ligneous conjunctivitis and gingivitis were diagnosed in three related Scottish terrier dogs presented for investigation of severe conjunctivitis and respiratory signs. Hypoplasminogenaemia was confirmed in one of the three affected dogs. Supportive treatment was not effective, and the dogs died or were euthanased because of the disease. Post-mortem analysis of two of the dogs revealed multiple abnormalities including severe proliferative fibrinous lesions affecting the conjunctiva, gingiva, trachea, larynx and epicardium and multiple fibrous adhesions throughout the thoracic and abdominal cavities. One dog had internal hydrocephalus and lacked a cerebellar vermis. Ligneous membranitis was confirmed on histopathology. This is a rare condition in dogs but an important differential diagnosis for severe conjunctivitis and gingivitis.

  18. Measure Guideline: Basement Insulation Basics

    Energy Technology Data Exchange (ETDEWEB)

    Aldrich, R.; Mantha, P.; Puttagunta, S.


    This guideline is intended to describe good practices for insulating basements in new and existing homes, and is intended to be a practical resources for building contractors, designers, and also to homeowners.

  19. Helicobacter pylori outer membrane protein Q allele distribution is associated with distinct pathologies in Pakistan. (United States)

    Yakoob, Javed; Abbas, Zaigham; Khan, Rustam; Salim, Saima Azhar; Awan, Safia; Abrar, Ambar; Jafri, Wasim


    Helicobacter pylori (H. pylori) strains expressing outer membrane protein Q (HopQ) promote adherence to the gastric epithelial cell. We characterized HopQ alleles in relation to H. pylori-related disease, histology and virulence markers. Gastric biopsies were obtained at esophagogastroduodenoscopy from patients with upper gastrointestinal symptoms. H. pylori culture, histology and polymerase chain reaction (PCR) for HopQ types, cagA, cagA-promoter and vacA alleles were performed. DNA extracted was used for PCR. Sequencing of PCR products of HopQ types 1 and 2 was followed by BLAST query. We examined 241 H. pylori isolates. HopQ type 1 was positive in 70 (29%) isolates, type 2 in 60 (25%) isolates, while both type 1 and type 2 in 111 (46%) H. pylori isolates, respectively. Nonulcer dyspepsia (NUD) was associated with HopQ type 2 in 48 (41%) isolates, while gastric carcinoma (GC) in 37 (53%) (P<0.001) with type 1 isolates. Gastric ulcers (GU) were 39 (46%) (P<0.001) in H. pylori infection with multiple HopQ alleles compared to 6 (23%) in HopQ type 1. Multivariate analysis demonstrated that multiple HopQ alleles were associated with GU OR 2.9 (1.07-7.8) (P=0.03). HopQ type 1 was associated with cagA 58 (84%) (P<0.001) and cagA-promoter 58 (83%) (P<0.001) compared to 14 (23%) and 17 (28%) respectively, in type 2. VacAs1a was associated with HopQ type 1 in 59 (84%) isolates compared to HopQ type 2 in 35 (58%) (P=0.002) isolates. VacAm1 was associated with HopQ type 1 in 53 (76%) isolates compared to HopQ type 2 in 32 (53%) (P=0.004) isolates. H. pylori infection with multiple HopQ alleles was predominant. H. pylori infection with single HopQ type 1 was associated with GC in the presence of other H. pylori virulence markers.

  20. Viruses in the Oceanic Basement (United States)

    Jungbluth, Sean P.; Lin, Huei-Ting; Hsieh, Chih-Chiang; Miranda, Jaclyn A.; Schvarcz, Christopher R.; Rappé, Michael S.


    ABSTRACT Microbial life has been detected well into the igneous crust of the seafloor (i.e., the oceanic basement), but there have been no reports confirming the presence of viruses in this habitat. To detect and characterize an ocean basement virome, geothermally heated fluid samples (ca. 60 to 65°C) were collected from 117 to 292 m deep into the ocean basement using seafloor observatories installed in two boreholes (Integrated Ocean Drilling Program [IODP] U1362A and U1362B) drilled in the eastern sediment-covered flank of the Juan de Fuca Ridge. Concentrations of virus-like particles in the fluid samples were on the order of 0.2 × 105 to 2 × 105 ml−1 (n = 8), higher than prokaryote-like cells in the same samples by a factor of 9 on average (range, 1.5 to 27). Electron microscopy revealed diverse viral morphotypes similar to those of viruses known to infect bacteria and thermophilic archaea. An analysis of virus-like sequences in basement microbial metagenomes suggests that those from archaeon-infecting viruses were the most common (63 to 80%). Complete genomes of a putative archaeon-infecting virus and a prophage within an archaeal scaffold were identified among the assembled sequences, and sequence analysis suggests that they represent lineages divergent from known thermophilic viruses. Of the clustered regularly interspaced short palindromic repeat (CRISPR)-containing scaffolds in the metagenomes for which a taxonomy could be inferred (163 out of 737), 51 to 55% appeared to be archaeal and 45 to 49% appeared to be bacterial. These results imply that the warmed, highly altered fluids in deeply buried ocean basement harbor a distinct assemblage of novel viruses, including many that infect archaea, and that these viruses are active participants in the ecology of the basement microbiome. PMID:28270584

  1. Screening and identification of neutralizated single-chain antibody of anti-glomerular basement membrane antibody%中和抗肾小球基底膜抗体的单链抗体的筛选与鉴定

    Institute of Scientific and Technical Information of China (English)

    肖静; 刘章锁; 王沛; 黄留玉; 宋宏彬; 赵明辉


    Objective To screen a human single-chain variable fragments(scFv)against antiGBM antibody.Methods Using phage display technique,the phage antibody library was panned by antiglomerular basement membrane(GBM)antibody which was coated in a micro-titer plate,one clone was found to have high affinity to anti-GBM antibody.The DNA sequence of the positive clone was determined.Results Along with the increase of rounds anti-GBM antibody specific phage antibody was highly enriched and screening efficiency was increased 137 folds than the firest round.ELISA and competition inhibition assay showed that the scFv had a specific combination character with anti-GBM antibody.DNA sequencing confirmed that the whole gene of scFv was 750 bp,and in accordance with humanized single-chain variable region antibody sequence structure.Conclusion The results suggested that the scFv fragment to anti-GBM antibody could be successfully selected by recombinant phage antibody technique,which will laid an experimental foundation for further research of the therapy of Goodpasture syndrome.%目的 制备人抗肾小球基底膜(GBM)抗体的特异性人源化单链可变区抗体.方法 采用噬菌体表面展示技术,获得一个与人抗GBM抗体结合活性较强的单链可变区抗体片段的阳性克隆,并对该克隆进行DNA序列测定分析.结果 对噬菌体单链可变区抗体库经过3轮筛选后,与第1轮相比富集了137倍.噬菌体抗体与人抗GBM抗体的结合活性其中有35株克隆ELISA的吸光度较高.对这些噬菌体抗体进行交叉反应后,确定其中有10株交叉反应较弱.确定1株(C31)阳性克隆提取质粒,进行DNA序列测定,大小为750 bp,并符合人源化单链可变区抗体的序列结构.结论 应用噬菌体展示技术成功获得人-抗GBM抗体的单链可变区抗体基因,为临床上治疗Goodpasture综合征奠定实验基础.

  2. Relationship between the changes in ischemia/reperfusion cerebro-microvessel basement membrane injury and gelatinase system in senile rat%老龄大鼠脑缺血/再灌注致脑微血管基底膜损伤的变化及与明胶酶系的关系

    Institute of Scientific and Technical Information of China (English)

    李建生; 刘轲; 刘敬霞; 王明航; 赵跃武; 刘正国


    Objective To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion(I/R)in aged rats.Methods Cerebral I/R injury model was reproduced by intraluminal silk ligature thrombosis of the middle cerebral artery occlusion (MCAO).Rats were divided randomly into sham control and I/R groups in young rats Cischemia 3 hours (13 h)and reperfusion 6 hours(I/R 6 h),12 hours(1/R 12 h),24 hours(I/R 24 h),3 days(1/R 3 d),6 days(I/R 6 d)],and sham control group and I/R group in aged rats(1 3 h and I/R 6 h,I/R 12 h,I/R 24 h,1/R 3 d,1/R 6 d).The change in cerebro-cortex microvessel basement membrane structure,basement membrane type Ⅳ collagen(Col Ⅳ)and laminin(LN)contents,matrix metalloproteinases(MMPs)and tissue inhibitor of metalloproteinases(TIMPs)expression in every group were determined with immunohis tochemical method and zymogram analysis.Results With the inerease in age,Col Ⅳ and LN contents of the microvessel basement membrane were increased,and MMP-2 and MMP-9 expressions were stronger.With prolongation of I/R.the degradation of microvessel basement membrane components(Col Ⅳ and LN)was positively correlated with the duration of cerebral I/R.MMP-2 expression was increased gradually,and MMP-9 and TIMP-1 expression increased at the beginning and decreased subsequently.Col Ⅳ(I 3 h,I/R 6 h,I/R 12 h),LN(1 3 h,I/R 6-24 h),MMP-2(I 3 h,1/R 6 h-6 d)and MMP-9(1 3 h,I/R 6-24 h)expression level in aged rats with I/R injury were higher,and TIMP-1(I/R 24 h)expression was lower than those in young rats(P<0.05 or P<0.01).In addition,changes in MMP-2 and MMP-9 contents as determined by zymogram analysis method coincided with their immunoexpression.Conclusion With the increase of age,alteration in membrane components of eerebro-microvessel basement membrane in rats is related with MMPs and TlMP.Cerebro-mierovesseI basement membrane injury is more serious in aged rats than that of young rats.Changes in

  3. Study on Effect Difference between Guizhi Decoction and Huanglianjiedu Decoction on Immuno - inflammatory Factors and Myocardial Basement Membrane in Spontaneous Diabetic Rats%桂枝汤和黄连解毒汤对 GK 大鼠心肌炎症因子及基膜影响的差异研究

    Institute of Scientific and Technical Information of China (English)

    姜萍; 戴玲玲; 王雪; 李晓


    目的:观察桂枝汤及黄连解毒汤对自发性糖尿病大鼠(GK 大鼠)心肌基膜厚度、心肌核因子-κB(NF -κB)、Ⅳ型胶原表达的作用,探讨有关炎症损伤的机制。方法以 Wistar 大鼠10只作为正常对照组,40只 GK 大鼠随机分为 GK 对照组、二甲双胍组、黄连解毒汤组、桂枝汤组,分别以相应药物灌胃给药12周,检测各组血糖、NF -κB、Ⅳ型胶原阳性表达程度及基膜厚度。结果 GK大鼠血糖升高,NF -κB 阳性表达增强,Ⅳ型胶原蛋白表达增强,基底膜厚度增加。二甲双胍、黄连解毒汤均可降低 GK 大鼠血糖(P ﹤0.01)。黄连解毒汤和桂枝汤均能降低 NF -κB 及Ⅳ型胶原蛋白表达、降低基底膜厚度与 GK 大鼠对照组比较差异有统计学意义(P ﹤0.01,P ﹤0.05)。在抑制 NF -κB阳性表达方面,桂枝汤和黄连解毒汤疗效无统计学意义。在抑制Ⅳ型胶原蛋白表达、降低基底膜厚度方面,桂枝汤作用强于黄连解毒汤(P ﹤0.01,P ﹤0.05)。结论桂枝汤和黄连解毒汤均可以抑制 NF-κB 阳性表达,抑制Ⅳ型胶原蛋白表达,降低基膜厚度,且桂枝汤优于黄连解毒汤,显示了其调和营卫治法的独特作用。%Objective To observe the effect of Guizhi decoction and Huanglianjiedu decoction on the thickness of myocardial basement membrane and the expression of NF - κB and type IV collagen,and to explore the mechanism of inflammatory injury in Spontaneous diabetic rats(GK rats). Methods Ten Wister rats were included in the control group,while forty GK rats were randomly divided into GK control group,met-formin group,Huanglianjiedu decoction group and Guizhi decoction group. Each group was respectively ad-ministrated the corresponding dose of drugs for 12 weeks. Then blood glucose,the degree of positive expres-sion of myocardial NF - κB and type IV collagen and the changes of basement membrane thickness were de

  4. Role of laminins in physiological and pathological angiogenesis. (United States)

    Simon-Assmann, Patricia; Orend, Gertraud; Mammadova-Bach, Elmina; Spenlé, Caroline; Lefebvre, Olivier


    The interaction of endothelial cells and pericytes with their microenvironment, in particular with the basement membrane, plays a crucial role during vasculogenesis and angiogenesis. In this review, we focus on laminins, a major family of extracellular matrix molecules present in basement membranes. Laminins interact with cell surface receptors to trigger intracellular signalling that shapes cell behaviour. Each laminin exerts a distinct effect on endothelial cells and pericytes which largely depends on the adhesion receptor profile expressed on the cell surface. Moreover, proteolytic cleavage of laminins may affect their role in angiogenesis. We report in vitro and in vivo data on laminin-111, -411, -511 and -332 and their associated signalling that regulates cell behaviour and angiogenesis under normal and pathological conditions. We also discuss how tissue-specific deletion of laminin genes affects the behaviour of endothelial cells and pericytes and thus angiogenesis. Finally, we examine how coculture systems with defined laminin expression contribute to our understanding of the roles of laminins in normal and pathological vasculogenesis and angiogenesis.

  5. Membraner

    DEFF Research Database (Denmark)

    Bach, Finn


    Notatet giver en kort introduktion til den statiske virkemåde af membraner og membrankonstruktioner......Notatet giver en kort introduktion til den statiske virkemåde af membraner og membrankonstruktioner...

  6. Extracellular Membrane Vesicles as Vehicles for Brain Cell-to-Cell Interactions in Physiological as well as Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Gabriella Schiera


    Full Text Available Extracellular vesicles are involved in a great variety of physiological events occurring in the nervous system, such as cross talk among neurons and glial cells in synapse development and function, integrated neuronal plasticity, neuronal-glial metabolic exchanges, and synthesis and dynamic renewal of myelin. Many of these EV-mediated processes depend on the exchange of proteins, mRNAs, and noncoding RNAs, including miRNAs, which occurs among glial and neuronal cells. In addition, production and exchange of EVs can be modified under pathological conditions, such as brain cancer and neurodegeneration. Like other cancer cells, brain tumours can use EVs to secrete factors, which allow escaping from immune surveillance, and to transfer molecules into the surrounding cells, thus transforming their phenotype. Moreover, EVs can function as a way to discard material dangerous to cancer cells, such as differentiation-inducing proteins, and even drugs. Intriguingly, EVs seem to be also involved in spreading through the brain of aggregated proteins, such as prions and aggregated tau protein. Finally, EVs can carry useful biomarkers for the early diagnosis of diseases. Herein we summarize possible roles of EVs in brain physiological functions and discuss their involvement in the horizontal spreading, from cell to cell, of both cancer and neurodegenerative pathologies.

  7. Protection against Chlamydia trachomatis infection and upper genital tract pathological changes by vaccine-promoted neutralizing antibodies directed to the VD4 of the major outer membrane protein

    DEFF Research Database (Denmark)

    Olsen, Anja W.; Follmann, Frank; Erneholm, Karin Susanne;


    The VD4 region from the Chlamydia trachomatis major outer membrane protein contains important neutralizing B-cell epitopes of relevance for antibody-mediated protection against genital tract infection. We developed a multivalent vaccine construct based on VD4s and their surrounding constant...... segments from serovars D, E, and F. Adjuvanted with cationic liposomes, this construct promoted strong immune responses to serovar-specific epitopes, the conserved LNPTIAG epitope and neutralized serovars D, E, and F. Vaccinated mice were protected against challenge, with protection defined as reduced...... bacterial numbers in vagina and prevention of pathological changes in the upper genital tract. Adoptive transfer of serumand T-cell depletion experiments demonstrated a dominant role for antibodies and CD4+ T cells in the protective immune response. Integrating a multivalent VD4 construct into the sequence...

  8. Oxidant Status and Lipid Composition of Erythrocyte Membranes in Patients with Type 2 Diabetes, Chronic Liver Damage, and a Combination of Both Pathologies

    Directory of Open Access Journals (Sweden)

    Rolando Hernández-Muñoz


    Full Text Available There is an important set of cirrhotic and diabetic patients that present both diseases. However, information about metabolic and cellular blood markers that are altered, in conjunction or distinctively, in the 3 pathological conditions is scarce. The aim of this project was to evaluate several indicators of prooxidant reactions and the membrane composition of blood samples (serum and red blood cells (RBCs from patients clinically classified as diabetic (n=60, cirrhotic (n=70, and diabetic with liver cirrhosis (n=25 as compared to samples from a similar population of healthy individuals (n=60. The results showed that levels of TBARS, nitrites, cysteine, and conjugated dienes in the RBC of cirrhotic patients were significantly increased. However, the coincidence of diabetes and cirrhosis partially reduced the alterations promoted by the cirrhotic condition. The amount of total phospholipids and cholesterol was greatly enhanced in the patients with both pathologies (between 60 and 200% according to the type of phospholipid but not in the patients with only one disease. Overall, the data indicate that the cooccurrence of diabetes and cirrhosis elicits a physiopathological equilibrium that is different from the alterations typical of each individual malady.

  9. Morphision: A method for subjective evaluation of metamorphopsia in patients with unilateral macular pathology (i.e., full thickness macular hole and epiretinal membrane

    Directory of Open Access Journals (Sweden)

    Marta Ugarte


    Full Text Available Background: Lack of clinical tests to quantify spatial components of distortion in patients with full thickness macular holes (FTMH and epiretinal membranes (ERM. Aim: To develop a test for subjective evaluation of visual distortion in the central visual field around fixation in patients with unilateral FTMH or ERM. Settings and Design: Prospective case-control study carried out at tertiary referral center. Materials and Methods: Twenty-five patients with unilateral macular disease (13 macular epiretinal membranes, 12 full-thickness macular holes, and nine controls (without ocular pathology underwent ophthalmological examination with logMAR ETDRS visual acuity, near vision and contrast sensitivity assessed. Macular optical coherence tomography and metamorphopsia assessment using Morphision test was also carried out. This test consists of a set of modified Amsler charts for detection, identification, and subjective quantification of visual distortion in the central visual field around fixation. Morphision test content and construct validity, and reliability (test-retest method were evaluated. Sixteen patients completed an unstructured survey on test performance and preference. Results: Every patient with unilateral FTMH or ERM identified a particular chart using Morphision test (content validity. None of the normal subjects without symptoms of metamorphopsia identified any distortion (construct validity. Test-retest showed a 100% consistency for frequency and 67% for amplitude. The mean amplitude difference between measurements was 0.02 degrees (SD = 0.038. The coefficient of repeatability was 0.075. There was a correlation between Morphision amplitude score and visual acuity and contrast sensitivity, individually. Conclusions: Morphision test allowed detection and subjective quantification of metamorphopsia in the clinical setting in our patients with unilateral macular epiretinal membranes and full thickness macular holes.

  10. Possible Roles of Proinflammatory and Chemoattractive Cytokines Produced by Human Fetal Membrane Cells in the Pathology of Adverse Pregnancy Outcomes Associated with Influenza Virus Infection

    Directory of Open Access Journals (Sweden)

    Noboru Uchide


    Full Text Available Pregnant women are at an increased risk of influenza-associated adverse outcomes, such as premature delivery, based on data from the latest pandemic with a novel influenza A (H1N1 virus in 2009-2010. It has been suggested that the transplacental transmission of influenza viruses is rarely detected in humans. A series of our study has demonstrated that influenza virus infection induced apoptosis in primary cultured human fetal membrane chorion cells, from which a factor with monocyte differentiation-inducing (MDI activity was secreted. Proinflammatory cytokines, such as interleukin (IL-6, tumor necrosis factor (TNF-α, and interferon (IFN-β, were identified as a member of the MDI factor. Influenza virus infection induced the mRNA expression of not only the proinflammatory cytokines but also chemoattractive cytokines, such as monocyte chemoattractant protein (MCP-1, regulated on activation, normal T-cell expressed and secreted (RANTES, macrophage inflammatory protein (MIP-1β, IL-8, growth-regulated oncogene (GRO-α, GRO-β, epithelial cell-derived neutrophil-activating protein (ENA-78, and interferon inducible protein (IP-10 in cultured chorion cells. These cytokines are postulated to associate with human parturition. This paper, therefore, reviews (1 lessons from pandemic H1N1 2009 in pregnancy, (2 production of proinflammatory and chemoattractive cytokines by human fetal membranes and their functions in gestational tissues, and (3 possible roles of cytokines produced by human fetal membranes in the pathology of adverse pregnancy outcomes associated with influenza virus infection.


    Institute of Scientific and Technical Information of China (English)


    Objective To investigate the clinical pathological feature and diagnostic criteria of tongue amyloidosis (AL).Methods During 1992 to 2005, 25 patients pathologically diagnosed as tongue AL in our hospital were reviewed retrospectively, and all of them had no enlarged tongue. Haematoxylin and eosin (HE) and immunohistochemical staining were used to detect the amyloid deposition on the tongue.Results Totally 84 % (21/25) patients had symptoms of xerostomia and taste-blindness, 44 % (11/25) patients complained of activity limitation of tongue. Macroscopic observation showed mucosa pallescence, punctuate hemorrhage, red grain particles, and ulcers on the tongue. HE staining indicated amyloid depositions in basement membrane,muscle cell, vessel wall, and nerve fiber. Immunohistochemical study demonstrated kappa light-chain deposition in 64%(16/25) cases, and lambda light-chain deposition in 36 % (9/25) cases. They presented in vessel wall, nerve fiber, and muscle cells.Conclusion The biopsy is an important means for the diagnosis of early tongue AL, and the wide variety of amyloid light chain is helpful to differential diagnosis.

  12. Heterogeneous Pathology of Melasma and Its Clinical Implications

    Directory of Open Access Journals (Sweden)

    Soon-Hyo Kwon


    Full Text Available Melasma is a commonly acquired hypermelanosis that affects sun-exposed areas of the skin, with frequent facial involvement. Its histologic manifestations are evident in the epidermis, extracellular matrix, and dermis. In addition to epidermal pigmentation, pathologic findings of melasma include extracellular matrix abnormality, especially solar elastosis. The disrupted basement membrane has been described in melasma with variable incidences. In the dermis, an increase in vascularity and an increase in the number of mast cells were observed, indicating that dermal factors have critical roles in the pathogenesis of melasma, despite the fact that melasma is characterized by epidermal hyperpigmentation. This review discusses such histologic characteristics of melasma, with consideration to their implications for melasma treatment.

  13. Heterogeneous Pathology of Melasma and Its Clinical Implications. (United States)

    Kwon, Soon-Hyo; Hwang, Young-Ji; Lee, Soo-Keun; Park, Kyoung-Chan


    Melasma is a commonly acquired hypermelanosis that affects sun-exposed areas of the skin, with frequent facial involvement. Its histologic manifestations are evident in the epidermis, extracellular matrix, and dermis. In addition to epidermal pigmentation, pathologic findings of melasma include extracellular matrix abnormality, especially solar elastosis. The disrupted basement membrane has been described in melasma with variable incidences. In the dermis, an increase in vascularity and an increase in the number of mast cells were observed, indicating that dermal factors have critical roles in the pathogenesis of melasma, despite the fact that melasma is characterized by epidermal hyperpigmentation. This review discusses such histologic characteristics of melasma, with consideration to their implications for melasma treatment.

  14. Amyotrophic lateral sclerosis mutant vesicle-associated membrane protein-associated protein-B transgenic mice develop TAR-DNA-binding protein-43 pathology.

    LENUS (Irish Health Repository)

    Tudor, E L


    Cytoplasmic ubiquitin-positive inclusions containing TAR-DNA-binding protein-43 (TDP-43) within motor neurons are the hallmark pathology of sporadic amyotrophic lateral sclerosis (ALS). TDP-43 is a nuclear protein and the mechanisms by which it becomes mislocalized and aggregated in ALS are not properly understood. A mutation in the vesicle-associated membrane protein-associated protein-B (VAPB) involving a proline to serine substitution at position 56 (VAPBP56S) is the cause of familial ALS type-8. To gain insight into the molecular mechanisms by which VAPBP56S induces disease, we created transgenic mice that express either wild-type VAPB (VAPBwt) or VAPBP56S in the nervous system. Analyses of both sets of mice revealed no overt motor phenotype nor alterations in survival. However, VAPBP56S but not VAPBwt transgenic mice develop cytoplasmic TDP-43 accumulations within spinal cord motor neurons that were first detected at 18 months of age. Our results suggest a link between abnormal VAPBP56S function and TDP-43 mislocalization.

  15. Pathology of diabetic myocardiac microangiopathy

    Institute of Scientific and Technical Information of China (English)

    Yiqun Yao; Yanmei Chen; Guang Liu; Zhiyong Pei


    Objective To investigate the cause of high cardiovascular lethality in patients with diabetics mellitus. Methods Sections from autopsied coronary arteries and myocardium of dead patients with non-insulin-dependent diabetics mellitus and 12 dead control subjects were used for histomorphometric studies. Results The coronary atherosclerotic lesion in diabetics patients was not different in severity from those in controls. Nor was there difference in number of myofibers or diameters of myocardic fibers and capillaries.But the capillary density and the ratio of capillary number to myocardic fiber number in diabetics group were significeantly reduced compared with control group(P<0.0 l),and the capillary basement membrane in the former was significantly thicker than in the latter(P<0.01).Conclision The decrease in number of capillaries and the thickening of basement membrane enhance myocardiac vulnerability to further ischemia and hypoxia,which may undelie high lethality of myocardiopathy in diabetic patients.

  16. Determinants of pathologic mineralization. (United States)

    Kirsch, Thorsten


    Physiologic mineralization is necessary for the formation of skeletal tissues and for their appropriate functions during adulthood. Mineralization has to be controlled and restricted to specific regions. If the mineralization process occurs in regions that normally do not mineralize, there can be severe consequences (pathologic or ectopic mineralization). Recent findings have indicated that physiologic and pathologic mineralization events are initiated by matrix vesicles, membrane-enclosed particles released from the plasma membranes of mineralization-competent cells. The understanding of how these vesicles are released from the plasma membrane and initiate the mineralization process may provide novel therapeutic strategies to prevent pathologic mineralization. In addition, other regulators (activators and inhibitors) of physiologic mineralization have been identified and characterized, and there is evidence that the same factors also contribute to the regulation of pathologic mineralization. Finally, programmed cell death (apoptosis) may be a contributor to physiologic mineralization and if occurring after tissue injury may induce pathologic mineralization and mineralization-related differentiation events in the injured and surrounding areas. This review describes how the understanding of mechanisms and factors regulating physiologic mineralization can be used to develop new therapeutic strategies to prevent pathologic or ectopic mineralization events.

  17. Clinical and genetic features of X-linked Alport syndrome in men positive for the collagen Ⅳ a5 chain in epidermal basement membrane%皮肤基底膜Ⅳ型胶原α5链染色正常的男性X连锁Alport综合征基因型和表型分析

    Institute of Scientific and Technical Information of China (English)

    张琰琴; 丁洁; 王芳; 张宏文; 肖慧捷; 姚勇; 钟旭辉; 管娜; 刘晓宇


    目的 分析皮肤基底膜Ⅳ型胶原α5[α5(Ⅳ)]链染色正常的男性x连锁Alport综合征(XLAS)的基因突变和临床特点.方法 回顾性分析1998年1月至2014年12月北京大学第一医院儿科诊断为Alport综合征的725个家系,其中男性XLAS患者450例,通过入选标准:(1)有皮肤基底膜Ⅳ型胶原α5链染色检查,(2)存在COI4A5基因突变,筛选出α5(Ⅳ)染色正常及α5(Ⅳ)染色阴性的男性XLAS患者,比较、分析两组基因突变和临床特点的差异.组间比较采用Mann-Whitney检验或x2检验.结果 共140例男性XLAS患者既进行了皮肤基底膜Ⅳ型胶原α5链染色检查又检测到了COI4A5基因突变.其中α5(Ⅳ)染色正常组18例,α5(Ⅳ)染色阴性组122例.两组患者就诊中位数年龄分别为11.0、7.2岁(Z=-1.839,P=0.066),就诊时24h尿蛋白定量中位数分别是1.50、0.57 g/d(Z=-1.212,P=0.226),合并听力减退28%、53%(x2=3.619,P=0.067),进展至终末期肾脏病(ESRD)的分别为4、12例(x2=2.377,P=0.128),ESRD发生的中位数年龄分别是31.0、16.6岁(Z=-2.554,P=0.011),COL4A5基因错义突变分别为12例(67%)、63例(52%)(x2=1.424,P=0.313).结论 皮肤基底膜α5(Ⅳ)染色正常的男性XLAS患者与α5(Ⅳ)染色阴性的男性XLAS患者在尿蛋白定量、听力减退发生率、COL4A5基因型差别不明显,但α5(Ⅳ)染色正常组患者发生ESRD的年龄明显较晚.%Objective To analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5 (Ⅳ) chain in epidermal basement membrane.Method This was a retrospective study.Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS.Patients who met both of the following two criteria were included in this study.(1) Patients underwent α5 (Ⅳ) chain staining in the epidermal basement membrane.(2

  18. Attachment of cells to basement membrane collagen type IV



    Of ten different cell lines examined, three showed distinct attachment and spreading on collagen IV substrates, and neither attachment nor spreading was enhanced by adding soluble laminin or fibronectin. This reaction was not inhibited by cycloheximide or antibodies to laminin, indicating a direct attachment to collagen IV without the need of mediator proteins. Cell-binding sites were localized to the major triple-helical domain of collagen IV and required an intact triple helical conformatio...

  19. Mouse endometrial stromal cells produce basement-membrane components

    DEFF Research Database (Denmark)

    Wewer, U M; Damjanov, A; Weiss, J;


    During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations. The dec...

  20. Collagen IV in normal skin and in pathological processes

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu-Velez


    Full Text Available Context: Type IV collagen is a type of collagen found primarily in the skin within the basement membrane zone. The type IV collagen C4 domain at the C-terminus is not removed in post-translational processing, and the fibers are thus link head-to-head, rather than in a parallel fashion. Also, type IV collagen lacks a glycine in every third amino-acid residue necessary for the tight collagen helix. Thus, the overall collagen-IV conformation is structurally more pliable and kinked, relative to other collagen subtypes. These structural features allow collagen IV to form sheets, which is the primary structural form found in the cutaneous basal lamina. There are six human genes associated with collagen IV, specifically COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6. The aim of this review is to highlight the significance of this protein in normal skin, and in selected diseases. Results: The alpha 3 protein constituent of type IV collagen is thought to be the antigen implicated in Goodpasture′s syndrome, wherein the immune system attacks the basement membranes of the renal glomeruli and pulmonary alveoli. In addition, mutations to the genes coding for type IV collagen lead to the Alport syndrome. Furthermore, autoantibodies directed against denatured human type IV collagen have been described in rheumatoid arthritis, scleroderma, and SLE. Structural studies of collagen IV have been utilized to differentiate between subepidermal blistering diseases, including bullous pemphigoid, acquired epidermolysis bullosa, anti-epiligrin cicatricial pemphigoid, and bullous lupus erythematosus. Collagen IV is also of importance in wound healing and in embryogenesis. Conclusions: Pathological studies have demonstrated that minor structural differences in collagen IV can lead to distinct, clinically different diseases.

  1. Myoepithelial cells in pathology. (United States)

    Balachander, N; Masthan, K M K; Babu, N Aravindha; Anbazhagan, V


    Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically myoepithelial cells are thin and spindle-shaped and ultrastructurally they possess a number of Cytoplasmic processes that extend between and over the acinar and ductal-lining cells, and they show features of both smooth muscle and epithelium. They play a vital role during expulsion of saliva and regulates the electrolytic exchange. They also perform as tumor suppressors and are considered to play a very important role in differentiation of various salivary gland tumors and help in the diagnosis of tumors. Neoplastic myoepithelial cells in both benign and malignant tumors can take numerous forms including epithelioid, plasmacytoid, spindle and clear cell variant, and this variability largely accounts for difficulties in histopathological diagnosis.

  2. Myoepithelial cells in pathology

    Directory of Open Access Journals (Sweden)

    N Balachander


    Full Text Available Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically myoepithelial cells are thin and spindle-shaped and ultrastructurally they possess a number of Cytoplasmic processes that extend between and over the acinar and ductal-lining cells, and they show features of both smooth muscle and epithelium. They play a vital role during expulsion of saliva and regulates the electrolytic exchange. They also perform as tumor suppressors and are considered to play a very important role in differentiation of various salivary gland tumors and help in the diagnosis of tumors. Neoplastic myoepithelial cells in both benign and malignant tumors can take numerous forms including epithelioid, plasmacytoid, spindle and clear cell variant, and this variability largely accounts for difficulties in histopathological diagnosis.

  3. Osler's pathology. (United States)

    Pai, S A


    Sir William Osler, one of the giants of clinical medicine, had his initial training as a pathologist. He was one of the physicians responsible for the impact that autopsies have had on medicine. He also contributed to the development of laboratory medicine. Osler made significant discoveries in anatomic pathology and hematology. His expertise was restricted not just to human pathology, but also to veterinary pathology. His mentors played a fundamental role in his achievements in academics.

  4. [Pathological jealousy]. (United States)

    Zacher, A


    Pathological jealousy can make life unbearable for all concerned. The proximity of this condition to obsessive-compulsive phenomena has given rise to the notion that it might respond to substances of proven value in the treatment of obsessive-compulsive disorders. This case history exemplifies the successful treatment of pathological jealousy with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The substance not only proved to be a successful antidepressant, but also effectively mitigated the anguish of the patient's pathological jealousy. On the basis of these findings, fluoxetine--as also other SSRIs--should always be considered as a possible effective pharmacological strategy for the treatment of pathological jealousy.

  5. Oral pathology. (United States)

    Niemiec, Brook A


    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  6. Protection against Chlamydia trachomatis infection and upper genital tract pathological changes by vaccine-promoted neutralizing antibodies directed to the VD4 of the major outer membrane protein

    DEFF Research Database (Denmark)

    Olsen, Anja W.; Follmann, Frank; Erneholm, Karin Susanne


    The VD4 region from the Chlamydia trachomatis major outer membrane protein contains important neutralizing B-cell epitopes of relevance for antibody-mediated protection against genital tract infection. We developed a multivalent vaccine construct based on VD4s and their surrounding constant segme...... of the major outer membrane protein resulted in a protective and broadly neutralizing vaccine. Our findings emphasize the important role of antibodies in protection against Chlamydia trachomatis.......The VD4 region from the Chlamydia trachomatis major outer membrane protein contains important neutralizing B-cell epitopes of relevance for antibody-mediated protection against genital tract infection. We developed a multivalent vaccine construct based on VD4s and their surrounding constant...... segments from serovars D, E, and F. Adjuvanted with cationic liposomes, this construct promoted strong immune responses to serovar-specific epitopes, the conserved LNPTIAG epitope and neutralized serovars D, E, and F. Vaccinated mice were protected against challenge, with protection defined as reduced...

  7. Digital pathology

    CERN Document Server

    Sucaet, Yves


    Digital pathology has experienced exponential growth, in terms of its technology and applications, since its inception just over a decade ago. Though it has yet to be approved for primary diagnostics, its values as a teaching tool, facilitator of second opinions and quality assurance reviews and research are becoming, if not already, undeniable. It also offers the hope of providing pathology consultant and educational services to under-served areas, including regions of the world that could not possibly sustain this level of services otherwise. And this is just the beginning, as its adoption b

  8. A rapid method for determining arachidonic:eicosapentaenoic acid ratios in whole blood lipids: correlation with erythrocyte membrane ratios and validation in a large Italian population of various ages and pathologies

    Directory of Open Access Journals (Sweden)

    Corsetto Paola


    Full Text Available Abstract Background Omega-3 and -6 polyunsaturated fatty acids (LCPUFA, are important for good health conditions. They are present in membrane phospholipids. The ratio of total n-6:n-3 LCPUFA and arachidonic acid:eicosapentaenoic acid (AA and EPA, should not exceed 5:1. Increased intake of n-6 and decreased consumption of n-3 has resulted in much higher, ca 10/15:1 ratio in RBC fatty acids with the possible appearance of a pathological "scenario". The determination of RBC phospholipid LCPUFA contents and ratios is the method of choice for assessing fatty acid status but it is labour intensive and time consuming. Aims of the study [i] To describe and validate a rapid method, suitable for large scale population studies, for total blood fatty acid assay; [ii] to verify a possible correlation between total n-6:n-3 ratio and AA:EPA ratios in RBC phospholipids and in whole-blood total lipids, [iii] to assess usefulness of these ratio as biomarkers of LCPUFA status. Methods 1 Healthy volunteers and patients with various pathologies were recruited. 2 Fatty acid analyses by GC of methyl esters from directly derivatized whole blood total lipids and from RBC phospholipids were performed on fasting blood samples from 1432 subjects categorised according to their age, sex and any existing pathologies. AA:EPA ratio and the total n-6:n-3 ratio were determined. Results AA:EPA ratio is a more sensitive and reliable index for determining changes in total blood fatty acid and it is correlated with the ratio derived from extracted RBC phospholipids. Conclusions The described AA:EPA ratio is a simple, rapid and reliable method for determining n-3 fatty acid status.

  9. Ultrastructural immunocytochemical localization of chondroitin sulfate proteoglycan in Bruch's membrane of the rat

    DEFF Research Database (Denmark)

    Lin, W L; Essner, E; McCarthy, K J


    Two monoclonal antibodies (Mab 4D5 and 2D6) raised against the core protein of a basement membrane chondroitin sulfate proteoglycan from Reichert's membrane of the rat, were used for ultrastructural immunoperoxidase localization of this protein in Bruch's membrane of the rat. Immunoreactivity for...... for both antibodies was found in the basal lamina (basement membrane) of the choriocapillary endothelium and retinal pigment epithelium, in collagen fibers in the collagenous zones, and surrounding the elastic layer....

  10. Deforming Etna's Basement: Implications for Edifice stability. (United States)

    Bakker, Richard; Benson, Philip; Vinciguerra, Sergio


    At over 3 kilometers in height, Mt. Etna (Italy) is the largest volcano of continental Europe. The volcano formed on top of the alpine fold and thrust belt, with basaltic outflows lying unconformably on top of an alternation between sandstones, limestones and clays. Presently Etna's eastern flank is moving with speeds up to 2cm/yr to the east [Tibaldi and Groppelli, 2002]. It is the sequence of layers below the volcano that is thought to provide a complex, structurally controlled, mechanism to the volcano deformation as a whole. This is due to the interplay of gravitational forces, volcanic pressurization, and regional tectonics, which combine to play a complex role that remains poorly understood, especially when the physical and mechanical properties of the rocks are considered. In this study, we concentrate on the rock mechanical component, and in particular the formation known as Comiso Limestone. This limestone forms of one of the key lithologies of Etna's basement. The formation has been suggested to be affected by thermal weakening [Heap et al., 2013]. Previous work on Comiso Limestone suggests brittle behavior for the range of temperatures (up to 760 ˚C) and a significant reduction in strength with higher temperatures. [Mollo et al., 2011]. Chiodini et al [2011], speculate carbonate assimilation. This implies that the Carbondioxide created by decarbonatization, is able to escape. Using an internally heated "Paterson" type pressure vessel, we recreated conditions at 2-4 km depth (50-100 MPa) and using an anomalously high geotherm, as expected in volcanic settings (ranging from room to 600 ˚C). With the addition of confining pressure, we show a brittle to ductile transition occurs at a relatively low temperature of 300 ˚C. A significant decrease in strength occurs when the rock is exposed to temperatures exceeding 400 ˚C. In addition, we observe a significant difference in mechanical behavior between vented and unvented situations when decarbonatization is

  11. Building America Top Innovations 2012: Basement Insulation Systems

    Energy Technology Data Exchange (ETDEWEB)



    This Building America Top Innovations profile describes research on basement insulation, which identifies the wall installation methods and materials that perform best in terms of insulation and water resistance.

  12. Basement configuration of KG offshore basin from magnetic anomalies (United States)

    Subrahmanyam, V.; Swamy, K. V.; Raj, Neetha


    Marine magnetic anomalies along three representative profiles falling between shelf break and continent-ocean boundary in the offshore Krishna-Godavari basin were quantitatively interpreted for understanding the nature and structure of the magnetic basement using inversion technique. The interpretation of the anomalies shows that the magnetic basement lies deeper than the base of the sediments, i.e., acoustic basement identified by the seismic studies. This interpretation also shows that the magnetic basement is faulted along the NW-SE direction with the upthrown side lying to the north of the anomaly trend of this region. The coincidence of magnetizations observed through the present interpretation with that of charnockites of neighbouring EGMB and onshore K-G basin areas indicates that EGMB geology (charnockites, granitic gneiss, etc.) extends up to COB in the offshore K-G basin.

  13. Reviewing the pathogenesis of antibody-mediated rejection and renal graft pathology after kidney transplantation. (United States)

    Morozumi, Kunio; Takeda, Asami; Otsuka, Yasuhiro; Horike, Keiji; Gotoh, Norihiko; Narumi, Shunji; Watarai, Yoshihiko; Kobayashi, Takaaki


    The clinicopathological context of rejection after kidney transplantation was well recognized. Banff conferences greatly contributed to elucidate the pathogenesis and to establish the pathologic criteria of rejection after kidney transplantation. The most important current problem of renal transplantation is de novo donor-specific antibody (DSA) production leading chronic rejection and graft loss. Microvascular inflammation is considered as a reliable pathological marker for antibody-mediated rejection (AMR) in the presence of DSA. Electron microscopic study allowed us to evaluate early changes in peritubular capillaries in T-lymphocyte mediated rejection and transition to antibody-mediated rejection. Severe endothelial injuries with edema and activated lymphocyte invaded into subendothelial space with early multi-layering of peritubular capillary basement membrane suggest T-lymphocyte mediated rejection induce an unbounded chain of antibody-mediated rejection. The risk factors of AMR after ABO-incompatible kidney transplantation are important issues. Anti-ABO blood type antibody titre of IgG excess 32-fold before transplant operation is the only predictable factor for acute AMR. Characteristics of chronic active antibody-mediated rejection (CAAMR) are one of the most important problems. Light microscopic findings and C4d stain of peritubular capillary and glomerular capillary are useful diagnostic criteria of CAAMR. Microvascular inflammation, double contour of glomerular capillary and thickening of peritubular capillary basement are good predictive factors of the presence of de novo DSA. C4d stain of linear glomerular capillary is a more sensitive marker for CAAMR than positive C4d of peritubular capillary. Early and sensitive diagnostic attempts of diagnosing CAAMR are pivotal to prevent chronic graft failure.

  14. Basement domain map of the conterminous United States and Alaska (United States)

    Lund, Karen; Box, Stephen E.; Holm-Denoma, Christopher S.; San Juan, Carma A.; Blakely, Richard J.; Saltus, Richard W.; Anderson, Eric D.; DeWitt, Ed


    The basement-domain map is a compilation of basement domains in the conterminous United States and Alaska designed to be used at 1:5,000,000-scale, particularly as a base layer for national-scale mineral resource assessments. Seventy-seven basement domains are represented as eighty-three polygons on the map. The domains are based on interpretations of basement composition, origin, and architecture and developed from a variety of sources. Analysis of previously published basement, lithotectonic, and terrane maps as well as models of planetary development were used to formulate the concept of basement and the methodology of defining domains that spanned the ages of Archean to present but formed through different processes. The preliminary compilations for the study areas utilized these maps, national-scale gravity and aeromagnetic data, published and limited new age and isotopic data, limited new field investigations, and conventional geologic maps. Citation of the relevant source data for compilations and the source and types of original interpretation, as derived from different types of data, are provided in supporting descriptive text and tables.

  15. Magnetic resonance imaging assessment of labyrinthine pathology

    Energy Technology Data Exchange (ETDEWEB)

    Marsot-Dupuch, K. [Hopital Saint-Antoine, Service de Radiologie, 75 - Paris (France); Vignaud, J. [Val de Grace, Hopital d`Instruction du Service de Sante des Armees, 75 - Paris (France); Mehdi, M. [Hopital Saint-Antoine, Service de Radiologie, 75 - Paris (France); Pharaboz, C. [Hopital Begin, Hopital d`Instruction des Armees, 94 - Saint-Mande (France); Meyer, B. [Hopital Saint-Antoine, Service d`ORL, 75 - Paris (France)


    Membranous labyrinth pathologies are quite rare. They were until recently difficult to demonstrate by imaging technics, CT being the modality of choice. Our purpose was to stress the interest of MR examination for investigating patients complaining of vertigo, tinnitus, and profound sensorineural hearing loss. Normal anatomy as well as the main pathologically encountered changes are illustrated. (orig.)

  16. 新生儿肺透明膜病12例尸检病理分析%Pathological analysis of 12 cases of neonatal pulmonary transparent membrane disease

    Institute of Scientific and Technical Information of China (English)

    杨晓荣; 郑洪; 谭娜


    目的:探讨新生儿肺透明膜病(neonatal hyaline membrane disease,NHMD)的发生机制、临床病理特点及提高对NHMD的认识,以保证正常医疗次序的进行。方法:回顾性分析遵义医学院附属医院病理科2009年1月至2015年12月12例NHMD的临床及尸检病理资料。结果:12例NHMD中女婴3例、男婴9例;生存期8 h~3 d,其中早产儿9例、剖宫产儿3例;12例NHMD出生时一般情况尚好,均于出生后6 h内出现进行性呼吸困难、青紫、呼气性呻吟、吸气性三凹征,并呼吸衰竭死亡。病理改变均出现肺泡管壁、终末毛细支气管壁上有一层透明的均匀无结构或颗粒状嗜伊红膜样物附着。结论:NHMD多发生于早产儿,发病机制除了肺泡表面活性物质的不足以外,还认为是自由基的产生和氧化应激的炎症过程,同时加强孕产保健及提高对该病的认识极为重要,以减少新生儿病死率及医疗纠纷。%Objective: To explore the pathogenesis, clinicopathological characteristics neonatal hyaline membrane disease (NHMD), improves the cognition of NHMD, and increase diagnosis level.Methods: Retrospective analysis underwent in 12 NHMD cases of clinical and pathological data in the Pathology Department of Affliated Hospital of Zunyi Medical College from January 2009 to December 2015.Results: hTere were 3 cases of female and 9 cases of male in 12 cases NHMD; survival period was ranging from 8 hours to 3 days; the 12 cases including 9 cases of premature infants, 3 cases of cesarean section. All 12 cases were in good condition when they were born. In 6 hours after birth, they presented with progressive dyspnea, cyanosis, breath groan, and eventually died of respiratory failure. hTe pathological changes indicated a alveolar, end bronchial capillary wall with a layer of transparent uniform structure or granular eosinophilic membrane attachment.Conclusion: NHMD was usually occured in premature infant

  17. Examination of the Basement of Historic Buildings in Investment Activity

    Directory of Open Access Journals (Sweden)

    Ulybin Aleksey


    Full Text Available The process and methodology of the survey of basements rarely mentioned in the various construction rules and regulations. Basically describes the procedure of conducting a detailed survey of some of the individual elements. These surveys are fundamental in nature, include a large number of estimates and require significant financial and time costs. Usually the purpose of these surveys is to check the state of the building as a whole, it’s safe operation or before starting of reconstruction. In the process of selecting areas of investment activity such large-scale survey is not possible. Needed a quick and inexpensive method intended for decision about investment in a particular object. At the same time, the survey should cover all the elements of the basement significantly affect the cost of reconstruction of the basement associated with his penetration. The article presents the general conception of conducting a rapid survey. The described methods and technologies applicable to the examination for the purpose of making decisions about investments in reconstruction of a basement level rooms. The composition of the works and their sequence. A comparison of the advantages and disadvantages of different methods. The practical examples. Scheme of conducting a rapid survey of the basement. The article analyzes the materials used in the construction of historic buildings in St. Petersburg.

  18. Basement structure of the Granada basin, Betic Cordilleras, southern Spain (United States)

    Morales, J.; Vidal, F.; De Miguel, F.; Alguacil, G.; Posadas, A. M.; Ibañez, J. M.; Guzmán, A.; Guirao, J. M.


    The analysis and interpretation of geophysical data (gravity and seismic reflection) has facilitated the definition of the Granada basin structure. The reflector showing the contact between the Betic-Subbetic basement and the Neogene-Quaternary sedimentary filling has been identified. Mapping of the basement in two and three dimensions is presented. The presence of four important depocenters (Genil, Chimeneas, Cubillas and Granada) has been determined. These troughs are limited by ridge areas through important sets of fractures. In some cases the accumulation of Neogene-Quaternary sediments reaches a thickness exceeding 3 km as in the Genii and Cubillas depocenters. The mapping of the most important fractures affecting the basement has been achieved, defining four systems that have influenced and conditioned the genesis and late evolution of the Granada basin. The directions of the most important groups of fractures are: NE-SW, N70W to E-W, N45W and N10-30E.

  19. Canine and feline oral pathology


    Costa, S.; Pais, B.; Almeida, D.; Simões, J.; Mega, A. C.; Vala, Helena


    The aim of this work was to present a brief review of the main conditions affecting the oral cavity of dogs and cats. In recent years there has been increased attention with regard to veterinary dentistry, being several and frequent the pathologies located in the oral cavity of our pets. These diseases mainly affect the teeth and the mucous membranes of the oral cavity, and may, in chronic cases, also affect vital organs. This condition could have different causes, including hereditary, conge...

  20. Review paper: a review of the pathology of abnormal placentae of somatic cell nuclear transfer clone pregnancies in cattle, sheep, and mice. (United States)

    Palmieri, C; Loi, P; Ptak, G; Della Salda, L


    Cloning of cattle, sheep, and mice by somatic cell nuclear transfer (SCNT) can result in apparently healthy offspring, but the probability of a successful and complete pregnancy is less than 5%. Failures of SCNT pregnancy are associated with placental abnormalities, such as placentomegaly, reduced vascularisation, hypoplasia of trophoblastic epithelium, and altered basement membrane. The pathogenesis of these changes is poorly understood, but current evidence implicates aberrant reprogramming of donor nuclei by the recipient oocyte cytoplast, resulting in epigenetic modifications of key regulatory genes essential for normal placental development. The purpose of this review is to provide an overview of the anatomic pathology of abnormal placentae of SCNT clones and to summarize current knowledge concerning underlying pathogenetic mechanisms.

  1. [Pathology of the vitreomacular interface]. (United States)

    Pop, Monica; Gheorghe, Alina


    Vitreous role in the pathophysiology of retinal diseases has increased importantly over the recent years. This was possible using Optical Coherence Tomography which reviewed the way the vitreoretinal interface should be looked at and defined and classified new pathologies such as Vitreoretinal Traction Syndrome. Vitreous is not an empty space but an important anatomical structure with role in ocular physiology. With age biochemical changes occur so that vitreous starts to liquefy. Once the vitreous is liquefied (sinchisis) it collapses and passes in the retrohialoid space (sineresis). In complete PVD besides sinchisis there is a weakness of the adherence between the posterior cortex and ILM with total detachment of posterior cortex. Abnormal adhesions are associated with incomplete PVD. The definition and understanting of vitreoretinal pathology is an active and continuous process, PVD being the trigger of a lot of retinal pathologies: epiretinal membrane, macular hole, tractional macular oedema, VMTS, myopic traction maculopathy, exacerbations of exudative ARMD.

  2. Magnetic basement in the central Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Sarma, K.V.L.N; Ramana, M.V.; Ramprasad, T.; Desa, M.; Subrahmanyam, V.; Krishna, K.S.; Rao, M.M.M.

    . The N10-12 degrees W trending subsurface 85 degrees E Ridge buried under 2 to 3 km thick sediments is a prominent tectonic feature. Offshore basins characterised by deeper magnetic basement (approx. 9 km) and 100-200 km wide are present on either sides...

  3. Curriculum Guidelines for Pathology and Oral Pathology. (United States)

    Journal of Dental Education, 1985


    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  4. Pathological patterns of mesangioproliferative glomerulonephritis seen at a tertiary care center

    Directory of Open Access Journals (Sweden)

    Mokhtar Ghadeer A.


    Full Text Available Background: Mesangioproliferative glomerulonephritis (MesPGN is a common morphological pattern that encompasses several groups of renal diseases including IgA nephropathy (IgAN, IgM nephropathy (IgMN, lupus nephritis (LN, C1q nephropathy (C1qN and other entities. Objectives: The aim of this study was to analyze the pathological findings and the clinical features of cases of MesPGN seen at the king Abdulaziz University, in Saudi Arabia. Patients and Methods: A total of 750 percutaneous native renal biopsies were seen at our institution from January 2000 to December 2011. All the cases diagnosed as MesPGN on light microscopy (LM were retrieved from the archives of pathology. The pathological features and the clinical data of these cases were reviewed. The clinical data was available for 80 cases only. Results: A total of 103 cases (14% met the inclusion criteria for the diagnosis of MesPGN. The most common diagnostic entity was IgMN (46.6% followed by IgAN (30% along with few cases of class II LN, C1qN, minimal change disease (MCD, Alport’s syndrome, focal segmental glomerulosclerosis (FSGS, thin basement membrane disease (TBMD, and fibrillary glomerulonephritis. The most common clinical presentation was nephrotic syndrome seen in 71% of 80 cases, followed by hematuria (14%. Histologically, focal mesangial proliferation was seen in 62% while diffuse proliferation was seen in 38% of the cases. Conclusion: Mesangioproliferative glomerulonephritis is an important cause of nephrotic syndrome in young adults in the western region of Saudi Arabia. Future studies from the region are needed to elucidate the clinical relevance of mesangial cell proliferation to the end stage kidney diseases.

  5. Basement configuration of KG offshore basin from magnetic anomalies

    Indian Academy of Sciences (India)

    V Subrahmanyam; K V Swamy; Neetha Raj


    Marine magnetic anomalies along three representative profiles falling between shelf break and continent–ocean boundary in the offshore Krishna–Godavari basin were quantitatively interpreted for understandingthe nature and structure of the magnetic basement using inversion technique. The interpretation of theanomalies shows that the magnetic basement lies deeper than the base of the sediments, i.e., acousticbasement identified by the seismic studies. This interpretation also shows that the magnetic basementis faulted along the NW–SE direction with the upthrown side lying to the north of the anomaly trendof this region. The coincidence of magnetizations observed through the present interpretation with thatof charnockites of neighbouring EGMB and onshore K–G basin areas indicates that EGMB geology(charnockites, granitic gneiss, etc.) extends up to COB in the offshore K–G basin.

  6. The Grenville-age basement of the Andes (United States)

    Ramos, Victor A.


    The analysis of the basement of the Andes shows the strong Grenville affinities of most of the inliers exposed in the different terranes from Colombia to Patagonia. The terranes have different histories, but most of them participated in the Rodinia supercontinent amalgamation during the Mesoproterozoic between 1200 and 1000 Ma. After Rodinia break-up some terranes were left in the Laurentian side such as Cuyania and Chilenia, while others stayed in the Gondwanan side. Some of the terranes once collided with the Amazon craton remained attached, experiencing diverse rifting episodes all along the Phanerozoic, as the Arequipa and Pampia terranes. Some other basement inliers were detached in the Neoproterozoic and amalgamated again to Gondwana in the Early Cambrian, Middle Ordovician or Permian times. A few basement inliers with Permian metamorphic ages were transferred to Gondwana after Pangea break-up from the Laurentian side. Some of them were part of the present Middle America terrane. An exceptional case is the Oaxaquia terrane that was detached from the Gondwana margin after the Early Ordovician and is now one of the main Mexican terranes that collided with Laurentia. These displacements, detachments, and amalgamations indicate a complex terrane transfer between Laurentia and Gondwana during Paleozoic times, following plate reorganizations and changes in the absolute motion of Gondwana.

  7. The Danish Pathology Register

    DEFF Research Database (Denmark)

    Bjerregaard, Beth; Larsen, Ole B


    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  8. Retinal Damage Induced by Internal Limiting Membrane Removal

    Directory of Open Access Journals (Sweden)

    Rachel Gelman


    Full Text Available The internal limiting membrane (ILM, the basement membrane of the Müller cells, serves as the interface between the vitreous body and the retinal nerve fiber layer. It has a fundamental role in the development, structure, and function of the retina, although it also is a pathologic component in the various vitreoretinal disorders, most notably in macular holes. It was not until understanding of the evolution of idiopathic macular holes and the advent of idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the treatment of tractional maculopathies was explored. Today intentional ILM peeling is a commonly applied surgical technique among vitreoretinal surgeons as it has been found to increase the rate of successful macular hole closure and improve surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined surgery for tractional maculopathies, like all surgical procedures it is not immune to perioperative risk. The essential role of the ILM to the integrity of the retina and risk of trauma to retinal tissue spurs suspicion with regard to its routine removal. Several authors have investigated the retinal damage induced by ILM peeling and these complications have been manifested across many different diagnostic studies.

  9. Human Amnion Membrane Serves as a Substratum for Growing Axons in vitro and in vivo (United States)

    Davis, George E.; Blaker, Scott N.; Engvall, Eva; Varon, Silvio; Manthorpe, Marston; Gage, Fred H.


    The epithelial cell layer of human amnion membrane can be removed while the basement membrane and stromal surfaces remain morphologically intact. Such a preparation has been used as a substratum for the in vitro culture of dissociated neurons. Embryonic motor neurons from chick ciliary ganglion attached to both surfaces but grew extensive neurites only on the basement membrane. On cross sections of rolled amnion membranes, regenerating axons of cultured neurons were guided along pathways of basement membrane that were immunoreactive with an antibody to laminin. In addition, when rolled amnion membranes were implanted into a lesion cavity between the rat septum and hippocampus, cholinergic neurons extended axons through the longitudinally oriented implant into the hippocampus. Thus, this amnion preparation can serve as a bridge to promote axonal regeneration in vivo in damaged adult brain.

  10. Immunohistochemical study of pathological alterations of peritoneum in patients with terminal renal insufficiency and on peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Trbojević-Stanković Jasna


    Full Text Available Background/Aim. During peritoneal dialysis (PD an exchange of substances between blood and dialysate takes place through specific histological structures of peritoneum. Peritoneal double-layered serous membrane has, so far, mostly been studied with electron microscopy on experimental animals. The aim of this study was to assess integrity of peritoneal tissue in end-stage renal disease (ESRD and PD patients using standard light microscopy and immunohistochemical methods. Methods. Peritoneal tissue biopsies were performed on 25 persons: 8 healthy donors during nephrectomy, 9 ESRD patients upon insertion of PD catheter, and 8 PD patients upon removal of the catheter for medical indications. The samples were fixed and prepared routinely for immunocytochemical staining by standardized streptavidin biotin AEC method using a LSAB2® HRP kit (Dako®, Denmark for collagen IV and analyzed by light microscopy. Results. We observed mesothelial detachment from lamina propria, duplicated basement membrane and much thicker blood vessel walls in ESRD and PD patients, compared to healthy subjects. Differences in histological structure, emphasized with immunostaining, indicated pathological alterations of peritoneal tissue in the renal patients. Conclusions. Imunohistochemistry can be used in studying histological alterations of peritoneal tissue in ESRD and PD patients. This method may indicate possible problems in filtration and secretion processes in this tissue.

  11. Morphological features of pathological membrane of inferior vena cava associated with Budd-Chiari syndrome%布-加综合征下腔静脉病变隔膜形态学特征研究

    Institute of Scientific and Technical Information of China (English)

    乔师师; 党晓卫; 徐大千; 吴阳; 李捷; 张红新; 陈奎生; 许培钦; 张水军


    microscopy.Results The diseased diaphragms were located within 2.0 cm from the junction of the IVC and the right atrium.The diaphragms had thick edges and relatively thin centers; their surface connected with the inner membrane of the IVC.A mural thrombus was observed in the IVC below the diaphragm in nine patients,with partial calcification of the diaphragm in five patients.Light microscopy revealed that the diaphragm was composed of massive homogencous collagen fibers and fibroblasts.The collagen was highly disorganized and some collagen fibers showed hyaline degeneration.The edges of the diaphragms showed proliferation of fibrous connective tissue,together with some pathological changes,including the presence of some granulation tissue and neovessels.The structures of the normal inner,middle and outer membranes of the IVC remained intact.Electron microscopy revealed the diaphragms contained a relatively high number of fibroeytes,and a small number of endotheliocytes on their surface.Most of the cristae inside the endotheliocytes were disconnected from the inner membranes and fused,and were therefore blurred or missing,The rough endoplasmic reticulum was also slightly dilated.Apoptotic cells were infrequent,and were generally smaller than expected.The endotheliocytes on the normal IVC walls were well organized,showing a striped distribution.Mitochondria,rough endoplasmic reticolum and pinocytotic vesicles were found inside the endotheliocytes.Collageo fibers and elastic fibers below the endotheliocytes were sparse.Conclusion The diseased IVC diaphragm associated with Budd Chiari syndrome mainly develops as a result of fibrocyte proliferation,although IVC injury and inflammatory reactions may also be involved.

  12. 老年人原发性膜性肾病肾小动脉病变的特点%The pathological changes of renal arterioles in the elderly with idiopathic membranous nephropathy

    Institute of Scientific and Technical Information of China (English)

    王艺萍; 王梅; 王素霞; 鄂洁; 郑欣


    目的 观察老年原发性膜性肾病患者肾小动脉病变的发生情况及其特点.方法 选取2000年1月至2005年12月在我院住院并经肾穿刺活检确诊的原发性膜性肾病患者168例,分为老年组(≥60岁)和非老年组(<60岁),分析两组患者肾小动脉病变的发生情况及其影响因素.结果 老年组收缩压、舒张压、血肌酐水平、血尿发生率显著高于非老年组,而eGFR则显著低于非老年组.肾小球球性或节段硬化的比例以及肾小管萎缩和肾间质纤维化程度老年组重于非老年组.肾脏小动脉病变的发生率以及严重程度均明显重于非老年组.多因素分析显示,高血压、年龄、肾小管间质慢性损伤是肾脏小动脉病变发生的独立影响因素.进一步将血压正常且小管间质病变匹配的老年与非老年组患者比较,老年患者.肾小动脉病变的发生率以及严重程度仍重于非老年患者(P<0.05),肾小动脉病变表现为肌层增厚,合并玻璃样变的比例高.结论 老年原发性膜性肾病患者肾小动脉病变的发生率以及严重程度均明显高于非老年患者,合并玻璃样变的比率高,其可能是影响老年原发性肾脏病患者预后不良的重要因素.%Objective To observe the pathological changes of renal arterioles in the elderly with idiopathic membranous nephropathy. Methods One hundred and sixty-eight patients with clinical and biopsy-proven idiopathic membranous nephropathy from Jan 2000 to Dec 2005 were enrolled.The characteristics and influence factors of the renal arterioles lesions in the elderly group(44 cases)and non-elderly group(124 cases)were analyzed. Results The systolic blood pressure.diastolic blood pressure.the level of serum creatinine and the incidenee of hematuria were higher in the elderly group,but the eGFR was lower.The ratios of global and segmental glomerulosclerosis and degrees of tubular interstitial damage and fibrosis were more severe in the

  13. Basement faults and volcanic rock distributions in the Ordos Basin

    Institute of Scientific and Technical Information of China (English)


    Volcanic rocks in the Ordos Basin are of mainly two types: one in the basin and the other along the margin of the basin. Besides those along the margin, the marginal volcanic rocks also include the volcanic rocks in the Yinshanian orogenic belt north of the basin. Based on the latest collection of gravitational and aeromagnetic data, here we interpret basement faults in the Ordos Basin and its peripheral region, compare the faults derived from aeromagnetic data with those from seismic data, and identify the geological ages of the fault development. Two aeromagnetic anomaly zones exist in the NE-trending faults of the southern basin, and they are in the volcanic basement formed in pre-Paleozoic. These NE-trending faults are the channel of volcanic material upwelling in the early age (Archean-Neoproterozoic), where igneous rocks and sedimentary rocks stack successively on both sides of the continental nucleus. In the Cambrian, the basin interior is relatively stable, but in the Late Paleozoic and Mesozoic, the basin margin underwent a number of volcanic activities, accompanied by the formation of nearly north-south and east-west basement faults in the basin periphery and resulting in accumulation of great amount of volcanic materials. Volcanic tuff from the basin periphery is discovered in the central basin and volcanic materials are exposed in the margins of the basin. According to the source-reservoir-cap rock configuration, the basin peripheral igneous traps formed in the Indosinian-Early Yanshanian and Late Hercynian are favorable exploration objectives, and the volcanic rocks in the central basin are the future target of exploration.

  14. Formation and Evolution of the Junggar basin basement (United States)

    He, D.


    Junggar Basin is located in the central part of the Central Asian Orogenic Belt (CAOB). Its basement nature is a highly controversial scientific topic, involving the basic style and processes of crustal growth.Based on the borehole data from over 300 wells drilled into the Carboniferous System, together with the high-resolution gravity and magnetic data (in a 1:50,000 scale), we made a detailed analysis of the basement structure, formation timing and process and later evolution on basis of core geochemical and isotopic analysis. Firstly, we defined the Mahu Precambrian micro-continental block in the juvenile crust of Junggar Basin according to the Hf isotopic analysis of the Carboniferous volcanic rocks. Secondly, the results of the tectonic setting and basin analysis suggest that the Junggar area incorporates three approximately E-W trending island arc belts (from north to south: Yemaquan-Wulungu-Chingiz, Jiangjunmiao-Luliang-Darbut and Zhongguai-Mosuowan-Baijiahai-Qitai respectively) and intervened three approximately E-W trending retro-arc or inter-arc basin belts from north to south, such as Santanghu-Suosuoquan-Emin, Wucaiwan-Dongdaohaizi-Mahu (Mahu block sunk as a bathyal basin during this phase) and Fukang-western well Pen1 accordingly. Thirdly, the closure of these retro-arc or inter-arc basins gradually toward the south led to the occurrence of collision and amalgamation of the above-mentioned island arcs during the Carboniferous, constituting the basic framework of the Junggar "block". Fourthly, the emplacement of large-scale mantle-derived magmas occurred in the latest Carboniferous or Early Permian. For instance, the well Mahu 5 penetrate the latest Carboniferous basalts with a thickness of over 20m, and these mantle-derived magmas concreted the above-mentioned island arc-collaged body. Therefore, the Junggar basin basement mainly comprises pre-Carboniferous collaged basement, and its formation is characterized by two-stage growth model, involving the

  15. Ordovician Basement Hydrocarbon Reservoirs in the Tarim Basin, China

    Institute of Scientific and Technical Information of China (English)

    YAN Xiangbin; LI Tiejun; ZHANG Tao


    Ordovician marine carbonate basement traps are widely developed in the paleo-highs and paleo-slopes in the Tarim Basin. Reservoirs are mainly altered pore-cavity-fissure reservoirs. Oil sources are marine carbonate rocks of the Lower Paleozoic. Thus, the paleo-highs and paleo-slopes have good reservoiring conditions and they are the main areas to explore giant and large-scale oil reservoirs. The main factors for their reservoiring are: (1) Effective combination of fenestral pore-cavity-fracture reservoirs, resulting from multi-stage, multi-cyclic karstification (paleo-hypergene and deep buried) and fracturing, with effective overlying seals, especially mudstone and gypsum mudstone in the Carboniferous Bachu Formation, is essential to hydrocarbon reservoiring and high and stable production; (2) Long-term inherited large rises and multi-stage fracture systems confine the development range of karst reservoirs and control hydrocarbon migration, accumulation and reservoiring; (3) Long-term multi-source hydrocarbon supply, early reservoiring alteration and late charging adjustment are important reservoiring mechanisms and determine the resource structure and oil and gas properties. Favorable areas for exploration of Ordovician carbonate basement hydrocarbon reservoirs in the Tarim Basin are the Akekule rise, Katahe uplift, Hetianhe paleo-high and Yakela faulted rise.

  16. Provenance of Neoproterozoic sedimentary basement of northern Iran, Kahar Formation (United States)

    Etemad-Saeed, Najmeh; Hosseini-Barzi, Mahboubeh; Adabi, Mohammad Hossein; Sadeghi, Abbas; Houshmandzadeh, Abdolrahim


    This article presents new data to understand the nature of the hidden crystalline basement of northern Iran and the tectonic setting of Iran during late Neoproterozoic time. The siliciclastic-dominated Kahar Formation represents the oldest known exposures of northern Iran and comprises late Ediacaran (ca. 560-550 Ma) compositionally immature sediments including mudrocks, sandstones, and conglomerates. This work focuses on provenance of three well preserved outcrops of this formation in Alborz Mountains: Kahar Mountain, Sarbandan, and Chalus Road, through petrographic and geochemical methods. Mineralogical Index of Alteration (MIA) and Chemical Index of Alteration (CIA-after correction for K-metasomatism) values combined with A-CN-K relations suggest moderate weathering in the source areas. The polymictic nature of Kahar conglomerates indicates a mixed provenance for them. However, modal analysis of Kahar sandstones (volcanic to plagioclase-rich lithic arkose) and whole rock geochemistry of mudrocks suggest that they are largely first-cycle sediments and that their sources were remarkably late Ediacaran, intermediate-felsic igneous rocks from proximal arc settings. Tectonic setting discrimination diagrams also indicate a convergent plate margin and continental arc related basin for Kahar sediments. This interpretation is supported by the phyllo-tectic to tectic composition and geochemistry of mudrocks. These results reveal the presence of a felsic/intermediate subduction-related basement (∼600-550 Ma) in this region, which provides new constraints on subduction scenario during this time interval in Iran, as a part of the Peri-Gondwanan terranes.

  17. Podocyte Pathology and Nephropathy

    Directory of Open Access Journals (Sweden)

    Sandra eMerscher


    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  18. Structural analysis of a fractured basement reservoir, central Yemen (United States)

    Veeningen, Resi; Rice, Hugh; Schneider, Dave; Grasemann, Bernhard; Decker, Kurt


    The Pan-African Arabian-Nubian Shield (ANS), within which Yemen lies, formed as a result of Neoproterozoic collisional events between c. 870-550 Ma. Several subsequent phases of extension occurred, from the Mesozoic (due to the breakup of Gondwana) to the Recent (forming the Gulf of Aden and the Red Sea). These resulted in the formation of numerous horst- and-graben structures and the development of fractured basement reservoirs in the southeast part of the ANS. Two drill cores from the Mesozoic Marib-Shabwa Basin, central Yemen, penetrated the upper part of the Pan-African basement. The cores show both a lithological and structural inhomogeneity, with variations in extension-related deformation structures such as dilatational breccias, open fractures and closed veins. At least three deformation events have been recognized: D1) Ductile to brittle NW-SE directed faulting during cooling of a granitic pluton. U-Pb zircon ages revealed an upper age limit for granite emplacement at 627±3.5 Ma. As these structures show evidence for ductile deformation, this event must have occurred during the Ediacaran, shortly after intrusion, since Rb/Sr and (U-Th)/He analyses show that subsequent re-heating of the basement did not take place. D2) The development of shallow dipping, NNE-SSW striking extensional faults that formed during the Upper Jurassic, simultaneously with the formation of the Marib-Shabwa Basin. These fractures are regularly cross-cut by D3. D3) Steeply dipping NNE-SSW to ENE-WSW veins that are consistent with the orientation of the opening of the Gulf of Aden. These faults are the youngest structures recognized. The formation of ductile to brittle faults in the granite (D1) resulted in a hydrothermally altered zone ca. 30 cm wide replacing (mainly) plagioclase with predominantly chlorite, as well as kaolinite and heavy element minerals such as pyrite. The alteration- induced porosity has an average value of 20%, indicating that the altered zone is potentially a

  19. Application of Molecular Pathology in Endocrine Pathology. (United States)

    Linke, Ebru Serinsoz; Tezel, Gaye Güler


    Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.


    Directory of Open Access Journals (Sweden)

    E.N. Sidorova


    Full Text Available Article contains description of structure of regional finance resources, discloses the sources of financing, describes the role of budgeting. Problems and possible ways of solution of inter-budget relationships optimisation are described with the purpose of increasing of financial prosperity of territories. Overall role of optimisation as one of the most important factors of strengthening of financial basement of territories is described along with the necessity of considering the budget process as stimulated factor for regional economic systems development. Suggestions on substitution of cost method of budget resources management by the model of outcomes management and further development of mechanisms of territorial bodies interaction with economic entities on the base of state-private partnership were proposed.

  1. Basement structures over Rio Grande Rise from gravity inversion (United States)

    Constantino, Renata Regina; Hackspacher, Peter Christian; de Souza, Iata Anderson; Lima Costa, Iago Sousa


    The basement depth in the Rio Grande Rise (RGR), South Atlantic, is estimated from combining gravity data obtained from satellite altimetry, marine surveys, bathymetry, sediment thickness and crustal thickness information. We formulate a crustal model of the region by inverse gravity modeling. The effect of the sediment layer is evaluated using the global sediment thickness model of National Oceanic and Atmospheric Administration (NOAA) and fitting the sediment compaction model to observed density values from Deep Sea Drilling Project (DSDP) reports. The Global Relief Model ETOPO1 and constraining data from seismic interpretation on crustal thickness are integrated in the inversion process. The modeled Moho depth values vary between 6 and 27 km over the area, being thicker under the RGR and also in the direction of São Paulo Plateau. The inversion for the gravity-equivalent basement topography is applied to gravity residual data, which is free from the gravity effect of sediments and from the gravity effect of the estimated Moho interface. We find several short-wavelengths structures not present in the bathymetry data. Our model shows a rift crossing the entire Rio Grande Rise deeper than previously presented in literature, with depths up to 5 km in the East Rio Grande Rise (ERGR) and deeper in the West Rio Grande Rise (WRGR), reaching 6.4 km. An interesting NS structure that goes from 34°S and extends through de São Paulo Ridge may be related to the South Atlantic Opening and could reveal an extinct spreading center.

  2. Immunochemical and ultrastructural assessment of the nature of the pericellular basement membrane of human decidual cells

    DEFF Research Database (Denmark)

    Wewer, U M; Faber, M; Liotta, L A


    -linked immunosorbent assay. Biosynthesis of laminin was shown by [35S]methionine labeling of short term organ cultures of decidual tissue followed by immunoprecipation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography. The laminin chains migrated with the apparent molecular weights of 300...


    NARCIS (Netherlands)



    To identify in tissue sections the relative positions of antigen distributions close to the resolving power of the microscope, we have developed the fluorescence overlay antigen mapping (FOAM) procedure. As this technique makes high demands on the geometric fidelity of the overlay image, it is essen

  4. In vivo turnover of the basement membrane and other heparan sulfate proteoglycans of rat glomerulus

    DEFF Research Database (Denmark)

    Beavan, L A; Davies, M; Couchman, J R


    at defined times (0-163 h) the kidneys were perfused in situ with 0.01% cetylpyridinium chloride in phosphate-buffered saline to maximize the recovery of 35S-proteoglycans. Glomeruli were isolated from the renal cortex and analyzed for 35S-proteoglycans by autoradiographic, biochemical, and immunochemical...

  5. Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress

    Directory of Open Access Journals (Sweden)

    Wilhelm eKriz


    Full Text Available Podocytes are lost by detachment from the GBM as viable cells; details are largely unknown. We studied this process in the rat after growth stimulation with FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes underwent hypertrophy, but, in the long run, developed various changes that could either be interpreted showing progressing stages in detachment from the GBM or stages leading to a tighter attachment by foot process effacement (FPE. This occurred in microdomains within the same podocyte; thus features of detachment and of reinforced attachment may simultaneously be found in the same podocyte.(1 Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e. expansions of the subpodocyte space.(2 Podocytes entered the process of FPE starting with the retraction of foot processes and the replacement of the slit diaphragm by occluding junctions thereby sealing the filtration slits. Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3 Failure of sealing the slits led to gaps of varying width between retracting foot processes facilitating the outflow of the filtrate from the GBM.(4 Since those gaps are frequently overarched by broadened primary processes the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM.(5 The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space. Multiple flow resistances in series likely generated an expansile force on podocytes contributing to detachment.(6 Such a situation appears to proceed to complete disconnection generally of a group of podocytes owing to the junctional connections between them. (7 Since such groups of detaching podocytes generally make contact to parietal cells, they start the formation of tuft adhesions to Bowman's capsule.

  6. Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress. (United States)

    Kriz, Wilhelm; Hähnel, Brunhilde; Hosser, Hiltraud; Rösener, Sigrid; Waldherr, Rüdiger


    Podocytes are lost by detachment from the GBM as viable cells; details are largely unknown. We studied this process in the rat after growth stimulation with FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes underwent hypertrophy, but, in the long run, developed various changes that could either be interpreted showing progressing stages in detachment from the GBM or stages leading to a tighter attachment by foot process effacement (FPE). This occurred in microdomains within the same podocyte; thus, features of detachment and of reinforced attachment may simultaneously be found in the same podocyte. (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes entered the process of FPE starting with the retraction of foot processes (FPs) and the replacement of the slit diaphragm by occluding junctions, thereby sealing the filtration slits. Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits led to gaps of varying width between retracting FPs facilitating the outflow of the filtrate from the GBM. (4) Since those gaps are frequently overarched by broadened primary processes, the drainage of the filtrate into the Bowman's space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM. (5) The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman's space. Multiple flow resistances in series likely generated an expansile force on podocytes contributing to detachment. (6) Such a situation appears to proceed to complete disconnection generally of a group of podocytes owing to the junctional connections between them. (7) Since such groups of detaching podocytes generally make contact to parietal cells, they start the formation of tuft adhesions to Bowman's capsule.

  7. Immunological characterization of a basement membrane-specific chondroitin sulfate proteoglycan

    DEFF Research Database (Denmark)

    McCarthy, K J; Accavitti, M A; Couchman, J R


    -[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate buffer followed by cesium chloride density-gradient ultracentrifugation under dissociative conditions. The proteoglycans were subsequently purified from the two most dense fractions (greater than 1.3 g/ml) by ion-exchange chromatography. Mice were immunized...... with the proteoglycan preparation and four mAbs recognizing the core protein of a high-density, buoyant chondroitin sulfate proteoglycan were raised. Confirmation of antibody specificity was carried out by the preparation of affinity columns made from each of the mAbs. Chondroitin sulfate proteoglycans (CSPGs) were...... (Mr = 5-6 x 10(5)), with a core protein of Mr = approximately 1.5-1.6 x 10(5) and composed exclusively of chondroitin sulfate chains with an average Mr = 1.6-1.8 x 10(4). In addition, a CSPG was purified from adult rat kidney, whose core protein was also Mr = 1.6 x 10(5). The proteoglycan and its core...

  8. Rac1 is essential for basement membrane-dependent epiblast survival

    DEFF Research Database (Denmark)

    He, Xiaowen; Liu, Jie; Qi, Yanmei


    biological process are largely unknown. Here we demonstrate that Rac1 ablation in embryonic stem cell-derived embryoid bodies (EBs) leads to massive apoptosis of epiblast cells in contact with the BM. Expression of wild-type Rac1 in the mutant EBs rescues the BM-contacting epiblast, while expression...

  9. Basement membrane components secreted by mouse yolk sac carcinoma cell lines

    DEFF Research Database (Denmark)

    Damjanov, A; Wewer, U M; Tuma, B


    carcinoma respectively. Cell lines NE and ME were composed of a monomorphous cell population; however, the morphology of ME was growth-medium-dependent. LRD was composed of a heterogeneous cell population and formed embryoid bodies. NE secreted soluble laminin, osteonectin, entactin and fibronectin but did...

  10. Pathology in Greece. (United States)

    Sakellariou, S; Patsouris, E


    Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

  11. Basement domain map of the conterminous U.S.A. and Alaska (United States)

    U.S. Geological Survey, Department of the Interior — The basement-domain map is a compilation of basement domains in the conterminous United States and Alaska designed to be used at 1:5,000,000-scale, particularly as a...

  12. Basement domain map of the conterminous U.S.A. and Alaska (United States)

    U.S. Geological Survey, Department of the Interior — The basement-domain map is a compilation of basement domains in the conterminous United States and Alaska designed to be used at 1:5,000,000-scale, particularly as...

  13. Basement structure beneath the innershelf off Mahabalipuram to Palar River, east coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Murthy, K.S.R.; Venkateswarlu, K.; Rao, T.C.S.

    (30 m). The folded nature of the basement is still prevalent at greater depth (50-60 m) off Palar River whereas further north towards Mahabalipuram the basement appears to be smooth at greater depths. The results indicate that Palar River is associated...

  14. The spatial organization of Descemet's membrane-associated type IV collagen in the avian cornea



    The organization of type IV collagen in the unconventional basement membrane of the corneal endothelium (Descemet's membrane) was investigated in developing chicken embryos using anti-collagen mAbs. Both immunofluorescence histochemistry and immunoelectron microscopy were performed. In mature embryos (greater than 15 d of development), the type IV collagen of Descemet's membrane was present as an array of discrete aggregates of amorphous material at the interface between Descemet's membrane a...

  15. Hip joint pathology

    DEFF Research Database (Denmark)

    Tijssen, M; van Cingel, R E H; de Visser, E


    The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18-6...

  16. Membrane dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin


    Current topics include membrane-protein interactions with regard to membrane deformation or curvature sensing by BAR domains. Also, we study the dynamics of membrane tubes of both cells and simple model membrane tubes. Finally, we study membrane phase behavior which has important implications...... for the lateral organization of membranes as wells as for physical properties like bending, permeability and elasticity...

  17. The Role of Laminin α4 in Human Umbilical Vein Endothelial Cells and Pathological Mechanism of Preeclampsia. (United States)

    Shan, Nan; Zhang, Xuemei; Xiao, Xiaoqiu; Zhang, Hua; Chen, Ying; Luo, Xin; Liu, Xiru; Zhuang, Baimei; Peng, Wei; Qi, Hongbo


    Preeclampsia (PE) is associated with defective placental angiogenesis and poor placentation. Laminins are the main noncollagenous glycoproteins in basement membranes, and laminin α4 (LAMA4) promotes the migration, proliferation, and survival of various cells. The primary purpose of this study is to investigate the role of LAMA4 in human umbilical vein endothelial cells (HUVECs) function during the development of PE. We found expression levels of LAMA4 in human PE placentas were significantly lower compared to the control placentas. The LAMA4 small-interfering RNA transfection and hypoxia-reoxygenation (H/R) intervention reduced the migratory and tube formation abilities of HUVECs. The mitogen-activated protein kinase (MAPK) signaling pathways interacted with LAMA4 expression and H/Rexposure led to MAPK pathways activation in HUVECs. We demonstrated that LAMA4 is very crucial in promoting the functions of endothelial cells. Oxidative stress plays a vital role in controlling expression of LAMA4 through MAPK signaling pathways, which suggests a possible pathological mechanism of PE.

  18. [Pathology- a new revival]. (United States)

    Barshack, Iris


    The field of pathology has undergone considerable change in recent years. The editor and editorial board of this journal are to be commended for their decision to devote a special issue to the field of pathology. Pathology deals with the characterization, investigation, and diagnosis of disease and disease processes and as such, has Long been considered one of the foundations of medicine. It is a rich and multi-faceted field which has retained its breadth of scope in the face of ever-increasing specialization and sub-specialization in medicine. In addition to its classic roles in autopsy, case description, and the diagnosis of pathoLogic processes, new and innovative spheres of activity are becoming integral to the field, especially in the realm of molecular pathology. Pathology is a Leading player in the new age of "personalized cancer therapy", where pathologists are responsible not only for diagnosing disease in the tissue, but also for conducting additional tests which may predict its response to specific drug therapies. In this context, moLecular pathology has become essential to the field both in the provision of cLinical service and research. To fully implement this trend, we are witness to the rise of tissue collection and tissue banking initiatives for both diagnostic and research purposes. A national tissue banking project in Israel has recently received considerable attention.

  19. [Gunshot wounds: forensic pathology]. (United States)

    Lorin de la Grandmaison, Geoffroy


    Gunshot wounds are among the most complex traumatic lesions encountered in forensic pathology. At the time of autopsy, careful scrutiny of the wounds is essential for correct interpretation of the lesions. Complementary pathological analysis has many interests: differentiation between entrance and exit wounds, estimation of firing distance, differentiation between vital and post mortem wounds and wounds dating. In case of multiple headshots, neuropathological examination can provide arguments for or against suicide. Sampling of gunshot wounds at autopsy must be systematic. Pathological data should be confronted respectively to autopsy and death scene investigation data and also ballistic studies. Forensic pathologist must be aware of the limits of optic microscopy.

  20. Magnetically inferred basement structure in central Saudi Arabia (United States)

    Johnson, Peter R.; Stewart, Ian C. F.


    A compilation of magnetic data acquired during the past three decades for a region in central Saudi Arabia where Precambrian basement is partly exposed on the Arabian shield and partly concealed by overlying Phanerozoic strata, shows a central sector of conspicuous N-S-trending anomalies, a heterogeneous western sector of short-wavelength, high-intensity anomalies, and an eastern sector of low- to moderate-intensity broad-wavelength anomalies. Anomalies in the western and central sectors correlate with Neoproterozoic metavolcanic, metasedimentary, and intrusive rocks of the Arabian shield and are interpreted as delineating extensions of shield-type rocks down-dip beneath Phanerozoic cover. These rocks constitute terranes making up part of a Neoproterozoic orogenic belt that underlies Northeast Africa and western Arabia and it is proposed that their magnetically indicated easternmost extent marks the concealed eastern edge of the orogenic belt in central Arabia. The flat magnetic signature of the eastern sector, not entirely accounted for as an effect of deep burial, may reflect the presence of a crustal block different in character to the terranes of the orogenic belt and, speculatively, may outline a continental block that, according to some tectonic models of the region, collided with the Neoproterozoic terranes and thereby caused their deformation and tectonic accretion.

  1. Uranium distribution in the Variscan Basement of Northeastern Sardinia

    CERN Document Server

    Kaçeli, Xhixha M; Baldoncini, M; Bezzon, G P; Buso, G P; Callegari, I; Casini, L; Cuccuru, S; Fiorentini, G; Guastaldi, E; Mantovani, F; Mou, L; Oggiano, G; Puccini, A; Alvarez, C Rossi; Strati, V; Xhixha, G; Zanon, A


    We present a detailed map of the uranium distribution and its uncertainties in the Variscan Basement of Northeastern Sardinia (VBNS) at a scale 1:100,000. An area of 2100 km2 was investigated by means of 535 data points obtained from laboratory and in situ gamma-ray spectrometry measurements. These data volume corresponds to the highest sampling density of the European Variscides, aimed at studying the genetic processes of the upper crust potentially triggered by an enrichment of radiogenic heat-producing elements. For the first time the Kriging with Variance of Measurement Error method was used to assign weights to the input data which are based on the degree of confidence associated to the measurements obtained with different gamma-ray spectrometry techniques. A detailed tuning of the model parameters for the adopted Experimental Semi-Variogram led to identify a maximum distance of spatial variability coherent to the observed tendency of the experimental data. We demonstrate that the obtained uranium distri...

  2. Approaching Biomarkers of Membranous Nephropathy from a Murine Model to Human Disease

    Directory of Open Access Journals (Sweden)

    Chia-Chao Wu


    Full Text Available Background. Membranous glomerulonephropathy (MN is the most prevalent cause of nephrotic syndrome in adult humans. However, the specific biomarkers of MN have not been fully elucidated. We examined the alterations in gene expression associated with the development of MN. Methods. Murine MN was induced by cationic bovine serum albumin (cBSA. After full-blown MN, cDNA microarray analysis was performed to identify gene expression changes, and highly expressed genes were evaluated as markers both in mice and human kidney samples. Results. MN mice revealed clinical proteinuria and the characteristic diffuse thickening of the glomerular basement membrane. There were 175 genes with significantly different expressions in the MN kidneys compared with the normal kidneys. Four genes, metallothionein-1 (Mt1, cathepsin D (CtsD, lymphocyte 6 antigen complex (Ly6, and laminin receptor-1 (Lamr1, were chosen and quantified. Mt1 was detected mainly in tubules, Lamr1 was highly expressed in glomeruli, and CtsD was detected both in tubules and glomeruli. The high expressions of Lamr1 and CtsD were also confirmed in human kidney biopsies. Conclusion. The murine MN model resembled the clinical and pathological features of human MN and may provide a tool for investigating MN. Applying cDNA microarray analysis may help to identify biomarkers for human MN.

  3. Laminin production by human endometrial stromal cells relates to the cyclic and pathologic state of the endometrium

    DEFF Research Database (Denmark)

    Faber, M; Wewer, U M; Berthelsen, J G


    hyperplasia and adenocarcinomas did not react with antibody to laminin. The expression of laminin receptor in the stromal cells codistributed with laminin. Basement membranes of the surface epithelium, the glandular epithelium, and the vessels stained strongly with antibodies to laminin. In preneoplastic...

  4. The basement complexes in Italy, with special regards to those exposed in the Alps: a review

    Institute of Scientific and Technical Information of China (English)

    AttilioBoriani; FrancescoSassi; RaffaeleSassi


    Most of the sedimentary rocks occurring in Italy are post-Carboniferous. All what lies below is considered basement, mostly metamorphic or igneous. Understand-ing the pre-Carboniferous evolution depends on the reconstruction of the sedimentary, metamorphic and igneous evolution of the basement. In general, the base-ment sedimentary protoliths were Lower to Middle Pale-ozoic siliciclastic rocks, while the igneous protolithsbelong to an Ordovician cycle. The prevailing metamor-phism,from very-low grade to granulite facies, is Variscan. It was followed by the formation of large amounts of granitic melts.

  5. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis. (United States)

    Herrera, Cristina; Macêdo, Jéssica Kele A; Feoli, Andrés; Escalante, Teresa; Rucavado, Alexandra; Gutiérrez, José María; Fox, Jay W


    The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM) and other extracellular matrix (ECM) proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs) or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

  6. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

    Directory of Open Access Journals (Sweden)

    Cristina Herrera


    Full Text Available The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM and other extracellular matrix (ECM proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

  7. ew Breakthrough in Research of Framework and Faults in Basement of Turfan Sag

    Institute of Scientific and Technical Information of China (English)

    WangCaifu; HaoHongjian; ChenXiuru


    The deep information of the Turfan sag was extracted and analyzed through the re-processing of the magneto-gravitational data of the Turfan sag in the Turfan-Hami basin. It is considered that the basement faults have played an important role in the controlling of the framework, lithology and the distribution of volcanic rocks in the basement of the Turfan sag. The deep crystalline basement and the upper Hercynian folded basement were studied part by part in the sag through the combined data of aeromagnetic and electric methods. It is revealed that the Huoyanshan fault is steep in the upper and lower parts but gentle in the middle, displaying a “S” type texture, and discovered that there are at least a row of local structures in the down-thrown block of the Huoyanshan fault, through the CEMP prospecting in Huoyanshan. The result is very important for the studying of the Turfan sag as a whole.

  8. Basement configuration of Visakhapatnam - Paradip continental margin from inversion of magnetic anomalies

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, M.M.M.; Rao, S.J.; Venkateswarlu, K.; Murthy, K.S.R.; Murthy, I.V.R.; Subrahmanyam, A.S.

    Inversion of magnetic data was carried out on 40 profiles collected across the continental margin of Visakhapatnam, Andhra Pradesh, India at a spacing of about 10 km and magnetic basement map for this region is prepared. The map reveals complex...

  9. Eponyms in forensic pathology. (United States)

    Nečas, Pavel; Hejna, Petr


    The phenomenon of eponymous terms in forensic pathology is described in this paper. The authors analyzed representative textbooks (monographs) dealing with forensic pathology in both English and German and identified several eponymous terms. The paper aims to present to the reader the most important eponymous terms in forensic pathology. Included in the paper are the following terms: Beckwith's Sign, Casper's Rule, Krönlein's Shot, Lichtenberg's Figures, Nysten's Law, Paltauf's Spots, Puppe's Rule, Sehrt's Sign, Simon's Sign, Sveshnikov's Sign, Tardieu's Spots, Wischnewski Spots, Wydler's Sign. The spread of eponymous terms throughout various languages is mentioned. The linguistic basis of such terms as well as their advantages and disadvantages in specialist fields, and indeed in even wider circles, is discussed. The authors state that the main function of these terms is to facilitate the open flow of unambiguous information among scholars. Eponymous terms in forensic pathology are characteristic for the German speaking countries and for all countries influenced by the German school of forensic pathology. Their usage in the Anglo-Saxon world is much less widespread, meaning they do not occur very often in English monographs and textbooks.

  10. Gravity anomalies and basement structure in Osaka plain; Osaka heiya no juryoku ijo to kiban kozo

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, N.; Nakagawa, K. [Osaka City University, Osaka (Japan). Faculty of Science; Ryoki, K. [Osaka Polytechnical College, Osaka (Japan)


    Many kinds of new information about the underground structure are necessary for elucidating problems on the distribution characteristics of the structural damage and the ground failure due to the 1995 Hyogo-ken Nanbu Earthquake. The gravity anomalies in and around the Osaka sedimentary basin, which is mainly composed of Mesozoic granitic basement and post Tertiary sedimentary layers covering the basement, has been compiled with the data additional gravity measurements in the Hanshin-Osaka area. Basement configuration plays the important role in concentration or dispersion of seismic waves. In general, trends of the gravity anomalies should be removed from obtained gravity anomalies in order to estimate the sub-surface structures. The local free-air anomalies, which are residual anomalies obtained by applying regression technique to regional trends, exhibit linear relationship with the depth to the basement surface. In this study, therefore, the underground structure of the Osaka basin was estimated from the local free-air anomalies. First approximate model of basement surface was constructed by means of the method mentioned above, based upon the two layer (basement rock and the sedimentary cover) model. Further three dimensional model was developed based on the characteristic distribution of density inferred from seismic exploration analysis. 19 refs., 21 figs., 1 tab.

  11. Basement Kind Effects on Air Temperature of a Solar Chimney in Baghdad - Iraq Weather

    Directory of Open Access Journals (Sweden)

    Miqdam Tariq Chaichan


    Full Text Available A solar updraft tower power plant (solar tower is a solar thermal power plant that utilizes a combination of solar air collector and central updraft tube to generate an induced convective flow which drives pressure staged turbines to generate electricity. This paper presents practical results of a prototype of a solar chimney with thermal mass, where the glass surface is replaced by transparence plastic cover. The study focused on chimney's basements kind effect on collected air temperatures. Three basements were used: concrete, black concrete and black pebbles basements. The study was conducted in Baghdad from August to November 2009. The results show that the best chimney efficiency attained was 49.7% for pebbles base. The highest collected air temperature reached was 49ºC when using the black pebbles basement also.also, the maximum basement temperature measured was 59ºC for black pebbles. High increaments in collected air temperatures were achieved in comparison with the ambient air temperatures for the three basement kinds. The highest temperature difference reached was 22ºC with the pebble ground.

  12. Pathological Gambling: Psychiatric Models (United States)

    Westphal, James R.


    Three psychiatric conceptual models: addictive, obsessive-compulsive spectrum and mood spectrum disorder have been proposed for pathological gambling. The objectives of this paper are to (1) evaluate the evidence base from the most recent reviews of each model, (2) update the evidence through 2007 and (3) summarize the status of the evidence for…

  13. Next-Generation Pathology. (United States)

    Caie, Peter D; Harrison, David J


    The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

  14. Pathological Gambling Subtypes (United States)

    Vachon, David D.; Bagby, R. Michael


    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  15. Immunoglobulin V-H-gene usage of autoantibodies in mercuric chloride-induced membranous glomerulopathy in the rat

    NARCIS (Netherlands)

    Dammers, PM; Bun, JCAM; Bellon, B; Kroese, FGM; Aten, J; Bos, NA


    Brown-Norway (BN) and Dorus Zadel Black (DZB) rats develop a T-cell-dependent membranous glomerulopathy (MGP) with high proteinuria and antiglomerular basement membrane (GBM) autoreactive antibodies (Abs), upon exposure to mercuric chloride (HgCl2). Laminin is an important autoantigenic target of th

  16. Upgrading Basements for Combined Nuclear Weapons Effects: Expedient Options (United States)


    joists: for slab and joists 84, sprinklers 1, and asphalt wearing course and membrane 14. * 1977 97 1161 -O"--- II I i i c I U’ i i i I . i" teriel, particularly stud -and-plastbrboard interior walls, to 10.7 psi (closed). The first two require considerable upgrading work; the last...worth- while; and 2 or 3 psi (open), representing the missile hazards of ma- teriel, particularly stud -and-plasterboard interior walls, to 10.7 psi

  17. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin


    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  18. Biobased Membrane

    NARCIS (Netherlands)

    Koenders, E.A.B.; Zlopasa, J.; Picken, S.J.


    The present invention is in the field of a composition for forming a bio-compatible membrane applicable to building material, such as concrete, cement, etc., to a meth od of applying said composition for forming a bio-compatible membrane, a biocompatible membrane, use of said membrane for various pu

  19. Late-Paleozoic emplacement and Meso-Cenozoic reactivation of the southern Kazakhstan granitoid basement (United States)

    De Pelsmaeker, Elien; Glorie, Stijn; Buslov, Mikhail M.; Zhimulev, Fedor I.; Poujol, Marc; Korobkin, Valeriy V.; Vanhaecke, Frank; Vetrov, Evgeny V.; De Grave, Johan


    The Ili-Balkhash Basin in southeastern Kazakhstan is located at the junction of the actively deforming mountain ranges of western Junggar and the Tien Shan, and is therefore part of the southwestern Central Asian Orogenic Belt. The basement of the Ili-Balkhash area consists of an assemblage of mainly Precambrian microcontinental fragments, magmatic arcs and accretionary complexes. Eight magmatic basement samples (granitoids and tuffs) from the Ili-Balkhash area were dated with zircon U-Pb LA-ICP-MS and yield Carboniferous to late Permian (~ 350-260 Ma) crystallization ages. These ages are interpreted as reflecting the transition from subduction to (post-) collisional magmatism, related to the closure of the Junggar-Balkhash Ocean during the Carboniferous-early Permian and hence, to the final late Paleozoic accretion history of the ancestral Central Asian Orogenic Belt. Apatite fission track (AFT) dating of 14 basement samples (gneiss, granitoids and volcanic tuffs) mainly provides Cretaceous cooling ages. Thermal history modeling based on the AFT data reveals that several intracontinental tectonic reactivation episodes affected the studied basement during the late Mesozoic and Cenozoic. Late Mesozoic reactivation and associated basement exhumation is interpreted as distant effects of the Cimmerian collisions at the southern Eurasian margin and possibly of the Mongol-Okhotsk Orogeny in SE Siberia during the Jurassic-Cretaceous. Following tectonic stability during the Paleogene, inherited basement structures were reactivated during the Neogene (constrained by Miocene AFT ages of ~ 17-10 Ma). This late Cenozoic reactivation is interpreted as the far-field response of the India-Eurasia collision and reflects the onset of modern mountain building and denudation in southeast Kazakhstan, which seems to be at least partially controlled by the inherited basement architecture.

  20. A Preliminary Analysis of Relations Between Tectonic Deformation of Sedimentary Cover and Basement in Kuqa Depression

    Institute of Scientific and Technical Information of China (English)

    Liu Jie; Qu Guosheng; Tong Xiaoguang; Song Huizhen; Zhou Qing; Zhang Ning


    Study of seismic activity in the Kuqa area enables us to infer some possible active faults in basement from the ePicentral distribution on different profiles. The relations between active faults in the basement and surface structures are analyzed and the difference between sedimentary cover and basement in their deformation characteristics and the genesis are discussed. The following conclusions have been drawn: (1) the epicentral distribution indicates that, the east Qiulitag and south and north Qiulitag deep faults in the basement correspond to the east and west Qiulitag anticlines, respectively. Moreover, deep faults also exist beneath the Yiqiklik and Yaken anticlines. It indicates that the formation of surface structures is controlled by deep structures; (2) A NE-trending strike-slip fault develops along the line from the western termination of Yiqiklik structure to Dongqiu Well 5 and a NW-trending active fault on the western side of Baicheng. The two active faults across the tectonic strike are the main causes for tectonic segmentation of the Kuqa depression and possibly the cause for the middle segment (Kuqa-Baicheng) of the depression to be more shortened than both its eastern and western terminations; (3) The difference between the sedimentary cover and basement in their deformation characteristics depends mainly on the different properties of media between them.The lithospheric strength of the basement in the basin is fairly high, which determines the basement deformation to be mainly of brittle fracture seismic activity. While the strength of sedimentary cover is low, where there exist weak thin layers, such as coal and gyps. Under the effect of strong tectonic compression, the sedimentary rocks may undergo strong viscous or plastic flow deformation; meanwhile, an aseismic detachment may take place along the weak layers.

  1. [Amniotic membrane in conjunctivoplasty]. (United States)

    Samoila, O; Lacramioara, Totu; Mihu, D


    The basic principles of conjunctival reconstruction are similar in all pathologies that inflict conjunctival tissue loss. Large conjunctival defects are difficult to treat, with little conjunctival reserve that can be used to close the defect. The study had the objective to find alternatives to conjunctival autograft. Frozen amniotic membrane was investigated. From 27 cases, 22 cases were reconstructed using amniotic membrane alone, but in 5 cases conjunctival autograft was also needed. Bulbar conjunctiva was reconstructed in 23 cases, of which 19 with pterygium, 3 with conjunctival tumors, one operatory plague. Fornix reconstruction was carried out in 4 cases, one tumor and 3 symblepharons (2 after conjunctival burns and one pemfigus). The rate of pterygium recurrence was 7,14%. Amniotic membrane can heal large defects of the conjunctiva, either bulbar or forniceal.

  2. Pathology informatics fellowship training: Focus on molecular pathology

    Directory of Open Access Journals (Sweden)

    Diana Mandelker


    Full Text Available Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program′s core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

  3. Fracture and vein characterization of a crystalline basement reservoir, central Yemen (United States)

    Veeningen, R.; Grasemann, B.; Decker, K.; Bischoff, R.; Rice, A. H. N.


    The country of Yemen is located in the south-western part of the Arabian plate. The Pan-African basement found in western and central Yemen is highly deformed during the Proterozoic eon and is part of the Arabian-Nubian shield ANS (670-540Ma). This ANS is a result of the amalgamation of high-grade gneiss terranes and low-grade island arcs. The development of an extensive horst-and-graben system related to the breakup of Gondwana in the Mesozoic, has reactivated the Pan-African basement along NW-SE trending normal faults. As a result, younger Meosozoic marls, sandstones, clastics and limestones are unconformably overlying the basement. Some of these formations act as a source and/or reservoir for hydrocarbons. Due to fracturing of the basement, hydrocarbons have migrated horizontally into the basement, causing the crystalline basement to be a potential hydrocarbon reservoir. Unfortunately, little is known about the Pan-African basement in Central Yemen and due its potential as a reservoir, the deformation and oil migration history (with a main focus on the fracturing and veining history) of the basement is investigated in high detail. Representative samples are taken from 2 different wells from the Habban Field reservoir, located approximately 320 ESE of Sana'a. These samples are analysed using e.g. the Optical Microscope, SEM, EDX and CL, but also by doing Rb-Sr age dating, isotope analysis and fluid inclusion analysis. In well 1, the only lithology present is an altered gneiss with relative large (<5 cm diameter) multi-mineralic veins. In well 3, quartzite (top), gneiss (middle) and quartz porphyry's (middle) are intruded by a so called "younger" granitoid body (592.6±4.1Ma). All lithologies record polyphase systems of mineral veins. Pyrite and saddle dolomite in these veins have euhedral shapes, which means that they have grown in open cavities. Calcite is the youngest mineral in these veins, closing the vein and aborting the fluid flow. Fluid inclusions inside

  4. Feline oral pathology


    Costa, S.; Pais, B.; Almeida, D.; Simões, J.; Mega, A. C.; Vala, Helena


    The main pathologies of the oral cavity are of utmost importance, not only by the number of exposed individuals, but also by the consequences which stems. With the development of this work, we intend to conduct a brief approach to the same, since, specifically affecting domestic felines. Feline Lymphoplasmatic Gingivostomatitis (GELF), the Feline Odontoclastic Reabsorption Lesions (LROF) Complex and gingivitis-stomatitis-pharyngitis, have been studied, some of which are considered an enigma i...

  5. Masochism and pathological gambling. (United States)

    Rosenthal, Richard J


    That all pathological gamblers have an "unconscious wish to lose," an idea first expressed by Freud and Bergler, is neither true nor useful; wrong as well, however, are the reasons for neglecting masochism in relation to gambling. There is a small but clinically significant subgroup of pathological gamblers who are masochistic. I present clinical vignettes and a more extended treatment account to illustrate its importance. Masochism has been a confusing concept. As used here it refers to the deliberate seeking of pain, loss, suffering, or humiliation. There may be pleasure in pain, or an obligatory combining of pleasure and pain. A sense of power and control may be achieved through suffering. The case material illustrates clinically useful types (sexual masochism, masochistic personality disorder, moral masochism, relational masochism) as well as some common masochistic dynamics encountered in the treatment of pathological gamblers. These masochistic patterns are often identifiable during the initial evaluation. Distinguishing features may include a reversal of normal attitudes about winning and losing, the absence of an early winning phase, sometimes a memorable early loss. Gamblers may sabotage opportunities for success or create unnecessary obstacles for themselves. Losing may be more comfortable than winning or may be overtly sexualized.

  6. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, MAJ; Thom, M; Ellison, DW; Wilkins, P; Barnes, D; Thompson, PD; Brown, P


    Objective To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  7. Seismic transpressive basement faults and monocline development in a foreland basin (Eastern Guadalquivir, SE Spain) (United States)

    Pedrera, A.; Ruiz-Constán, A.; Marín-Lechado, C.; Galindo-Zaldívar, J.; González, A.; Peláez, J. A.


    We examine the late Tortonian to present-day deformation of an active seismic sector of the eastern Iberian foreland basement of the Betic Cordillera, in southern Spain. Transpressive faults affecting Paleozoic basement offset up to Triassic rocks. Late Triassic clays and evaporites constitute a décollement level decoupling the basement rocks and a ~100 m thick cover of Jurassic carbonates. Monoclines trending NE-SW to ENE-WSW deform the Jurassic cover driven by the propagation of high-angle transpressive right-lateral basement faults. They favor the migration of clays and evaporites toward the propagated fault tip, i.e., the core of the anticline, resulting in fluid overpressure, fluid flow, and precipitation of fibrous gypsum parallel to a vertical σ3. The overall geometry of the studied monoclines, as well as the intense deformation within the clays and evaporites, reproduces three-layer discrete element models entailing a weak middle unit sandwiched between strong layers. Late Tortonian syn-folding sediments recorded the initial stages of the fault-propagation folding. Equivalent unexposed transpressive structures and associated monoclines reactivated under the present-day NW-SE convergence are recognized and analyzed in the Sabiote-Torreperogil region, using seismic reflection, gravity, and borehole data. A seismic series of more than 2100 low-magnitude earthquakes was recorded within a very limited area of the basement of this sector from October 2012 to May 2013. Seismic activity within a major NE-SW trending transpressive basement fault plane stimulated rupture along a subsidiary E-W (~N95°E) strike-slip relay fault. The biggest event (mbLg 3.9, MW 3.7) occurred at the junction between them in a transpressive relay sector.

  8. Pathology Gross Photography: The Beginning of Digital Pathology. (United States)

    Rampy, B Alan; Glassy, Eric F


    The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale.

  9. Magnetic studies of basement off the coast of Bombay, West of India

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, D.G.

    -WSW directions. Correlations of the anomaly signatures with the geology known from the drill well logs and seismic results infer: (1) the mostly basaltic nature of the basement overlain by the Tertiary sediments, except in the Murud Depression and isolated... with the structural highs and depressions. Two-dimensional model and spectral studies of the anomalies under numerical constraints have revealed the structure of the basement overlain by 1.5-5.0 km thick sediments. A crustal section along a transect across the inner...

  10. Analogue experiments of salt flow and pillow growth due basement faulting and differential loading (United States)

    Warsitzka, M.; Kley, J.; Kukowski, N.


    Basement faulting is widely acknowledged as a potential trigger for salt flow and the growth of salt structures in salt-bearing extensional basins. In this study, dynamically scaled analogue experiments were designed to examine the evolution of salt pillows and the kinematics of salt flow due to a short pulse of basement faulting and a long-lasting phase of successive sedimentation. Experiments performed in the framework of this study consist of viscous silicone putty to simulate ductile rock salt, and a PVC-beads-quartz sand mixture representing a brittle supra-salt layer. In order to derive 2-D incremental displacement and strain patterns, the analogue experiments were monitored by an optical image correlation system (Particle Imaging Velocimetry). By varying layer thicknesses and extension rates, the influence of these parameters on the kinematics of salt flow were tested. Model results reveal that significant strain is triggered in the viscous layer by minor basement faulting. During basement extension downward flow occurs in the viscous layer above the basement fault tip. In contrast, upward flow takes place during post-extensional sedimentation. Lateral redistribution of the viscous material during post-extensional sedimentation is associated with subsidence above the footwall block and uplift adjacent to the basement faults leading to the formation of pillow structures (primary pillows). Decoupled cover faulting and the subsidence of peripheral sinks adjacent to the primary pillow causes the formation of additional pillow structures at large distance from the basement fault (secondary pillows). Experimental results demonstrate that the development of salt pillows can be triggered by basement extension, but requires a phase of tectonic quiescence. The potential for pillow growth and the displacement rate in the viscous layer increase with increasing thickness of the viscous layer and increasing extension rate, but decrease with increasing thickness of the

  11. Zircon U-Pb ages of the basement rocks beneath the Songliao Basin, NE China

    Institute of Scientific and Technical Information of China (English)


    The basement of the Songliao Basin is mainly composed of slightly-metamorphosed or unmetamorphosed Paleozoic strata, granites and gneiss. Petrographical studies indicate that the gneiss was originally the granitic intrusions which were deformed in the later stage. One undeformed granitic rock sample gives a U-Pb age of (305±2) Ma, and the mylonitic granite yields a U-Pb age of (165±3) Ma. Both of the two samples contain no inherited zircon, which suggests that there is no large-scale Precambrian crystalline basement beneath the Songliao Basin.

  12. Analogue experiments of salt flow and pillow growth due to basement faulting and differential loading (United States)

    Warsitzka, M.; Kley, J.; Kukowski, N.


    Salt flow in sedimentary basins is mainly driven by differential loading and can be described by the concept of hydraulic head. A hydraulic head in the salt layer can be imposed by vertically displacing the salt layer (elevation head) or the weight of overburden sediments (pressure head). Basement faulting in salt-bearing extensional basins is widely acknowledged as a potential trigger for hydraulic heads and the growth of salt structures. In this study, scaled analogue experiments were designed to examine the kinematics of salt flow during the early evolution of a salt structure triggered by basement extension. In order to distinguish flow patterns driven by elevation head or by pressure head, we applied a short pulse of basement extension, which was followed by a long-lasting phase of sedimentation. During the experiments viscous silicone putty simulated ductile rock salt, and a PVC-beads/quartz-sand mixture was used to simulate a brittle supra-salt layer. In order to derive 2-D incremental displacement and strain patterns, the analogue experiments were monitored using an optical image correlation system (particle imaging velocimetry). By varying layer thicknesses and extension rates, the influence of these parameters on the kinematics of salt flow were tested. Model results reveal that significant flow can be triggered in the viscous layer by small-offset basement faulting. During basement extension downward flow occurs in the viscous layer above the basement fault tip. In contrast, upward flow takes place during post-extensional sediment accumulation. Flow patterns in the viscous material are characterized by channelized Poiseuille-type flow, which is associated with subsidence in regions of "salt" expulsion and surface uplift in regions of inflation of the viscous material. Inflation of the viscous material eventually leads to the formation of pillow structures adjacent to the basement faults (primary pillows). The subsidence of peripheral sinks adjacent to

  13. Membranous nephropathy (United States)

    ... page: // Membranous nephropathy To use the sharing features on this page, please enable JavaScript. Membranous nephropathy is a kidney disorder that leads to changes ...

  14. Firing membranes

    NARCIS (Netherlands)

    Kappert, Emiel Jan


    Thermal processing is commonly employed to alter the chemistry and microstructure of membrane layers. It can shape, strengthen, and give functionality to a membrane. A good understanding of the processes taking place during the thermal processing of a membrane material allows for optimization and tu

  15. Resistivity soundings and VLF profiles for siting groundwater wells in a fractured basement aquifer in the Arabian Shield, Saudi Arabia (United States)

    Ammar, A. I.; Kruse, S. E.


    Seasonal shortages of groundwater are common in parts of the Arabian Shield, where complex basement hydrogeology can make siting of water wells difficult. To identify optimal production well locations, six 200-400 m-long Very Low Frequency (VLF) electromagnetic traverses and ten Vertical Electrical Soundings (VESes) were run at the western edge of the Arabian Shield near At-Taif town, Saudi Arabia. Here wadi sediments overlie fractured Precambrian basement, which in turn overlies unfractured basement. The fractured basement forms the water supply aquifer. Both VLF and VES data indicate significant lateral heterogeneity in the electrical conductivity of both wadi and basement deposits over lengths scales as small as ∼100 m. VES results correlate closely with data from two wells in the study area. The change in resistivity at the wadi-to-fractured basement contact is relatively subtle, but the transition from low resistivity fractured basement to high resistivity unfractured basement is well resolved. Inferred wadi thicknesses range from 0 to 14 m; the electrically conductive fractured basement extends from wadi down to 12-32 m depth. VES data indicate the fractured basement aquifer thickens progressively to the south in this area. A production well, sited on the basis of the VES analysis, successfully yielded 70m3/day. The relationship between VLF and VES data is complex, suggesting that the terrain is heterogeneous on the scale of the different effective sampling volumes of the two methods, and/or that fracture azimuth is locally heterogeneous. Overall resistivities in this study are similar to those observed at other locations in Saudi Arabia, suggesting these methods may be widely applicable for siting of groundwater wells in the complex basement of the Arabian Shield.

  16. Pathology of the vestibulocochlear nerve

    Energy Technology Data Exchange (ETDEWEB)

    De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail:; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail:


    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  17. [(Impending) pathological fracture]. (United States)

    Sutter, P M; Regazzoni, P


    Pathological fractures will be encountered in increasing frequency due to more patients with cancer, surviving a longer period. The skeleton is the third most frequent localization for metastases. Breast cancer is still the most common primary tumor, but bone metastases from lung cancer seem to be diagnosed more and more. Despite of finding metastases most often in the spinal column, fractures are seen mostly at the femoral site. A pathological fracture and, in almost all cases, an impending fracture are absolute indication for operation. An exact definition of an "impending fracture" is still lacking; it is widely accepted, that 50 per cent of bone mass must be destroyed before visualization in X-ray is possible, thus defining an impending fracture. The score system by Mirels estimates the fracture risk by means of four parameters (localization, per cent of destructed bone mass, type of metastasis, pain). Improving quality of life, relieving pain, preferably with a single operation and a short length of stay are the goals of (operative) treatment. For fractures of the proximal femur, prosthetic replacement, for fractures of the subtrochanteric region or the shaft, intramedullary nails are recommended. Postoperative radiation therapy possibly avoids tumor progression. In patient with a good long term prognosis, tumor should be removed locally aggressive.

  18. Pathology of intrahepatic cholangiocarcinoma (United States)

    Vijgen, Sandrine; Terris, Benoit


    Intrahepatic cholangiocarcinoma (iCC) is a primary carcinoma of the liver with increasing significance and major pathogenic, clinical and therapeutic challenges. Classically, it arises from malignant transformation of cholangiocytes bordering small portal bile duct (BD) to second-order segmental large BDs. It has three major macroscopic growth pattern [mass-forming (MF), periductal infiltrative (PI), and intraductal growth (IG)] and histologically is a desmoplastic stroma-rich adenocarcinoma with cholangiocyte differentiation. Recent data pointed out noteworthy degree of heterogeneity in regards of their epidemiology and risk factors, pathological and molecular features, pathogenesis, clinical behaviors and treatment. Notably, several histological variants are described and can coexist within the same tumor. Several different cells of origin have also been depicted in a fraction of iCCs, amongst which malignant transformation of ductules, of hepatic stem/progenitor cells, of periductal glands or through oncogenic reprogramming of adult hepatocytes. A degree of pathological overlap with hepatocellular carcinoma (HCC) may be observed in a portion of iCC. A series of precursor lesions are today characterized and emphasize the existence of a multistep carcinogenesis process. Overall, these new data have brought up in proposal of new histological or molecular classifications, which could soon replace current anatomic-based classification and could have major impact on establishment of prognosis and on development of novel target treatment approaches. PMID:28261592

  19. Membrane Biophysics

    CERN Document Server

    Ashrafuzzaman, Mohammad


    Physics, mathematics and chemistry all play a vital role in understanding the true nature and functioning of biological membranes, key elements of living processes. Besides simple spectroscopic observations and electrical measurements of membranes we address in this book the phenomena of coexistence and independent existence of different membrane components using various theoretical approaches. This treatment will be helpful for readers who want to understand biological processes by applying both simple observations and fundamental scientific analysis. It provides a deep understanding of the causes and effects of processes inside membranes, and will thus eventually open new doors for high-level pharmaceutical approaches towards fighting membrane- and cell-related diseases.

  20. Pathological conditions associated with rhinitis medicamentosa

    Directory of Open Access Journals (Sweden)

    Milošević Dušanka


    Full Text Available Rhinitis medicamentosa (nose-drop-nose" is a term used for pathological condition of the nasal mucous membrane that results from long-term abuse with intranasal vasoconstrictors. The aim of this work was to examine what lead the patients with nosedropnose rhinitis to the initial usage of intranasal vasoactive drugs, in this prospective study, 92 patients with rhinitis medicamentosa were included. The evaluation of all study subjects comprised the history, ORL, microbiological and radiological examination, skin prick tests with a battery of routine respiratory and nutritive allergens and nasal cytology. The results of this study showed that the pathological conditions for initial use of intranasal vasoactive drugs were: acute upper respiratory infections in 293%, vasomotor rhinitis in 21.7%, allergic rhinitis in 16.3%, deviated nasal septum in 13.0%, nasal polyposis in 12%, rhinitis induced by mechanical trauma in 4.4%, and hormonal rhinitis in 3.3% of patients with rhinitis medicamentosa. In conclusion, the most common pathological conditions for developing rhinitis medicamentosa were chronic inflammatory and structural diseases manifested by permanent nasal obstruction as well as acute upper respiratory infections are.

  1. Pathological study on severe acute respiratory syndrome

    Institute of Scientific and Technical Information of China (English)

    郎振为; 张立洁; 张世杰; 孟忻; 李俊强; 宋晨朝; 孙琳; 周育森


    Objective To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation. Methods Tissue specimens from 3 autopsies of probable SARS cases were studied by microscope, and the clinical data was reviewed.Results The typical pathological changes of lungs were diffuse hemorrhaging on the surface. A combination of serous, fibrinous and hemorrhagic inflammation was seen in most of the pulmonary alveoli with the engorgement of capillaries and detection of micro-thrombosis in some of these capillaries. Pulmonary alveoli thickened with interstitial mononuclear inflammatory infiltrates, suffered diffuse alveolar damage, experienced desquamation of pneumocytes and had hyaline-membrane formation, fibrinoid materials, and erythrocytes in alveolar spaces. There were thromboembolisms in some bronchial arteries. Furthermore, hemorrhagic necrosis was also evident in lymph nodes and spleen with the attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and lesions having existed before hospitalization were observed in the liver, heart, kidney and pancreas.Conclusion Severe damage to the pulmonary and immunological systems is responsible for the clinical features of SARS and may lead to the death of patients.

  2. Clinical and experimental pathology of Moyamoya disease

    Institute of Scientific and Technical Information of China (English)

    饶明俐; 张海鸥; 刘群; 张淑琴; 胡林森; 邓方


    Objective To investigate the etiology, pathology, and mechanism of pathogenesis of Moyamoya disease.Methods A total of 15 human autopsies were analyzed. In addition, in order to create an animal model of the disease, 21 Japanese rabbits were divided randomly into two groups and subjected to injections of horse serum either intravenously or locally in the area of the sympathetic ganglia. Pathological and immunohistochemical characteristics were observed.Results The pathological features of the autopsies and the animal models both involved intima hyperplasia and stenosis or even occlusion of the lumen in the terminal ends of the internal carotid artery and the anterior and middle cerebral arteries. Disconnections or even breakages of the inner layer of the lumen were also observed, without an obvious inflammatory response. Hyperplasic smooth muscle cells of the medial membrane had extended inward through broken portions of the internal elastic lamina, with intima cell hyperplasia resulting in lumen stenosis. The hyperplastic vascular walls were positive for IgG and IgM.Conclusions The etiology of Moyamoya disease may involve allergic angiitis. A possible mechanism is that proximal portions of the circle of Willis first develop chronic stenosis or occlusion, leading to compensatory small vessel proliferation, which perforates into the cerebral parenchyma.

  3. Regional trends in radiogenic heat generation in the Precambrian basement of the Western Canadian Basin (United States)

    Jones, F. W.; Majorowicz, J. A.

    Radiogenic heat generation values for 381 basement samples from 229 sites in the western Canadian basin exhibit a lognormal frequency distribution. The mean value = 2.06 (S.D. = 1.22) µWm-3 is larger than the radiogenic heat generation values reported for the shield in the Superior (ca. 1.2 µWm-3, Jessop and Lewis, 1978) and Churchill (ca. 0.7 µWm-3, Drury, 1985) provinces. When equal Log A contour intervals are used to map the basement heat generation, three large zones of relatively high heat generation are found. One coincides with the Peace River Arch basement structure and one with the Athabasca axis (Darnley, 1981). There is no apparent indication of increased heat flow through the Paleozoic formations associated with these two zones. The third zone, in southwestern Saskatchewan, coincides with a high heat flow zone in the Swift Current area. The lack of correlation between heat flow and heat generation in Alberta may be due to the disturbance to the heat flow in the Paleozoic formations by water motion, or may indicate that the heat is from uranium, thorium and potassium isotope enrichment near the basement surface rather than enrichment throughout the entire upper crust.

  4. Groundwater recharge estimation and water resources assessment in a tropical crystalline basement aquifer

    NARCIS (Netherlands)

    Nyagwambo, N.L.


    Groundwater recharge estimation in crystalline basement aquifers in semi-arid tropical areas is best estimated at monthly time scales as this best captures the dynamics of recharge processes in these areas. Whilst it is standard practice to use at least two methods to estimate the recharge it may be

  5. Influence of basement structures on in situ stresses over the Surat Basin, southeast Queensland (United States)

    Brooke-Barnett, Samuel; Flottmann, Thomas; Paul, Pijush K.; Busetti, Seth; Hennings, Peter; Reid, Ray; Rosenbaum, Gideon


    The Jurassic to Cretaceous sedimentary rocks of the Surat Basin in southeast Queensland host a significant volume of coal seam gas resources. Consequently, knowledge of the in situ stress is important for coal permeability enhancement and wellbore stability. Using wireline log data and direct stress measurements, we have calculated stress orientations from 36 wells and stress magnitudes from 7 wells across the Surat Basin. Our results reveal a relationship between high tectonic stress and proximity to structures within the underlying "basement" rocks. The influence of tectonic stresses is diminished with depth in areas with thicker sedimentary cover that are relatively far from the basement structures. We suggest that this relationship is due to the redistribution of in situ stresses around areas where basement is shallower and where basement structures, such as the Leichhardt-Burunga Fault System, are present. This behavior is explained by a lower rigidity in the thickest basin cover, which reduces the ability to maintain higher tectonic stress. Over the entire Surat Basin, a significant amount of variability in in situ stress orientation is observed. The authors attribute this stress variability to complex plate boundary interactions on the northern and eastern margins of the Indo-Australian Plate.

  6. Impact of climate changes during the last 5 million years on groundwater in basement aquifers. (United States)

    Aquilina, Luc; Vergnaud-Ayraud, Virginie; Les Landes, Antoine Armandine; Pauwels, Hélène; Davy, Philippe; Pételet-Giraud, Emmanuelle; Labasque, Thierry; Roques, Clément; Chatton, Eliot; Bour, Olivier; Ben Maamar, Sarah; Dufresne, Alexis; Khaska, Mahmoud; Le Gal La Salle, Corinne; Barbecot, Florent


    Climate change is thought to have major effects on groundwater resources. There is however a limited knowledge of the impacts of past climate changes such as warm or glacial periods on groundwater although marine or glacial fluids may have circulated in basements during these periods. Geochemical investigations of groundwater at shallow depth (80-400 m) in the Armorican basement (western France) revealed three major phases of evolution: (1) Mio-Pliocene transgressions led to marine water introduction in the whole rock porosity through density and then diffusion processes, (2) intensive and rapid recharge after the glacial maximum down to several hundred meters depths, (3) a present-day regime of groundwater circulation limited to shallow depth. This work identifies important constraints regarding the mechanisms responsible for both marine and glacial fluid migrations and their preservation within a basement. It defines the first clear time scales of these processes and thus provides a unique case for understanding the effects of climate changes on hydrogeology in basements. It reveals that glacial water is supplied in significant amounts to deep aquifers even in permafrosted zones. It also emphasizes the vulnerability of modern groundwater hydrosystems to climate change as groundwater active aquifers is restricted to shallow depths.


    Active soil ventilation techniques have been tested in 26 block-wall basement houses in eastern Pennsylvania with significantly elevated indoor radon concentrations, generally above 740 Bq/m3, and the results indicate that radon levels can be reduced substantially often below the...

  8. Impact of climate changes during the last 5 million years on groundwater in basement aquifers (United States)

    Aquilina, Luc; Vergnaud-Ayraud, Virginie; Les Landes, Antoine Armandine; Pauwels, Hélène; Davy, Philippe; Pételet-Giraud, Emmanuelle; Labasque, Thierry; Roques, Clément; Chatton, Eliot; Bour, Olivier; Ben Maamar, Sarah; Dufresne, Alexis; Khaska, Mahmoud; La Salle, Corinne Le Gal; Barbecot, Florent


    Climate change is thought to have major effects on groundwater resources. There is however a limited knowledge of the impacts of past climate changes such as warm or glacial periods on groundwater although marine or glacial fluids may have circulated in basements during these periods. Geochemical investigations of groundwater at shallow depth (80–400 m) in the Armorican basement (western France) revealed three major phases of evolution: (1) Mio-Pliocene transgressions led to marine water introduction in the whole rock porosity through density and then diffusion processes, (2) intensive and rapid recharge after the glacial maximum down to several hundred meters depths, (3) a present-day regime of groundwater circulation limited to shallow depth. This work identifies important constraints regarding the mechanisms responsible for both marine and glacial fluid migrations and their preservation within a basement. It defines the first clear time scales of these processes and thus provides a unique case for understanding the effects of climate changes on hydrogeology in basements. It reveals that glacial water is supplied in significant amounts to deep aquifers even in permafrosted zones. It also emphasizes the vulnerability of modern groundwater hydrosystems to climate change as groundwater active aquifers is restricted to shallow depths. PMID:26392383

  9. Groundwater Recharge Estimation And Water Resources Assessment In A Tropical Crystalline Basement Aquifer

    NARCIS (Netherlands)

    Nyagwambo, N.L.


    While most groundwater recharge estimation methods give reasonable long-term annual average estimates very few if any methods offer guidance on monthly recharge. In crystalline basement aquifers (CBAs) the problem is compounded by the high seasonal, intra-annual and inter-annual variability. The chl

  10. Delineation of Piceance Basin basement structures using multiple source data: Implications for fractured reservoir exploration

    Energy Technology Data Exchange (ETDEWEB)

    Hoak, T.E.; Klawitter, A.L.


    Fractured production trends in Piceance Basin Cretaceous-age Mesaverde Group gas reservoirs are controlled by subsurface structures. Because many of the subsurface structures are controlled by basement fault trends, a new interpretation of basement structure was performed using an integrated interpretation of Landsat Thematic Mapper (TM), side-looking airborne radar (SLAR), high altitude, false color aerial photography, gas and water production data, high-resolution aeromagnetic data, subsurface geologic information, and surficial fracture maps. This new interpretation demonstrates the importance of basement structures on the nucleation and development of overlying structures and associated natural fractures in the hydrocarbon-bearing section. Grand Valley, Parachute, Rulison, Plateau, Shire Gulch, White River Dome, Divide Creek and Wolf Creek fields all produce gas from fractured tight gas sand and coal reservoirs within the Mesaverde Group. Tectonic fracturing involving basement structures is responsible for development of permeability allowing economic production from the reservoirs. In this context, the significance of detecting natural fractures using the intergrated fracture detection technique is critical to developing tight gas resources. Integration of data from widely-available, relatively inexpensive sources such as high-resolution aeromagnetics, remote sensing imagery analysis and regional geologic syntheses provide diagnostic data sets to incorporate into an overall methodology for targeting fractured reservoirs. The ultimate application of this methodology is the development and calibration of a potent exploration tool to predict subsurface fractured reservoirs, and target areas for exploration drilling, and infill and step-out development programs.

  11. On the issue of the Precambrian basement of the Arctic shelf (United States)

    Vernikovsky, Valery A.; Korago, Evgeny A.; Proskurnin, Vasily F.; Sobolev, Nikolay N.


    Many researchers of the geological structures of the Russian Arctic concluded that the basements of the terranes composing the Arctic shelf and continental slopes have a Precambrian age. It is assumed that these terranes are actually fragments of the ancient Arctida paleocontinent [Zonenshain, Natapov, 1987] that broke up as a result of rifting and its separate plates and terranes either were overlain by continental margins sediments or included in the fold belts in the periphery of the ocean. In the western part of the Russian Arctic, a Grenvillian and Mesoproterozoic basement was demonstrated for Svalbard, Novaya Zemlya and Taimyr Peninsula, and at least a Neoproterozoic basement was established for structures in the basement of Severnaya Zemlya archipelago. In the eastern part of the Russian Arctic, such proofs were almost nonexistent. In recent years, new information was obtained concerning the continental nature and Precambrian age of the basement crust of the New Siberian Islands and De Long archipelagos as well as probably the Mendeleev Ridge. For the New Siberian Islands and De Long archipelagos, a whole series of geochronological evidence was obtained in addition to geological data (horizontally bedding Early Paleozoic passive continental margin sediments (Cambrian, Ordovician) at Bennett Island). In magmatic and tuffaceous-sedimentary rocks of Henrietta and Zhokhov islands we discovered zircons that had formed from magmatic crystallization in the Late Neoproterozoic. New U-Pb data for zircons from rocks of these islands do not contradict isotopic dating obtained earlier by other methods - Ar/Ar and Sm/Nd in different laboratories. Considering different closure temperatures for isotopic systems, these new results complement each other. On the islands of the eastern sector of the Russian Arctic, a Neoproterozoic complex of rocks is most certainly established in the basement of the mesozoides of Vrangel Island. Here were discovered metamorphosed volcanics

  12. Radiolytic hydrogen production in basaltic basement of the South Pacific Gyre (United States)

    Dzaugis, M. E.; Spivack, A. J.; Dunlea, A. G.; Murray, R. W.; Kelley, K. A.; D'Hondt, S. L.


    Water radiolysis is the decomposition of water molecules due to interactions with ionizing radiation from the natural decay of radioactive elements, such as uranium (238U, 235U), thorium (232Th) and potassium (40K). This abiotic process produces electron donors (e.g., H2) and acceptors (e.g., O2) that microorganisms can metabolize for energy. Although water radiolysis has been examined in deep continental crust (Lin et al., 2005) and marine sediment (Blair et al., 2007), it has not been rigorously addressed in oceanic basement. The submarine depth to which life extends on Earth, and the potential for life in basaltic aquifers of other worlds (such as Mars and Europa), may depend on radiolytic production of electron donors and acceptors. In order to quantify the extent to which water radiolysis occurs in the subseafloor basaltic basement, we (i) quantified radioactive element concentrations of basement samples from Integrated Ocean Drilling Program (IODP) Expedition 329 and (ii) developed a quantitative model of H2 production by water radiolysis in the basement aquifer. Modeling radiolytic production of H2 in oceanic basement is difficult because the basement is a heterogeneous environment. Microscale changes in physical properties and chemical composition cause microscale variation in water radiolysis within the basement. During radioactive decay, alpha particles, beta particles and gamma rays are emitted, each with a spectrum of characteristic energies. The distance over which radiation is attenuated depends on the kind of radiation (alpha, beta or gamma), initial energy, and the absorbing material. These properties and the concentration of radioactive elements provide the basis for our preliminary model. We are using inductively coupled plasma emission spectroscopy (ICP-ES), mass spectrometry (ICP-MS) and laser ablation (LA ICP-MS) to map variation in radioelement concentrations from phase to phase (e.g., across successive alteration halos to unaltered rock). The

  13. Exploitation of Groundwater in Fractured Basement of Ado-Ekiti, Nigeria

    Directory of Open Access Journals (Sweden)

    Oluwadare Joshua OYEBODE


    Full Text Available Groundwater is the most efficient resource for meeting water demand in the basement complex areas. Basement complexes worldwide shared common hydrogeological indicators and the situation in the entire Ado Ekiti is not like to be far from that of Afe Babalola University Ado-Ekiti, Ekiti State (ABUAD.This study examined groundwater exploitation in fractured basement of Ado Ekiti and environs. The scope was narrowed to groundwater supply and potential in ABUAD. Seventeen boreholes have been drilled in ABUAD and yet there is a seeming perennial water scarcity in the University. The data generated in this study could provide benchmarks to unravel the prevailing conditions on groundwater potential and exploitation in fractured basement in the whole of Ado Ekiti and environs. The study revealed that most appealing geologic sequence for good groundwater potential is overburden thickness of ≥ 25m and weathered/fractured basement having resistivity range between 20 - 100Ω-m with thickness ranging between 12 – 30m. Present daily water demand for ABUAD stands at 420,000litres/day and in a decade’s time the daily projection is expected to be 934200liters/day. If the University is experiencing water scarcity, it means that all the boreholes put altogether is currently producing below 37% efficiency. The problem probably could be attributed to poor borehole completion operation, ‘hanging borehole’ and incomplete development. Pumping test is very vital for successful borehole completion and benchmark for future operation and maintenance. Efforts should be geared towards the redevelopment of all the boreholes in ABUAD to increase their efficiencies. Pumping test should be carried out to ascertain the true status of the remaining boreholes. Efforts should only be concentrated in areas designated to have good groundwater potential for new borehole schemes. As a long term measures and also to meet up with the decade’s forecast on water demand, dam

  14. The timing of metamorphism in the Odenwald-Spessart basement, Mid-German Crystalline Zone (United States)

    Will, T. M.; Schulz, B.; Schmädicke, E.


    New in situ electron microprobe monazite and white mica 40Ar/39Ar step heating ages support the proposition that the Odenwald-Spessart basement, Mid-German Crystalline Zone, consists of at least two distinct crustal terranes that experienced different geological histories prior to their juxtaposition. The monazite ages constrain tectonothermal events at 430 ± 43 Ma, 349 ± 14 Ma, 331 ± 16 Ma and 317 ± 12 Ma/316 ± 4 Ma, and the 40Ar/39Ar analyses provide white mica ages of 322 ± 3 Ma and 324 ± 3 Ma. Granulite-facies metamorphism occurred in the western Odenwald at c. 430 and 349 Ma, and amphibolite-facies metamorphism affected the eastern Odenwald and the central Spessart basements between c. 324 and 316 Ma. We interpret these data to indicate that the Otzberg-Michelbach Fault Zone, which separates the eastern Odenwald-Spessart basement from the Western Odenwald basement, is part of the Rheic Suture, which marks the position of a major Variscan plate boundary separating Gondwana- and Avalonia-derived crustal terranes. The age of the Carboniferous granulite-facies event in the western Odenwald overlaps with the minimum age of eclogite-facies metamorphism in the adjacent eastern Odenwald. The granulite- and eclogite-facies rocks experienced contrasting pressure-temperature paths but occur in close spatial proximity, being separated by the Rheic Suture. As high-pressure and high-temperature metamorphisms are of similar age, we interpret the Odenwald-Spessart basement as a paired metamorphic belt and propose that the adjacent high-pressure and high-temperature rocks were metamorphosed in the same subduction zone system. Juxtaposition of these rocks occurred during the final stages of the Variscan orogeny along the Rheic Suture.

  15. 永存原始玻璃体增生症的临床表现及晶状体后纤维血管膜的病理学特征%Clinical manifestations and pathological characteristics of retrolental membranes secondary to persistent hyperplastic primary vitreous

    Institute of Scientific and Technical Information of China (English)

    张岩; 林锦镛


    Background Persistent hyperplastic primary vitreous (PHPV) is a congenital eye disease of children,because its clinical manifestations are nonspecific,it is easy to be misdiagnosed as congenital cataract and the prognosis is poor.There has been more researches on PHPV clinical characteristics than its histopathological feature and immunochemistry.Objective This study was to investigate the clinical characteristics of PHPV and the pathological characteristics of retrolental membranes secondary to PHPV.Methods The clinical data of 6 PHPV eyes from 6 patients during May 2005 to December 2014 were retrospectively analyzed.All the PHPV eyes received a combinating procedure of cataract extraction and anterior vitrectomy.The retrolental membranes were collected during surgery for the histopathological examination by hematoxylin & eosin staining and periodic acid-Schiff (PAS)staining.Immunochemistry was used to detect the expression of Vimentin,smooth muscle actin (SMA),S-100,glial fibrillary acidic protein (GFAP),neuron specific enolase (NSE),epithelial membrane antigen (EMA),CD34 and proliferating cell nuclear antigen (PCNA) in the retrolental membranes.Results Monocular PHPV was found in 6 cases since born,with the main clinical manifestation of similar to congenital cataract.The ocular axial was shorter in 5 PHPV eyes than that of the contralateral eye by A-sonography,and 1 eye accompanied by eye nystagmus,strabismus and small cornea.The retrolental membranes were seen during the surgery in all cases,and the white band through the vitreous in 2 eyes.Pathological examination showed that the retrolental membrane was mainly composed of loose or myxoid connective tissue fibers,the capillaries and small veins.PAS positive tissue,residual transparent artery and differentiated adipocytes were exhibited in some specimens.Immunohistochemistry indicated that spindle-shape cells in the retrolental membranes presented the characteristics of mesenchymal cells,and some cells

  16. Imaging of oral pathological tissue using optical coherence tomography (United States)

    Canjau, Silvana; Todea, Carmen; Sinescu, Cosmin; Duma, Virgil-Florin; Topala, Florin I.; Podoleanu, Adrian G.


    Oral squamous cell carcinoma (OSCC) constitutes 90% of oral cancer. Early detection is a cornerstone to improve survival. Interaction of light with tissues may highlight changes in tissue structure and metabolism. We propose optical coherence tomography (OCT), as a non-invasive diagnosis method, being a new high-resolution optical technique that permits tri-dimensional (3-D), real-time imaging of near surface abnormalities in complex tissues. In this study half of the excisional biopsy was directed to the pathologist and the other half was assigned for OCT investigation. Histopathology validated the results. Areas of OSCC of the buccal mucosa were identified in the OCT images. The elements obserced included extensive epithelial down-growth, the disruption of the basement membrane, with areas of erosion, an epithelial layer that was highly variable in thickness and invasion into the sub-epithelial layers. Therefore, OCT appears to be a highly promising imaging modality.

  17. Nontraditional applications in clinical pathology. (United States)

    Jordan, Holly L; Register, Thomas C; Tripathi, Niraj K; Bolliger, Anne Provencher; Everds, Nancy; Zelmanovic, David; Poitout, Florence; Bounous, Denise I; Wescott, Debra; Ramaiah, Shashi K


    Most published reviews of preclinical toxicological clinical pathology focus on the fundamental aspects of hematology, clinical chemistry, coagulation, and urinalysis in routine toxicology animal species, for example, rats, mice, dogs, and nonhuman primates. The objective of this continuing education course was to present and discuss contemporary examples of nonroutine applications of clinical pathology endpoints used in the drug development setting. Area experts discussed bone turnover markers of laboratory animal species, clinical pathology of pregnant and growing laboratory animals, clinical pathology of nonroutine laboratory animal species, and unique applications of the Siemens Advia(®) hematology analyzer. This article is a summary based on a presentation given at the 31st Annual Symposium of the Society of Toxicologic Pathology, during the Continuing Education Course titled "Nontraditional Applications of Clinical Pathology in Drug Discovery and Preclinical Toxicology."

  18. Role of mitochondria in parvovirus pathology.

    Directory of Open Access Journals (Sweden)

    Jonna Nykky

    Full Text Available Proper functioning of the mitochondria is crucial for the survival of the cell. Viruses are able to interfere with mitochondrial functions as they infect the host cell. Parvoviruses are known to induce apoptosis in infected cells, but the role of the mitochondria in parvovirus induced cytopathy is only partially known. Here we demonstrate with confocal and electron microscopy that canine parvovirus (CPV associated with the mitochondrial outer membrane from the onset of infection. During viral entry a transient depolarization of the mitochondrial transmembrane potential and increase in ROS level was detected. Subsequently, mitochondrial homeostasis was normalized shortly, as detected by repolarization of the mitochondrial membrane and decrease of ROS. Indeed, activation of cell survival signalling through ERK1/2 cascade was observed early in CPV infected cells. At 12 hours post infection, concurrent with the expression of viral non-structural protein 1, damage to the mitochondrial structure and depolarization of its membrane were apparent. Results of this study provide additional insight of parvovirus pathology and also more general information of virus-mitochondria association.

  19. Role of mitochondria in parvovirus pathology. (United States)

    Nykky, Jonna; Vuento, Matti; Gilbert, Leona


    Proper functioning of the mitochondria is crucial for the survival of the cell. Viruses are able to interfere with mitochondrial functions as they infect the host cell. Parvoviruses are known to induce apoptosis in infected cells, but the role of the mitochondria in parvovirus induced cytopathy is only partially known. Here we demonstrate with confocal and electron microscopy that canine parvovirus (CPV) associated with the mitochondrial outer membrane from the onset of infection. During viral entry a transient depolarization of the mitochondrial transmembrane potential and increase in ROS level was detected. Subsequently, mitochondrial homeostasis was normalized shortly, as detected by repolarization of the mitochondrial membrane and decrease of ROS. Indeed, activation of cell survival signalling through ERK1/2 cascade was observed early in CPV infected cells. At 12 hours post infection, concurrent with the expression of viral non-structural protein 1, damage to the mitochondrial structure and depolarization of its membrane were apparent. Results of this study provide additional insight of parvovirus pathology and also more general information of virus-mitochondria association.

  20. Multicomponent membranes (United States)

    Kulprathipanja, Santi; Kulkarni, Sudhir S.; Funk, Edward W.


    A multicomponent membrane which may be used for separating various components which are present in a fluid feed mixture comprises a mixture of a plasticizer such as a glycol and an organic polymer cast upon a porous organic polymer support. The membrane may be prepared by casting an emulsion or a solution of the plasticizer and polymer on the porous support, evaporating the solvent and recovering the membrane after curing.

  1. [Psychiatric comorbidity in pathological gambling]. (United States)

    Skokauskas, Norbertas; Satkeviciūte, Regina; Burba, Benjaminas


    In this article the peculiarities of psychiatric comorbidity in pathological gambling were investigated. The authors were based both on the data of many foreign scientists and on their own one. Our data on 77 cases of pathological gambling were collected based on interviews of Lithuanian psychiatrists and psychotherapists about their patients with gambling addiction in period from 1991 to 2001. The data that we publish and analyze allows us to make conclusions that pathological gambling can reveal together with very wide spectrum of psychiatric disorders, but more often with alcoholism and depression. The mechanism of psychiatric comorbidity in pathological gambling is very complex.

  2. Recommendations for pathology peer review. (United States)

    Morton, Daniel; Sellers, Rani S; Barale-Thomas, Erio; Bolon, Brad; George, Catherine; Hardisty, Jerry F; Irizarry, Armando; McKay, Jennifer S; Odin, Marielle; Teranishi, Munehiro


    Pathology peer review verifies and improves the accuracy and quality of pathology diagnoses and interpretations. Pathology peer review is recommended when important risk assessment or business decisions are based on nonclinical studies. For pathology peer review conducted before study completion, the peer-review pathologist reviews sufficient slides and pathology data to assist the study pathologist in refining pathology diagnoses and interpretations. Materials to be reviewed are selected by the peer-review pathologist. Consultations with additional experts or a formal (documented) pathology working group may be used to resolve discrepancies. The study pathologist is solely responsible for the content of the final pathology data and report, makes changes resulting from peer-review discussions, initiates the audit trail for microscopic observations after all changes resulting from peer-review have been made, and signs the final pathologist's report. The peer-review pathologist creates a signed peer-review memo describing the peer-review process and confirming that the study pathologist's report accurately and appropriately reflects the pathology data. The study pathologist also may sign a statement of consensus. It is not necessary to archive working notes created during the peer-review process.

  3. Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN. (United States)

    Sethi, Sanjeev; Haas, Mark; Markowitz, Glen S; D'Agati, Vivette D; Rennke, Helmut G; Jennette, J Charles; Bajema, Ingeborg M; Alpers, Charles E; Chang, Anthony; Cornell, Lynn D; Cosio, Fernando G; Fogo, Agnes B; Glassock, Richard J; Hariharan, Sundaram; Kambham, Neeraja; Lager, Donna J; Leung, Nelson; Mengel, Michael; Nath, Karl A; Roberts, Ian S; Rovin, Brad H; Seshan, Surya V; Smith, Richard J H; Walker, Patrick D; Winearls, Christopher G; Appel, Gerald B; Alexander, Mariam P; Cattran, Daniel C; Casado, Carmen Avila; Cook, H Terence; De Vriese, An S; Radhakrishnan, Jai; Racusen, Lorraine C; Ronco, Pierre; Fervenza, Fernando C


    Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.

  4. Grid of depth to basement in deep-water basins offshore Washington, Oregon, and California (cowbsmg.tif) based on data collected in 1984 (United States)

    U.S. Geological Survey, Department of the Interior — COWBSMG is a 1000-m resolution grid of depth to basement off of Washington, Oregon, and California constructed from depth to basement contour data (cowbsm.shp, also...

  5. [Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology]. (United States)

    Baliasnyĭ, M M


    Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

  6. CT in vascular pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Bartolozzi, C.; Neri, E.; Caramella, D. [Diagnostic and Interventional Radiology Department of Oncology, University of Pisa, Via Roma 67, I-56100 Pisa (Italy)


    Since the introduction of helical scanners, CT angiography (CTA) has achieved an essential role in many vascular applications that were previously managed with conventional angiography. The performance of CTA is based on the accurate selection of collimation width, pitch, reconstruction spacing and scan delay, which must be modulated on the basis of the clinical issue. However, the major improvement of CT has been provided by the recent implementation of many post-processing techniques, such as multiplanar reformatting, shaded surface display, maximum intensity projections, 3D perspectives of surface and volume rendering, which simulate virtual intravascular endoscopy. The integration of the potentialities of the scanner and of the image processing techniques permitted improvement of: (a) the evaluation of aneurysms, dissection and vascular anomalies involving the thoracic aorta; (b) carotid artery stenosis; (c) aneurysms of abdominal aorta; (d) renal artery stenosis; (e) follow-up of renal artery stenting; and (f) acute or chronic pulmonary embolism. Our experience has shown that the assessment of arterial pathologies with CTA requires the integration of 3D post-processing techniques in most applications. (orig.) With 4 figs., 34 refs.

  7. Zircon U-Pb geochronology of basement metamorphic rocks in the Songliao Basin

    Institute of Scientific and Technical Information of China (English)

    PEI FuPing; XU WenLiang; YANG DeBin; ZHAO QuanGuo; LIU XiaoMing; HU ZhaoChu


    Zircon LA-ICP MS U-Pb dating of six metamorphic rocks and a metagranite (breccia) from southern basement of the Songliao Basin are reported in order to constrain the formation ages of basement. The basement metamorphic rocks in the Songliao Basin mainly consist of metagabbro (L45-1), amphibolite (SN117), metarhyolitical tuff (G190), sericite (Ser) schist (N103), chlorite (Chi) schist (T5-1), biotite (Bi)-actinolite (Act)-quartz (Q) schist (Y205), and metagranite (L44-1). The cathodoluminesence (CL)images of the zircons from metagabbro (L45-1) and metagranite (L44-1) indicate that they have cores of magmatic origin and rims of metamorphic overgrowths. Their U-Pb isotopic ages are 1808±21 Ma and 1873±13 Ma, respectively. The zircons with oscillatory zoning from amphibolite (SN117) and Chi schist (T5-1), being similar to those of mafic igneous rocks, yield ages of 274 ± 3.4 Ma and 264 ± 3.2 Ma, respectively. The zircons from metarhyolitical tuff (G190) and Ser schist (N103) display typical magmatic growth zoning and yield ages of 424 ± 4.5 Ma and 287 ± 5.1Ma, respectively. Most of zircons from Bi-Act-Q schist (Y2O5) are round in shape and different in absorption degree in the CL images, implying their sedimentary detritals. U-Pb dating yield concordant ages of 427 ± 3.1Ma, 455 ± 12 Ma, 696 ± 13 Ma,1384±62 Ma, 1649±36 Ma, 1778±18 Ma, 2450±9 Ma, 2579±10 Ma, 2793±4 Ma and 2953±14 Ma. The above-mentioned results indicate that the Precambrian crystalline basement (1808-1873 Ma) exists in the southern Songliao Basin and could be related to tectonic thrust, and that the Early Paleozoic (424-490 Ma) and Late Paleozoic magmatisms (264-292 Ma) also occur in the basin basement, which are consistent with the ages of the detrital zircons from Bi-Act-Q schist in the basement.

  8. U-Pb geochronology of basement rocks in central Tibet and paleogeographic implications (United States)

    Guynn, Jerome; Kapp, Paul; Gehrels, George E.; Ding, Lin


    The ages and paleogeographic affinities of basement rocks of Tibetan terranes are poorly known. New U-Pb zircon geochronologic data from orthogneisses of the Amdo basement better resolve Neoproterozoic and Cambro-Ordovician magmatism in central Tibet. The Amdo basement is exposed within the Bangong suture zone between the Lhasa and Qiangtang terranes and is composed of granitic orthogneisses with subordinate paragneisses and metasedimentary rocks. The intermediate-felsic orthogneisses show a bimodal distribution of Neoproterozoic (920-820 Ma) and Cambro-Ordovician (540-460 Ma) crystallization ages. These and other sparse basement ages from Tibetan terranes suggest the plateau is underlain by juvenile crust that is Neoproterozoic or younger; its young age and weaker rheology relative to cratonic blocks bounding the plateau margins likely facilitated the propagation of Indo-Asian deformation far into Asia. The Neoproterozoic ages post-date Rodinia assembly and magmatism of similar ages is documented in the Qaidaim-Kunlun terrane, South China block, the Aravalli-Delhi craton in NW India, the Eastern Ghats of India, and the Prince Charles mountains in Antarctica. The Amdo Neoproterozoic plutons cannot be unambiguously related to one of these regions, but we propose that the Yangtze block of the South China block is the most likely association, with the Amdo basement representing a terrane that possibly rifted from the active Yangtze margin in the middle Neoproterozoic. Cambro-Ordovician granitoids are ubiquitous throughout Gondwana as a product of active margin tectonics following Gondwana assembly and indicate that the Lhasa-Qiangtang terranes were involved in these tectono-magmatic events. U-Pb detrital zircon analysis of two quartzites from the Amdo basement suggest that the protoliths were Carboniferous-Permian continental margin strata widely deposited across the Lhasa and Qiangtang terranes. The detrital zircon age spectra of the upper Paleozoic Tibetan

  9. Percolation of diagenetic fluids in the Archaean basement of the Franceville basin (United States)

    Mouélé, Idalina Moubiya; Dudoignon, Patrick; Albani, Abderrazak El; Cuney, Michel; Boiron, Marie-Christine; Gauthier-Lafaye, François


    The Palaeoproterozoic Franceville basin, Gabon, is mainly known for its high-grade uranium deposits, which are the only ones known to act as natural nuclear fission reactors. Previous work in the Kiéné region investigated the nature of the fluids responsible for these natural nuclear reactors. The present work focuses on the top of the Archaean granitic basement, specifically, to identify and date the successive alteration events that affected this basement just below the unconformity separating it from the Palaeoproterozoic basin. Core from four drill holes crosscutting the basin-basement unconformity have been studied. Dating is based on U-Pb isotopic analyses performed on monazite. The origin of fluids is discussed from the study of fluid inclusion planes (FIP) in quartz from basement granitoids. From the deepest part of the drill holes to the unconformable boundary with the basin, propylitic alteration assemblages are progressively replaced by illite and locally by a phengite + Fe chlorite ± Fe oxide assemblage. Illitic alteration is particularly strong along the sediment-granitoid contact and is associated with quartz dissolution. It was followed by calcite and anhydrite precipitation as fracture fillings. U-Pb isotopic dating outlines three successive events: a 3.0-2.9-Ga primary magmatic event, a 2.6-Ga propylitic alteration and a late 1.9-Ga diagenetic event. Fluid inclusion microthermometry suggests the circulation of three types of fluids: (1) a Na-Ca-rich diagenetic brine, (2) a moderately saline (diagenetic + meteoric) fluid, and (3) a low-salinity fluid of probable meteoric origin. These fluids are similar to those previously identified within the overlying sedimentary rocks of the Franceville basin. Overall, the data collected in this study show that the Proterozoic-Archaean unconformity has operated as a major flow corridor for fluids circulation, around 1.9 Ga. highly saline diagenetic brines; hydrocarbon-rich fluids derived from organic matter

  10. Childhood Henoch-Sch(o)nlein Purpura Nephritis and IgA Nephropathy:One Disease Entity?--A Clinico-pathologically Comparative Study

    Institute of Scientific and Technical Information of China (English)


    In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schonlein purpura nephritis (HSPN), 31 children with IgA nephropathy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8 %children with IgA nephropathy, but only 10 % in HSPN (P<0.05). The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59 % had gastrointestinal symptoms and 47 % suffered from arthralgia,compared with only abdominal pain in 3.2 % children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5 % of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9 % of IgA nephropathy and 6.3 % of HSPN, but endothelial proliferation in 65.6% of HSPN and 29 % of IgA nephropathy (all P<0.01). Thin basement membrane nephropathy was only found in 6.5 % children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2 %of HSPN, and overwhelming IgG deposits in 12.5 % of HSPN with relatively weak IgA deposits,moreover 6.3 % of HSPN showed linear IgG deposits in glomerular capillary. Totally 71.9 % of HSPN had IgG deposits in glomeruli and only 19.4 % of IgA nephropathy showed glomerular IgG deposits (P<0.01). No IgG deposit was observed

  11. Garzon Massif basement tectonics: A geopyhysical study, Upper Magdalena Valley, Colombia (United States)

    Bakioglu, Kadir Baris

    The mechanics and kinematics of basement tectonic uplifts, such as the Laramide Rocky Mountain orogeny, remain poorly understood and controversial. The debate continues in part because of the limited number of well-documented present day analogs. The Garzon Massif rising between the Upper Magdalena Valley and the Llanos Basin of Colombia is an active basement uplift with well, seismic, gravity, and magnetic data available. In the past 10 Ma, PreCambrian age granitic rocks of the Garzon Massif have been uplifted and displaced against Cretaceous and Tertiary sediments of the Upper Magdalena Valley along the Garzon fault. Aerogravimetric data calibrated by well data and 2D seismic data were used to model the geometry of the Garzon fault and the top of basement (Saldana Fm) in 2 dimensions. The density models provide an independent estimate of fault orientation. A high density airborne gravity and magnetic survey were flown over the Garzon fault in 2000, including 2,663 line km along 1 x 5 and 1 x 4 km flight lines at elevations of 2564 and 4589 m above mean sea level. An initial depth model was derived from the well logs, seismic reflection profile, and down-hole velocity surveys. Airborne gravity data was used to produce a Bouguer anomaly gravity map. Average rock densities were estimated from density logs, seismic velocities, and formation rock types. The regional gravity field was estimated and 2-dimensional forward models were constructed with average densities from the wells, seismic velocities, and rock types, and the initial depth model. Since the model fit is dependent on the density assumed for the Garzon Massif rocks, multiple densities and dip angles were tested. The gravity analysis indicates that the Garzon fault is a basement thrust fault dipping at a shallow angle under the Massif. Best-fit models show a true dip of 12 to 17 degrees to the southeast. A regional density and magnetic susceptibility model of the entire Massif is consistent with dense

  12. Postcollisional mantle-derived magmatism, underplating and implications for basement of the Junggar Basin

    Institute of Scientific and Technical Information of China (English)

    韩宝福; 何国琦; 王式洸


    The late Paleozoic postcollisional granitoids, mafic-ultramafic complexes, and volcanic rocks are extensively distributed around the Junggar Basin; they are generally characterized by positive εNd(t) values, implying that the magmas were mantle-derived and contaminated with crustal materials to some extents. The emplacement of mantle-derived magmas and their differentiates in the upper crust is the expression of deep geological processes at shallow level, while much more mantle-derived magmas were underplated in the lower crust and the region near the crust-mantle boundary, being component part of basement of the Junggar Basin. The postcollisional mafic-ultramafic complexes would not be generated by re-melting of residual oceanic crust, which was considered as the basement of the Junggar Basin, unless very high degrees of partial melting occurred. Even if old continental crust had been present before collision, it would have been strongly modified by the mantle-derived magma underplating. This inter

  13. Late Riphean age of the crystalline basement of the carbonate cover of the Dzabkhan microcontinent (United States)

    Kozakov, I. K.; Kirnozova, T. I.; Kovach, V. P.; Terent'eva, L. B.; Tolmacheva, E. V.; Fugzan, M. M.; Erdenezhargal, Ch.


    The Dzabkhan microcontinent was earlier considered as a fragment of an ancient craton in the structure of the Central Asian Orogenic Belt. Deposits of the Tsagaan Oloom Formation were included in the shelf zone, under the assumption that they were related to the regional unconformity between the Early-Late Precambrian crystal formations. The carbonate sequence of the Tsagaan Oloom Formation overlaps crystalline rocks only in the eastern part of the Dzabkhan microcontinent, where dolomites lie unconformably on high-grade metamorphic rocks intruded by granitoids of the Bogdyngol massif. The latter were included in the composition of both the Early Precambrian basement and the Middle Riphean intrusive complex. We have determined the U-Pb zircon age of these granitoids at 717 ± 5 Ma and the Nd model ages of granitoids and gneisses of the basement of the Tsagaan Oloom Formation at 2.0-1.9 Ga at ɛNd = -10.0...-6.6. Recent geochronological and Nd and Pb-Pb isotopic and geochemical data indicate that intrusive and high-grade metamorphic complexes are absent in the crystalline basement of the Dzabkhan microcontinent, similar to those in ancient cratons. One can assume that the Late Riphean carbonate cover (Tsagaan Oloom Formation) deposited on the Late Precambrian continental block.

  14. Volcanic conduit migration over a basement landslide at Mount Etna (Italy). (United States)

    Nicolosi, I; Caracciolo, F D'Ajello; Branca, S; Ventura, G; Chiappini, M


    The flanks of volcanoes may slide in response to the loading of the edifice on a weak basement, magma push, and/or to tectonic stress. However, examples of stratovolcanoes emplaced on active landslides are lacking and the possible effects on the volcano dynamics unknown. Here, we use aeromagnetic data to construct a three-dimensional model of the clay-rich basement of Etna volcano (Italy). We provide evidence for a large stratovolcano growing on a pre-existing basement landslide and show that the eastern Etna flank, which slides toward the sea irrespective of volcanic activity, moves coherently with the underlying landslide. The filling of the landslide depression by lava flows through time allows the formation of a stiffness barrier, which is responsible for the long-term migration of the magma pathways from the coast to the present-day Etna summit. These unexpected results provide a new interpretation clue on the causes of the volcanic instability processes and of the mechanisms of deflection and migration of volcanic conduits.

  15. Bone pathology inpsoriatic arthritis

    Directory of Open Access Journals (Sweden)

    V. V. Badokin


    Full Text Available Objective. To study different variants of osteolysis in pts with psoriatic arthritis (PA and to reveal their relationship with other clinico-radiological features of joint damage. Material and methods. 370 pts with definite PA having different variants of joint damage were included. Radiological examination of bones and joints (in some cases large picture frame was performed. Morphological evaluation of synovial biopsies was done in 34 pts with PA and 10 pts with rheumatoid arthritis (RA. Results. Different types of osteolysis were revealed in 80 (21,6% pts. Osteolytic variant of joint damage was present in 29 pts. 33 pts had acral, 48 — intra-articular osteolysis and 16 - true bone atrophy. Frequency and intensity of bone resorption were associated with severity of PA. Acral osteolysis correlated with arthritis of distal interphalangeal joints and onychodystrophy. Intra-articular osteolysis was most often present in distal interphalangeal joints of hands and metacarpophalangeal joints (39,6% and 41,7% respectively. Characteristic feature of PA was combination of prominent resorption with formation of bone ankylosis and periosteal reaction. Ankylosis was present in 33,3% of pts with intra-articular osteolysis and in 60% of pts with combination of different osteolysis variants. Systemic reaction of microcirculation in synovial biopsies was most prominent in osteolytic variant: marked thickening of capillary and venule basal membrane with high level of acid phosphatase, increased capillary and precapillary blood flow with stasis features, vascular lymphocyte and macrophage infiltration, productive vasculitis with annular wall thickening, thrombovasculitis and villi deep layer sclerosis. Conclusion. Different variants of osteolysis show bone involvement in PA. Acral and intra- articular osteolysis association with bone ankylosis and periostitis proves their common pathogenetic entity.

  16. Cross-reactivity of cell-mediated immunity between interstitial (type I) and basement membrane (type IV) collagens



    In the present study, we demonstrate delayed-type hypersensitivity (DTH) to homologous type I collagen that cross-reacts with type IV collagen. Mice immunized with native or denatured type I collagens and challenged with these same antigens or native type IV collagen develop a peak DTH response on day 7. Challenge with denatured type IV collagen or collagenase-treated type IV collagen failed to elicit DTH in type I collagen-sensitized mice. Type I collagen-sensitized spleen cells adoptively t...

  17. The Peri-islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human

    DEFF Research Database (Denmark)

    Korpos, Eva; Kadri, Nadir; Kappelhoff, Reinhild;


    penetration of the peri-islet BM is a critical step. Protease- and protease inhibitor-specific microarray analyses (CLIP-CHIP) of laser-dissected leukocyte infiltrated and noninfiltrated pancreatic islets and confirmatory quantitative real time PCR and protein analyses identified cathepsin S, W, and C...... activity at sites of leukocyte penetration of the peri-islet BM in association with a macrophage subpopulation in NOD mice and human type 1 diabetic samples and, hence, potentially a novel therapeutic target specifically acting at the islet penetration stage. Interestingly, the peri-islet BM and underlying...

  18. AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

    DEFF Research Database (Denmark)

    Rodriguez-Teja, Mercedes; Gronau, Julian H; Breit, Claudia


    Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways...... in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major......(Δ) (Ex2-6/) (Δ) (Ex2-6) mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour...

  19. Human Papillomavirus Species-Specific Interaction with the Basement Membrane-Resident Non-Heparan Sulfate Receptor

    Directory of Open Access Journals (Sweden)

    Kathleen F. Richards


    Full Text Available Using a cell culture model where virus is bound to the extracellular matrix (ECM prior to cell surface binding, we determined that human papillomavirus type 16 (HPV16 utilizes ECM resident laminin (LN 332 as an attachment receptor for infectious entry. In presence of LN332, soluble heparin can function as ligand activator rather than competitive inhibitor of HPV16 infection. We also show that the ability to use LN332 binding as a productive attachment step for infectious entry is not conserved amongst HPV types. In the alpha genus, species 9 members (HPV16 attach to ECM via LN332, while members of species 7 (HPV18 are completely inhibited by heparin pre-incubation due to an inability to use LN332. Since HPV species 7 and 9 are preferentially associated with adenocarcinoma and squamous cell carcinoma of the cervix, respectively, our data provide first evidence that pre-entry events may contribute to the anatomical-site preference of HPV species.

  20. Geochemical variability of the Yucatan basement: Constraints from crystalline clasts in Chicxulub impactites (United States)

    Kettrup, B.; Deutsch, A.


    The 65 Ma old Chicxulub impact structure with a diameter of about 180 km is again in the focus of the geosciences because of the recently commenced drilling of the scientific well Yaxcopoil- 1. Chicxulub is buried beneath thick post-impact sediments, yet samples of basement lithologies in the drill cores provide a unique insight into age and composition of the crust beneath Yucatan. This study presents major element, Sr, and Nd isotope data for Chicxulub impact melt lithologies and clasts of basement lithologies in impact breccias from the PEMEX drill cores C-1 and Y-6, as well as data for ejecta material from the K/T boundaries at La Lajilla, Mexico, and Furlo, Italy. The impact melt lithologies have an andesitic composition with significantly varying contents of Al, Ca, and alkali elements. Their present day 87Sr/86Sr ratios cluster at about 0.7085, and 143Nd/144Nd ratios range from 0.5123 to 0.5125. Compared to the melt lithologies that stayed inside the crater, data for ejecta material show larger variations. The 87Sr/86Sr ratios range from 0.7081 for chloritized spherules from La Lajilla to 0.7151 for sanidine spherules from Furlo. The 143Nd/144Nd ratio is 0.5126 for La Lajilla and 0.5120 for the Furlo spherules. In an tCHUR(Nd)-tUR(Sr) diagram, the melt lithologies plot in a field delimited by Cretaceous platform sediments, various felsic lithic clasts and a newly found mafic fragment from a suevite. Granite, gneiss, and amphibolite have been identified among the fragments from crystalline basement gneiss. Their 87Sr/86Sr ratios range from 0.7084 to 0.7141, and their 143Nd/144Nd ratios range from 0.5121 to 0.5126. The TNdDM model ages vary from 0.7 to 1.4 Ga, pointing to different source terranes for these rocks. This leads us to believe that the geological evolution and the lithological composition of the Yucatàn basement is probably more complex than generally assumed, and Gondwanan as well as Laurentian crust may be present in the Yucatàn basement.

  1. Utilization management in anatomic pathology. (United States)

    Lewandrowski, Kent; Black-Schaffer, Steven


    There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management.

  2. Organic chemistry of fluids from sediment-buried young basement: discrete sampling from ODP borehole 1301A & 1025C (United States)

    Lin, H.; Cowen, J. P.; Amend, J. P.; Albert, D. B.; Glazer, B. T.; Rappe, M.; Jungbluth, S.; Matzinger, M.


    Hydrothermal systems profoundly influence seawater chemistry. However, the extent to which hydrothermal systems impact the quantity and the quality of the deep ocean dissolved organic carbon (DOC) pool remains unclear. To study the organic chemistry within sedimented ridge flank basement aquifers, discrete low temperature (~65°C & ~40°C) basement fluids were collected from Integrated Ocean Drilling Program boreholes via Circulation Obviation Retrofit Kit (CORK) observatories at 1301A (47°45N, 127°45W) and 1025C (47°53N, 128°39W) on the eastern flank of Juan de Fuca Ridge. The basement age is 1.24 Ma and 3.5 Ma at 1025C and 1301A, respectively. Basement fluids were collected using a new clean pumping system (Mobile Pump Valve Unit, or MPVU) and stored in acid-cleaned 60 L Large Volume Tedlar Bags (LVBS). A stainless steel fluid delivery line extends from the basement to the seafloor at 1301A; whereas fluids rise up the middle of the iron casing at 1025C. Here, concentration and preliminary characterization of the DOC will be presented, including labile organic components such as dissolved free and combined amino acids (DFAA & DCAA) and low molecular weight organic acids (LMW-OA). Our data show that compared to seawater levels, the DOC concentration in the younger basement fluid (1025C) was about one-half and in the older (1031A) was less than one-third. Relative to bottom seawater, the basement fluids are also depleted in SO42-, PO43-, NO3- and NO2-, but enriched in NH4+, H2S, Mn and Fe. Microbially mediated reduction of nitrate, sulfate, iron, and manganese and an array of heterotrophic metabolisms may explain these observations. Phylogenic trees based on 16S rRNA gene sequences from borehole 1301A fluids further support the presence of chemolithoautotrophic and heterotrophic organisms. Our preliminary results show that some dissolved free amino acids were slightly enriched in the 1301A basement fluid relative to bottom seawater. Thermodynamic calculations

  3. Using the IODP Expedition 312 Vertical Seismic Profile to Investigate Sub-basement Reflections in Multi-Channel Profiles (United States)

    Nag, S.; Swift, S. A.; Stephen, R. A.


    The Ocean Drilling Program (ODP) initiated drilling at Site 1256D in the Guatemala Basin, about 1000km off the East Pacific Rise to penetrate plutonic rocks, anticipated to be relatively shallow in this region formed at an ultra- fast spreading rate. IODP Expedition E312 successfully drilled into gabbros at ~ 1150m in basement. Multi- channel seismic traces, although not processed for the purpose, show weak laterally-coherent sub-basement reflections at borehole depths (Hallenborg et. al., Journal of Geophysical Research, Vol 108 No. B11, 2532, 2003). Synthetic reflectivity seismograms were computed using a Ricker wavelet and impedance profiles from borehole sonic logs. They strongly suggest the presence of significant sub-basement amplitude peaks - although attenuation has not been modeled. Zero-offset vertical seismic profiles were processed to investigate the authenticity of these reflections and interpret the geological features that caused them. A dual scheme of the median filtering and F-K dip filtering was used. Down-going energy is clearly identified but negligible up-going energy is visible over random noise. The absence of geophones above the basement prevents comparison of basement reflections with sub-basement ones, so that a critical energy level above the noise could be established to identify up-going energy. The negative results are consistent with the topography of geological horizons on horizontal scales less than the Fresnel Zone (~ 300m). This expedition is the first penetration through volcanic extrusives and dikes into plutonic basement. In such a setting, sub-basement reflections, if present, would have been accurately measured. Absence of such clear and comprehensible observations in this area strongly suggests that lava flows and igneous contacts in upper ocean crust have significant topography on lateral scales < 300 m due to igneous and tectonic processes.

  4. Effects of Yishentongluo decoction on the expression of PAI-1, biochemical and pathological indicators in rat with experimental membranous nephropathy%益肾通络方对膜性肾病SD大鼠肾组织纤溶酶原激活物抑制因子-1及生化、病理指标的影响

    Institute of Scientific and Technical Information of China (English)

    王刚; 袁国栋; 檀金川


    织中的表达,减轻足变融合,促进受损的肾小球基底膜修复,从而减轻肾脏损伤,延缓肾脏慢性病理进展.%Objective To observe the Effects of Yishentongluo Decoction on the expression of PAI - 1 on experimental membranous nephropathy. Methods 40 SD rats were randomly divided into four groups; control group, model group, western medicine group and Chinese herb group ( n = 10, in each group). Model group, western medicine group and Chinese herb group received tail vein injection of 2. 5 mg of cationic bovine serum albumin ( C - BSA) (dissolved in 1 Ml Ph value of 7.4 phosphate buffer) , 3 times a week for 4 weeks. After the modeling, the normal group and model group were fed by saline. Western medicine group received benazepril tablets dissolved in 5ml normal saline at 10 mg/kg daily. Chinese herb group received Yishentongluo decoction 5 Ml, once a day for 4 weeks. Mouse serum albumin (Alb), total protein (TP), triglycerides (TG) and total cholesterol (TC) were detec-ted using automatic biochemical analyzer; the determination ' of 24 h urinary protein was completed by biuret method for; immunoglobulin G ( IgG) and complement 3 ( C3 ) were measured by indirectimmunofluorescence detection, the glo-merular basement membrane and foot process changes were observed using transmission electron microscopy, PAI - 1immunohistochemistry was completed by the use of streptococcus avidin - biotin - peroxidase complex ( SABC) method. Results TP and Alb of the blood serum in model group, western medicine group and Chinese herb group were significantly decreased as compared with those in control group ( P 0.05). IgG and C3 in model group, western medicine and Chinese herb group showed granular climbing along the capillary and part of deposition. Deposition in western medicine group and Chinese herb group was significantly decreased as compared with that in model group (P 0. 05 ). Conclusion Yishentongluo decoction can reduce proteinuria, increase plasma

  5. MLE's bias pathology motivates MCMLE


    Yatracos, Yannis G.


    Maximum likelihood estimates are often biased. It is shown that this pathology is inherent to the traditional ML estimation method for two or more parameters, thus motivating from a different angle the use of MCMLE.

  6. [Methods and methodology of pathology]. (United States)

    Lushnikov, E F


    The lecture gives the state-of-the-art of the methodology of human pathology that is an area of the scientific and practice activity of specialists to produce and systematize objective knowledge of pathology and to use the knowledge in clinical medicine. It considers the objects and subjects of an investigation, materials and methods of a pathologist, and the results of his/her work.

  7. Systemic disorders affecting dental pathology

    Directory of Open Access Journals (Sweden)

    Knežević Milan R


    Full Text Available A retrospective overview of systemic disorders which might be associated with dental pathology is made. They are grouped as follows: (a congenital dental developmental disorders, (b chromosomal anomalies, (c radiations, (d immune disorders, (e intoxications, (f neurological alterations, (g gastrointestinal diseases, (h osteodystrophy and associated conditions, (i skin diseases, (j metabolic and endocrine disorders, (k craniofacial malformation syndromes and other congenital general malformations. The associated dental pathology is described in each case.

  8. Development of pathology in Turkey

    Directory of Open Access Journals (Sweden)

    Gökhan GEDİKOĞLU


    Full Text Available Autospy is an important tool for the development of pathology as a science. In western civilisation dissection of human body became widespread with Renaissance, in contrast in the Ottoman Empire first dissection was not performed until the 19th century. Mustafa Behçet Efendi, head physician of the Empire, was one of the Ottoman physician who suggested the importance of dissection in the medical education. The first dissection was however performed by Charles Ambroise Bernard, a foreign physician who had been invited to help establishing a new medical school; “Mekteb-i Tıbbiye-i Adliye-i Şâhâne”, in 1843. The first modern medical schools called “Tıphane” and “Cerrahhane-i Amire” which were founded in 1827, did not have pathology courses. Pathology courses began in “Mekteb-i Tıbbiye-i Adliyei Şâhâne”. Dr. Hamdi Suat (Aknar, educated in anatomic pathology in Germany, was the first pathologist who established the modern pathology in Turkey in “İstanbul Darülfünun” medical school. In 1933 “Darülfünün” was closed and İstanbul University was built and the “University Reform Commission” invited many scientists escaping from Nazi government to study in İstanbul University. Dr. Philipp Schwartz had an important role both in the invitation of these scientists and establishment of the pathology department in İstanbul University. Practical courses were increased, clinicopathologic courses were organized for the first time and a lot of autopsies were performed, as high as 1000 autopsy per year, by Dr. Philipp Schwartz. More progress has takes place in Turkey over the years since pathology was first established. Today Turkey has many pathology departments which keep up with the worldwide advances in the field.

  9. 膀胱白斑四型法病理分型及临床意义%Pathological classification of vesical leukoplakia

    Institute of Scientific and Technical Information of China (English)

    唐秀英; 叶章群; 官阳; 邢金春; 李良玉; 唐敏


    目的 探讨膀胱自斑的病理分型及其临床意义.方法 经膀胱镜下活检病理确诊膀胱白斑患者726例.女710例,男16例.平均年龄41(17~78)岁.随机取白斑边缘旁1.0、1.5、2.0、2.5 cm处膀胱黏膜共121例次,同期50例慢性膀胱炎膀胱黏膜标本作为对照,根据膀胱白斑的病理特点进行病理分型.并与传统分型法比较.结果 726例标本根据细胞变异程度、鳞状细胞角化程度、基膜形状等不同分为4型:0型30例、Ⅰ型42例、Ⅱ型585例、Ⅲ型69例.而按传统分型法其中60例难以确切分型.101例白斑边缘旁2.0 cm内膀胱黏膜标本中已存在病理改变64例.结论 膀胱白斑4型病理分型法可较全面地反映膀胱自斑的病理特点及发生、发展过程.根据病理分型可考虑改进膀胱白斑的传统治疗方式.%Objective To discuss the pathological classification and clinical features of vesical leukoplakia.Methods Seven hundred and twenty-six consecutive cases diagnosed of vesical leukoplakia with cystoseopy and biopsy were reviewed.The mean age was 41 years(range 17 to 78),710 females and 16 males.Of these 726 cases,121 biopsies were undergone randomly at the sites of 1.0 cm,1.5 cm,2.0 cm and 2.5 cm away from vesical leukoplakia margins.The pathologic characteristics of vesical leukoplakia were observed and compared simultaneously with the results of 50 specimens of chronic cystitis.The new pathological classification system was carried out and compared with the traditional one.Results According to the difference in the degree of the cell variation,the degree of keratinizing squamous metaplasia and the shape of basement membrane,the lesions were divided into 4 types.Of these 726 cases,30 type 0(4.1%),42 type Ⅰ(5.8%),585 type Ⅱ(80.6 0A),and 69 type Ⅲ(9.5%).Sixty samples were difficult to be classified by traditional classification system.There were 101 biopsies within 2.0 cm para-leukoplakia area,and 64 of them had presented with

  10. Basement-driven strike-slip deformation involving a salt-stock canopy system (United States)

    Dooley, Tim; Jackson, Martin; Hudec, Mike


    NW-striking basement-involved strike-slip zones have been reported or inferred from the northern Gulf of Mexico (GoM). This interpretation is uncertain, because the effects of strike-slip deformation are commonly difficult to recognize in cross sections. Recognition is doubly difficult if the strike-slip zone passes through a diapir field that complicates deformation, and an associated salt canopy that partially decouples shallow deformation from deep deformation. We use physical models to explore the effects of strike-slip deformation above and below a salt-stock canopy system. Canopies of varying maturity grew from a series of 14 feeders/diapirs located on and off the axis of a dextral basement fault. Strike-slip deformation styles in the overburden vary significantly depending on: (1) the location of the diapirs with respect to the basement fault trace, and; (2) the continuity of the canopy system. On-axis diapirs (where the diapirs lie directly above the basement fault) are typically strongly deformed and pinched shut at depth to form sharp S-shapes, whereas their shallow deformation style is that of a open-S-shaped pop-up structure in a restraining bend. The narrow diapir stem acts as a shear zone at depth. Pull-apart structures form between diapirs that are arranged in a right-stepping array tangental to the basement fault trace. These grade along strike into narrow negative flower structures. Off-axis diapirs (diapirs laterally offset from the basement fault but close enough to participate in the deformation) form zones of distributed deformation in the form of arrays of oblique faults (R shears) that converge along strike onto the narrower deformation zones associated with on-axis diapirs. Above an immature, or patchy, canopy system the strike-slip structures closely match sub canopy structures, with the exception of wrench fold formation where the supracanopy roof is thin. In contrast, the surface structures above a mature canopy system consist of a broad

  11. Mapping of Basement Faults with Gravity and Magnetic Data at NE Mexico (United States)

    Yutsis, V.; Krivosheya, K.; Tamez Ponce, A.


    Northeast Mexico is essentially the juncture of two distinctly different tectono-stratigraphic provinces, the eastern Gulf of Mexico (Coastal Plane, Sierra Madre Oriental) province and the western Pacific Mexico (Rivera plate, Meso-American trench, Sierra Madre Occidental) province (Goldhammer & Johnson, 2001). Tectonic evolution in northeast Mexico is dominated by divergent-margin development associated with the opening of the Gulf of Mexico and overprinted by non-igneous Laramide orogenic effects (Pindell et al., 1988). The structural grain of northeast Mexico consists of Triassic to Liassic fault-controlled basement blocks, the development of which reflects in part late Paleozoic orogenic patterns of metamorphism and igneous intrusion (Wilson, 1990). There are different tectonic provinces which are recognized interpreting the basement and sediment cover of this area: Coahuila block, La Popa sub-basin, Sabinas basin, Burgos basin, Sierra Madre Oriental (Monterrey trough), and Parras basin. Mojave-Sonora megashear and San Marcos fault (Chavez-Cabello et al., 2007) are two principal fault zones crossing the northeast Mexico in NW-SE direction. This paper is presented the integral analysis of the gravity and magnetic data in the northeast Mexico. Complementing with a Digital Model of Elevations (DME) that combined with the review of previous geological studies it serves to compare the surface structures and blocks of basement in this area. Also the separation of the most important tectonic blocks was done, and 2.5D geological-geophysical model was finally developed. This model represents in a general way the principal structural characteristics of northeast Mexico. Gravity and magnetic data analysis was used with purpose to study the structure of the substrata in order to allow modeling of the basement structure and its relation with the sedimentary cover features. The Bouguer gravity and the total field aeromagnetic data were supplied by Geological Survey of Mexico

  12. Loss of Bin1 Promotes the Propagation of Tau Pathology

    Directory of Open Access Journals (Sweden)

    Sara Calafate


    Full Text Available Tau pathology propagates within synaptically connected neuronal circuits, but the underlying mechanisms are unclear. BIN1-amphiphysin2 is the second most prevalent genetic risk factor for late-onset Alzheimer’s disease. In diseased brains, the BIN1-amphiphysin2 neuronal isoform is downregulated. Here, we show that lowering BIN1-amphiphysin2 levels in neurons promotes Tau pathology propagation whereas overexpression of neuronal BIN1-amphiphysin2 inhibits the process in two in vitro models. Increased Tau propagation is caused by increased endocytosis, given our finding that BIN1-amphiphysin2 negatively regulates endocytic flux. Furthermore, blocking endocytosis by inhibiting dynamin also reduces Tau pathology propagation. Using a galectin-3-binding assay, we show that internalized Tau aggregates damage the endosomal membrane, allowing internalized aggregates to leak into the cytoplasm to propagate pathology. Our work indicates that lower BIN1 levels promote the propagation of Tau pathology by efficiently increasing aggregate internalization by endocytosis and endosomal trafficking.

  13. Thermochronology and geochemistry of the Pan-African basement below the Sab'atayn Basin, Yemen (United States)

    Veeningen, Resi; Rice, A. Hugh N.; Schneider, David A.; Grasemann, Bernhard


    Three important lithologies occur in two drill wells from the Pan-African basement underlying the Mesozoic Sab'atayn Basin, in a previously undocumented area of the Pan-African, 83 and 90 km NE of known exposures in Yemen. Cores from well 1 include amphibolite, with basaltic to andesitic compositions, affected by crustal contamination during emplacement into a thickened crust. Deeper in the well, an unfoliated dark red monzogranite has a U-Pb zircon age of 628.8 ± 3.1 Ma and a Rb-Sr biotite cooling age of 591.6 ± 5.8 Ma (∼300 °C). Regional constraints suggest emplacement in a transitional tectonic setting with compressional terrane amalgamation followed by extensional collapse. Sm-Nd isotope analysis yields a TDM model age of 1.24 Ga with negative εNd values, suggesting the monzogranite is part of the Al Bayda island arc terrane. Cores from well 2 contains a weakly deformed, massive (unbedded) medium grey meta-arkose exhibiting essentially no geochemical signature of weathering and with an almost pure dacitic composition. This rock may have been directly derived from an (extrusive) granitoid that was emplaced prior to, or during terrane amalgamation. A (U-Th-Sm)/He zircon age of 156 ± 14 Ma constrains the time of basement cooling to ∼180 °C, synchronous with basin formation. These lithologies provide new insights in the development of the Pan-African basement of Yemen, extending our knowledge of the nearby surface geology to the subsurface.

  14. The role of mechanical heterogeneities in evaporite sequence during deformation initiated by basement fault activity (United States)

    Adamuszek, Marta; Dabrowski, Marcin; Burliga, Stanisław


    Kłodawa Salt Structure (KSS) situated in the centre of the Polish Zechstein Basin started to rise above a basement fault in the Early Triassic. Geological studies of the KSS revealed significant differences in the deformation patterns between the PZ1-PZ2 (intensely deformed) and PZ3-PZ4 (less deformed) cycle evaporites. These two older and two younger cycle evaporite complexes are separated by the thick Main Anhydrite (A3) bed. We use numerical simulations to assess the impact of a thick anhydrite bed on intrasalt deformation. In our models, the overburden consists of clastic sediments. A normal fault located in the rigid basement beneath the salt is activated due to model extension. At the same time, the sedimentation process takes place. The evaporites consist of a salt bed intercalated with a thick anhydrite layer of varying position and geometry. To understand the role of anhydrite layer, we run comparative simulations, in which no anhydrite layer is present. In the study, we use our own numerical codes implemented in MATLAB combined with the MILAMIN and MUTILS numerical packages. Our investigations revealed a significant influence of the anhydrite on deformation style in the evaporate series. The supra-anhydrite domain is characterized by weaker deformation and lower rates of salt flow in comparison to the sub-anhydrite domain. The highest contrast in the rate of salt flow between the two domains is observed in the case of the anhydrite layer situated close to the bottom of the salt complex. The thick anhydrite layer additionally diminishes the deformation rate in the supra-anhydrite domain and can lead to detachment of the basement deformation from its overlay. Our numerical simulations showed that the presence of the A3 Main Anhydrite bed could be the dominant factor responsible for the decoupling of deformation in the KSS salt complex.

  15. Structure of Charnockitic basement in a part of the Krishna–Godavari basin, Andhra Pradesh

    Indian Academy of Sciences (India)

    I V Radhakrishna Murthy; S Bangaru Babu


    A regional magnetic survey was carried out over an area of 8000 km2 in Godavari districts of Andhra Pradesh,India,which is covered by the rocks of Eastern Ghat Mobile Belt (EGMB) viz., the Khondalitic series and Charnockites in the northern half and Permian to Mesozoic and Cenozoic sediments in the southern half,and forms a part of the Krishna –Godavari (K –G)basin. The survey brought out a strong NE –SW trending anomaly in the area covered by the rocks of Eastern Ghat Mobile Belt (EGMB),and a mild ENE –WSW trending anomaly in the area covered by the sediments of the Krishna –Godavari (K –G)basin.The NE –SW trending anomaly in the northern half could be attributed to the exposed/near surface Charnockite basement that has come closer to the surface as a result of Eastern Ghat Mobile Belt (EGMB)tectonics.Explanation of the mild ENE –WSW trending anomaly over the sediments of the Krishna –Godavari (K –G)basin required a faulted magnetic basement at depth downthrown towards the south.It is therefore concluded that the Charnockitic basement together with the Khondalite group of rocks which are folded and faulted during the different phases of tectonics of Eastern Ghat Mobile Belt (EGMB) extend into the Krishna –Godavari (K –G)basin and further,were involved in faulting during the phases of formation and sedimentation in the Krishna –Godavari (K –G)basin.

  16. IODP Expeditions 309 and 312 Drill an Intact Section of Upper Oceanic Basement into Gabbros

    Directory of Open Access Journals (Sweden)

    Douglas S. Wilson


    Full Text Available The Integrated Ocean Drilling Program’s (IODP Expeditions 309 and 312 successfully completed the first sampling of an intact section of upper oceanic crust, through lavas and the sheeted dikes into the uppermost gabbros. Hole 1256D, which was initiated on the Ocean Drilling Program’s (ODP Leg 206, now penetrates to >1500 mbsf and >1250 m sub-basement. The first gabbroic rocks were encountered at 1407 mbsf. Below this, the hole penetrates ~100 m into a complex zone of fractionated gabbros intruded into contact metamorphosed dikes.


    Directory of Open Access Journals (Sweden)

    Parul Dutta


    Full Text Available The hip joint is a large and complex articulation and can be involved by numerous pathologic conditions like congenital and developmental, infective, arthritic, and neoplastic. Early diagnosis and characterisation of pathology has vital role in proper management and follow up of the disease for the clinicians. Present study was conducted in 45 patients who underwent clinical, radiological, and pathological examination in GMCH. Maximum no of patient between age group of 10-30 yrs. male-female ratio was 1.8:1 and 30% cases are unilateral. FSE STAIR images were most useful in delineating pathologies. Gadolinium-enhanced scan were used to evaluate the extent of the disease and the pattern of involvement. AVN was the most common pathology detected comprising 29%. The next common abnormality detected was infective arthritis found in 26% of cases. In case of Legg-Calve-Perthes disease, there was abnormal linear increase in the signal intensity at junction of the epiphyseal cartilage. Ultrasonography is useful for the screening of paediatric hip cases and also for guided aspiration for histopathology. CT scan shows better resolution of soft tissue then the radiograph. The importance of early diagnosis can be gauzed from the fact that early initiation of treatment creates the difference between a responsible, worthwhile life, and a cripple handicapped life. The role of imaging can never be undermined considering the fact that early suspicion and detection is within the realms of imaging.

  18. Communication skills in diagnostic pathology. (United States)

    Lehr, Hans-Anton; Bosman, Fred T


    Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

  19. Alternative Pathway Dysregulation and the Conundrum of Complement Activation by IgG4 Immune Complexes in Membranous Nephropathy (United States)

    Borza, Dorin-Bogdan


    Membranous nephropathy (MN), a major cause of nephrotic syndrome, is a non-inflammatory immune kidney disease mediated by IgG antibodies that form glomerular subepithelial immune complexes. In primary MN, autoantibodies target proteins expressed on the podocyte surface, often phospholipase A2 receptor (PLA2R1). Pathology is driven by complement activation, leading to podocyte injury and proteinuria. This article overviews the mechanisms of complement activation and regulation in MN, addressing the paradox that anti-PLA2R1 and other antibodies causing primary MN are predominantly (but not exclusively) IgG4, an IgG subclass that does not fix complement. Besides immune complexes, alterations of the glomerular basement membrane (GBM) in MN may lead to impaired regulation of the alternative pathway (AP). The AP amplifies complement activation on surfaces insufficiently protected by complement regulatory proteins. Whereas podocytes are protected by cell-bound regulators, the GBM must recruit plasma factor H, which inhibits the AP on host surfaces carrying certain polyanions, such as heparan sulfate (HS) chains. Because HS chains present in the normal GBM are lost in MN, we posit that the local complement regulation by factor H may be impaired as a result. Thus, the loss of GBM HS in MN creates a micro-environment that promotes local amplification of complement activation, which in turn may be initiated via the classical or lectin pathways by subsets of IgG in immune complexes. A detailed understanding of the mechanisms of complement activation and dysregulation in MN is important for designing more effective therapies. PMID:27199983

  20. Ultrastructural Pathologic Observation on the Gut-Associated Lymphoid Tissues of Sacculus Rotundus of Rabbits Infected with Rabbit Haemorrhagic Disease Virus

    Institute of Scientific and Technical Information of China (English)

    SHE Rui-ping; YANG Han-chun; JIA Jun-zheng; LIU Hai-hong; MA Yi-xin; Itakura C


    Ultrastructural pathological changes in the gut-associated lymphoid tissues of sacculus rotundus(SR) of rabbits infected with rabbit haemorrhagic disease virus (RHDV) were first observed. There were nu-merous holes at the luminal and basement membrane surfaces of the dome epithelium(DE), consistently ac-companied by necrosis of lymphocytes and M-cells, and pronounced depletion of lymphocytes in the domes andfollicles, decrease of DE complex with formation of pseudomembranous structure on the surface of the domeepithelium. A specific finding in lymphocytes and macrophages was that severe destruction detraction of themembrane of rough endoplasmic reticulum(RER) was accompanied by conspicious increase of solitary, ribo-some-like particles in the cytoplasm, with appearances of intranuclear particles and intranuclear inclusions. Itwas found that there were many round and dense virion-like particles, with 26 nm in diameter, in the nucleiand cytoplasm of lymphoctes, plasma cells, macrophages and fibroblasts, or in degenerated cells and cellulardebris. At the same time, another round virion-like particles about 34 nm in diameter were also seen in the cy-toplasm of some cells and interstitium. The results indicated that the appearances of the ribosome-like parti-cles, virion-like particles and inclusion bodies were related to the replication and assembly of RHDV. Thepresent observations suggested that DE of sacculus rotundus could be a open pathway and a transporting routefor the entry of antigens into hosts. While the antigen is profoundly deleterious, DE may be as a closed portalor a barrier preventing the foreign antigenic materials from invading.

  1. Poloxamer-188 and citicoline provide neuronal membrane integrity and protect membrane stability in cortical spreading depression. (United States)

    Yıldırım, Timur; Eylen, Alpaslan; Lule, Sevda; Erdener, Sefik Evren; Vural, Atay; Karatas, Hulya; Ozveren, Mehmet Faik; Dalkara, Turgay; Gursoy-Ozdemir, Yasemin


    Under pathological conditions such as brain trauma, subarachnoid hemorrhage and stroke, cortical spreading depression (CSD) or peri-infarct depolarizations contribute to brain damage in animal models of neurological disorders as well as in human neurological diseases. CSD causes transient megachannel opening on the neuronal membrane, which may compromise neuronal survival under pathological conditions. Poloxamer-188 (P-188) and citicoline are neuroprotectants with membrane sealing properties. The aim of this study is to investigate the effect of P-188 and citicoline on the neuronal megachannel opening induced by CSD in the mouse brain. We have monitored megachannel opening with propidium iodide, a membrane impermeable fluorescent dye and, demonstrate that P-188 and citicoline strikingly decreased CSD-induced neuronal PI influx in cortex and hippocampal dentate gyrus. Therefore, these agents may be providing neuroprotection by blocking megachannel opening, which may be related to their membrane sealing action and warrant further investigation for treatment of traumatic brain injury and ischemic stroke.


    Directory of Open Access Journals (Sweden)



    Full Text Available INTRODUCTION: Amniotic membrane is the innermost layer of the f etal membranes. It has a stromal matrix, a collagen layer, and an overlying basement membrane with a single layer of epithelium. (1 Amniotic membrane has unique properties including an ti-adhesive effects, bacterio-static properties, wound protection, pain redu ction, and epithelialisation effects. Another characteristic of amniotic membrane is the lack of imunogenicity. (2 Amniotic membranes have been used as a dressing to promote he aling of chronic ulcers of the leg and as a biological dressing for burned skin and skin woun ds. (3, 4 It has also been used in surgical reconstruction of artificial vagina, for repairing o mphaloceles, and to prevent tissue adhesion in surgeries of the abdomen, head, or pelvis. (5, 6 Amniotic membrane has been successfully used in ocular conditions like persistent epithelial defects (7, pterygium, (8 Symblepharon (9 and for ocular surface reconstruction. (10, 11 The purpose of this study was to evaluate the use of cryo- preserved Human amniotic membrane graft( HAMT, with or without limbal autograft transplantation (LAT in patients with previous and fr esh chemical eye injuries respectively. Institutional ethical committee approval was obtained .

  3. Cytocompatibility of Three Corneal Cell Types with Amniotic Membrane

    Institute of Scientific and Technical Information of China (English)

    CHENJian-su; CHENRui; XUJin-tang; DINGYong; ZHAOSong-bin; LISui-lian


    Rabbit limbal corneal epithelial cells, corneal endothelial cells and keratocytes were cultured on amniotic membrane. Phase contrast microscope examination was performed daily. Histological and scan electron microscopic examinations were carried out to observe the growth, arrangement and adhesion of cultivated cells. Results showed that three corneal cell types seeded on amniotic membrane grew well and had normal cell morphology. Cultured cells attached firmly on the surface of amniotic membrane. Corneal epithelial cells showed singular layer or stratification. Cell boundaries were formed and tightly opposed. Corneal endothelial cells showed cobblestone or polygonal morphologic characteristics that appeared uniform in size. The cellular arrangement was compact. Keratocytes elongated and showed triangle or dendritic morphology with many intercellular joints which could form networks. In conclusion, amniotic membrane has good scaffold property, diffusion effect and compatibility with corneal cells. The basement membrane side of amniotic membrane facilitated the growth of corneal epithelial cells and endothelial cells and cell junctions were tightly developed. The spongy layer of amniotic membrane facilitated the growth of keratocytes and intercellular joints were rich. Amniotic membrane is an ideal biomaterial for layering tissue engineered cornea.

  4. Robotic membranes

    DEFF Research Database (Denmark)

    Ramsgaard Thomsen, Mette


    , Vivisection and Strange Metabolisms, were developed at the Centre for Information Technology and Architecture (CITA) at the Royal Danish Academy of Fine Arts in Copenhagen as a means of engaging intangible digital data with tactile physical material. As robotic membranes, they are a dual examination...

  5. Treatment strategies in mucous membrane pemphigoid

    Directory of Open Access Journals (Sweden)

    Ann G Neff


    Full Text Available Ann G Neff, Matthew Turner, Diya F MutasimDepartment of Dermatology, University of Cincinnati, Cincinnati, OH, USAAbstract: Mucous membrane pemphigoid (MMP is an autoimmune blistering disorder that is characterized by subepithelial bullae. Various basement membrane zone components have been identified as targets of autoantibodies in MMP. Considerable variability exists in the clinical presentation of MMP. Mucous membranes that may be involved include the oral cavity, conjunctiva, nasopharynx, larynx, esophagus, genitourinary tract, and anus. A multidisciplinary approach is essential in the management of MMP. Early recognition of this disorder and treatment may decrease disease-related complications. The choice of agents for treatment of MMP is based upon the sites of involvement, clinical severity, and disease progression. For more severe disease, or with rapid progression, systemic corticosteroids are the agents of choice for initial treatment, combined with steroid-sparing agents for long-term maintenance. Due to the rarity of this disease, large controlled studies comparing the efficacy of various agents are lacking.Keywords: mucous membrane pemphigoid, cicatricial pemphigoid

  6. Pharmacological Treatments in Pathological Gambling

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N


    AIMS: Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behavior. Although common and financially devastating to individuals and families, there currently exist no formally approved...... pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. METHODS: A systematic review of the 18 double-blind, placebo-controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean...

  7. Optimal breast cancer pathology manifesto. (United States)

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A


    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way.

  8. 溶酶体相关膜蛋白2基因新突变导致Danon病的临床病理特点%Clinical and pathological features of Danon disease associated with a novel lysosome-associated membrane protein-2B mutation

    Institute of Scientific and Technical Information of China (English)

    洪道俊; 石志鸿; 张巍; 王朝霞; 袁云


    目的 报道1例Danon病患者的临床表现、病理改变特点和基因突变位点.方法 16岁男性患者表现为缓慢进展的骨骼肌无力和萎缩,以近端为主,伴随轻度脊柱强直.心电图示Ⅰ度房室传导阻滞,心脏超声示二尖瓣局限性增厚伴舒张功能损害,肌电图提示神经源性合并肌源性损害.患者左腓肠肌活体组织检查后,进行组织学、酶组织化学、电镜观察及抗肌营养不良素蛋白、层黏连蛋白α2、C5b9等免疫组织化学染色.患者及其父母进行溶酶体相关膜蛋白2(LAMP2)B基因的直接测序.结果 骨骼肌纤维内出现大小不一的自嗜空泡和镶边空泡,空泡内缺乏糖原,免疫组织化学显示多数肌纤维内的空泡边缘出现肌营养不良素蛋白、层黏连蛋白α2和C5b9的表达.电镜显示肌纤维内大量膜性空泡和溶酶体聚集.患者的LAMP2B基因9号外显子存在K402X突变,患者母亲无此突变,50名健康对照无此突变.结论 LAMP2B的9号外显子羧基末端的截断突变可以导致相对良性的Danon病,其心脏损害相对轻微.%Objectives To report the clinical and myopathological features in a case with Danon disease caused by a novel mutation in the lysosome-associated membrane protein-2 ( LAMP2 ) B gene.Methods A 16-year-old boy presenting progressive muscle weakness and atrophy, accompanied with spinal ankylosis was clinically evaluated including electrocardiogram, echocardiogram and electromyogram.Muscle biopsy was carried out in the patient.The histological staining, ultrastructural examination, and immunohistochemical staining with antibodies against dystrophin, merosin and C5b9 were performed in frozen sections.LAMP2B sequence was analyzed in the patient and his parents.Results Electrocardiogram in the patient showed Ⅰ atrioventricular block; echocardiogram revealed focal hypertrophy in mitral valve with mild cardiac diastolic dysfunction; electromyogram indicated myogenic and neurogenic

  9. Fractured-basement reservoir modeling using continuous fracture modeling (CFM) method (United States)

    Isniarny, Nadya; Haris, Abdul; Nurdin, Safrizal


    The challenge in oil and gas exploration has now shifted due to increasingly difficult to get back up economic value in a conventional reservoir. Explorationist are developing various drilling technology, optimizing conventional reserves and unconventional reserve in reservoirs. One of the unconventional reservoir that has been developed is the basement reservoir. This rock type has no primary porosity and the permeability of the rocks of this type are generally influenced by the naturally fracture networks. The purpose of this study is to map the fracture intensity distribution in the basement reservoir using Continuous Fracture Modeling (CFM) method. CFM method applies the basic concepts of neural network in finding a relationship between well data with seismic data in order to build a model of fracture intensity. The Formation Micro Imager (FMI) interpretation data is used to identify the presence of fracture along the well as dip angle and dip azimuth. This indicator will be laterally populated in 3D grid model. Several seismic attribute which are generated from seismic data is used as a guidance to populate fracture intensity in the model. The results from the model were validated with Drill Stem Test (DST) data. Zones of high fracture intensity on the model correlates positively with the presence of fluid in accordance with DST data.

  10. 3D gravity inversion and uncertainty assessment of basement relief via Particle Swarm Optimization (United States)

    Pallero, J. L. G.; Fernández-Martínez, J. L.; Bonvalot, S.; Fudym, O.


    Nonlinear gravity inversion in sedimentary basins is a classical problem in applied geophysics. Although a 2D approximation is widely used, 3D models have been also proposed to better take into account the basin geometry. A common nonlinear approach to this 3D problem consists in modeling the basin as a set of right rectangular prisms with prescribed density contrast, whose depths are the unknowns. Then, the problem is iteratively solved via local optimization techniques from an initial model computed using some simplifications or being estimated using prior geophysical models. Nevertheless, this kind of approach is highly dependent on the prior information that is used, and lacks from a correct solution appraisal (nonlinear uncertainty analysis). In this paper, we use the family of global Particle Swarm Optimization (PSO) optimizers for the 3D gravity inversion and model appraisal of the solution that is adopted for basement relief estimation in sedimentary basins. Synthetic and real cases are illustrated, showing that robust results are obtained. Therefore, PSO seems to be a very good alternative for 3D gravity inversion and uncertainty assessment of basement relief when used in a sampling while optimizing approach. That way important geological questions can be answered probabilistically in order to perform risk assessment in the decisions that are made.

  11. A method for evaluating basement exhumation histories from closure age distributions of detrital minerals

    Energy Technology Data Exchange (ETDEWEB)

    Lovera, Oscar M. [Department of Earth and Space Sciences and Institute of Geophysics and Planetary Physics, University of California, Los Angeles (United States); Grove, Marty [Department of Earth and Space Sciences and Institute of Geophysics and Planetary Physics, University of California, Los Angeles (United States); Kimbrough, David L. [Department of Geological Sciences, San Diego State University, San Diego, California (United States); Abbott, Patrick L. [Department of Geological Sciences, San Diego State University, San Diego, California (United States)


    We have developed a two-dimensional, thermokinetic model that predicts the closure age distributions of detrital minerals from pervasively intruded and differentially exhumed basement. Using this model, we outline a method to determine the denudation history of orogenic regions on the basis of closure age distributions in synorogenic to postorogenic forearc strata. At relatively high mean denudation rates of 0.5 km m.y.-1 sustained over millions of years, magmatic heating events have minimal influence upon the age distributions of detrital minerals such as K-feldspar that are moderately retentive of radiogenic Ar. At lower rates, however, the effects of batholith emplacement may be substantial. We have applied the approach to detrital K-feldspars from forearc strata derived from the deeply denuded Peninsular Ranges batholith (PRB). Agreement of the denudation history deduced from the detrital K-feldspar data with thermochronologic constraints from exposed PRB basement lead us to conclude that exhumation histories of magmatic arcs should be decipherable solely from closure age distributions of detrital minerals whose depositional age is known. (c) 1999 American Geophysical Union.

  12. Metasomatic tourmalinite formation along basement-cover decollements, Orobic Alps, Italy (United States)

    Slack, J.F.; Passchier, C.W.; Zhang, J.S.


    Cryptocrystalline tourmalinites that occur discontinuously for ???30 km along basement-cover de??collements of the Orohic Alps (Italy) formed by the metasomatism of aluminous cataclasites derived from Permian conglomerates and/or feldspathic sandstones. Using Al as an immobile element monitor, calculations show that the majority of tourmalinites in the region formed through the addition of moderate to significant amounts of B, Mg, Na, Sr, and Be, and the loss of moderate to significant Mn, Ca, K, P, Rb, Ba, and Cr; minor Si, Ti, V, light REE, and Eu also were lost. Data tor relatively immobile Al, Zr, Th, Sc, Nb, and heavy REE indicate that, on average, these tourmalinites formed through ???12% net mass loss assuming an original conglomerate protolith, or through ???7% net mass loss assuming a sandstone protolith. The B and other introduced constituents in the tourmalinites were deposited by hydrothermal fluids focused along and near basement-cover de??collements. These fluids, believed to be associated with late Hercynian felsic magmatism, probably are related to fluids that formed the tourmaline-rich U-Mo-Zn deposits at the nearby Novazza mine and the U-Zn deposits at the nearby Val Vedello mine.

  13. Seismicity on Basement Faults Induced by Simultaneous Fluid Injection-Extraction (United States)

    Chang, Kyung Won; Segall, Paul


    Large-scale carbon dioxide (CO2) injection into geological formations increases pore pressure, potentially inducing seismicity on critically stressed faults by reducing the effective normal stress. In addition, poroelastic expansion of the reservoir alters stresses, both within and around the formation, which may trigger earthquakes without direct pore-pressure diffusion. One possible solution to mitigate injection-induced earthquakes is to simultaneously extract pre-existing pore fluids from the target reservoir. To examine the feasibility of the injection-extraction strategy, we compute the spatiotemporal change in Coulomb stress on basement normal faults, including: (1) the change in poroelastic stresses Δ τ _s+fΔ σ _n, where Δ τ _s and Δ σ _n are changes in shear and normal stress. respectively, and (2) the change in pore-pressure fΔ p. Using the model of (J. Geophys. Res. Solid Earth 99(B2):2601-2618, 1994), we estimate the seismicity rate on basement fault zones. Fluid extraction reduces direct pore-pressure diffusion into conductive faults, generally reducing the risk of induced seismicity. Limited diffusion into/from sealing faults results in negligible pore pressure changes within them. However, fluid extraction can cause enhanced seismicity rates on deep normal faults near the injector as well as shallow normal faults near the producer by poroelastic stressing. Changes in seismicity rate driven by poroelastic response to fluid injection-extraction depends on fault geometry, well operations, and the background stressing rate.

  14. OMV Yemen's experience in development drilling of the basement reservoir Habban

    Energy Technology Data Exchange (ETDEWEB)

    Klampfer, Simon [OMV Exploration and Production GmbH, Wien (Austria); Boettcher, Frank [OMV Yemen Exploration and Production (Yemen)


    In 2003 OMV AG took over the activities of PREUSSAG Energie International and became operator of the Yemeni Block S2 (Al Uqlah). Activities concentrated initially an appraising the Khulan reservoir, which was discovered by the Kharwah 1 well. Kharwah 1 was used for long-term testing of a two-meter thick Khulan layer producing a reasonably high and constant oil rate with very little decline. Al Nilam 1 was drilled to prove the economics of the discovery and also to look into the basement. The well was successful and a development plan was submitted to the Yemeni authorities including drilling some 42 wells, constructing field facilities and building an oil exporting pipeline. Up to now some 22 wells have been drilled, encountering a number of technical difficulties. A number of potential performance improvements were examined and tested, i.e. percussion drilling for the top hole section, aerated mud in the second and third section to avoid losses and stabilize the hole and the use of impregnated diamond bits in the basement section. A real breakthrough has not yet been achieved. (orig.)

  15. TMI-2 Reactor Building source term measurements: surfaces and basement water and sediment

    Energy Technology Data Exchange (ETDEWEB)

    McIsaac, C V; Keefer, D G


    Presented in this report are the results of radiochemical and elemental analyses performed on samples collected from the Three Mile Island Unit 2 Reactor Building from August 1979 to December 1983. The quantities of fission products and core materials that were measured on the external surfaces in the Reactor Building or in the water and sediment in its basement are summarized. Recent analysis results for access panels removed from the air cooling assembly and for liquid and particulate samples collected from the Reactor Building sump and reactor coolant drain tank are included in the report. Measurements show that 59% of the /sup 3/H, 2.7% of the /sup 90/Sr, 15% of the /sup 129/I, 20% of the /sup 131/I, and 42% of the /sup 137/Cs originally in the core at the time of the accident could be accounted for outside the core in the Reactor Building. With the exceptions of /sup 90/Sr and /sup 144/Ce, the vast majority of each radionuclide released was found dispersed in the water and sediment in the basement.

  16. Detrital record of initial basement exhumation along the Laramide deformation front, southern Rocky Mountains (United States)

    Bush, Meredith A.; Horton, Brian K.; Murphy, Michael A.; Stockli, Daniel F.


    New geochronological constraints on upper crustal exhumation in the southern Rocky Mountains help delineate the latest Cretaceous-Paleogene history of drainage reorganization and landscape evolution during Laramide flat-slab subduction beneath western North America. Detrital zircon U-Pb results for the Raton basin of southern Colorado and northern New Mexico define the inception of coarse-grained siliciclastic sedimentation and a distinctive shift in provenance, from distal to proximal sources, that recorded shortening-related uplift and unroofing along the Laramide deformation front of the northern Sangre de Cristo Mountains. This Maastrichtian-early Paleocene ( 70-65 Ma) change—from distal foreland accumulation of sediment derived from the thin-skinned Cordilleran (Sevier) fold-thrust belt to coarse-grained sedimentation proximal to a Laramide basement block uplift—reflects cratonward (eastward) deformation advance and reorganization of drainage systems that supplied a large volume of Paleocene-lower Eocene sediments to the Gulf of Mexico. The timing of unroofing along the eastern deformation front is synchronous with basement-involved shortening across the interior of the Laramide province, suggesting abrupt wholesale uplift rather than a systematic inboard advance of deformation. The growth and infilling of broken foreland basins within the interior and margins of the Laramide province had a significant impact on continental-scale drainage systems, as several ponded/axial Laramide basins trapped large volumes of sediment and induced reorganization of major source-to-sink sediment pathways.

  17. Comparison among GPR measurements and ultrasonic tomographies with different inversion strategies applied to the basement of an ancient egyptian sculpture. (United States)

    Sambuelli, Luigi; Bohm, Gualtiero; Capizzi, Patrizia; Cardarelli, Ettore; Cosentino, Pietro; D'Onofrio, Laurent; Marchisio, Mario


    By the late 2008 one of the most important pieces of the "Museo delle Antichità Egizie" in Turin, the sculpture of the Pharaoh with god Amun, was planned to be one of the masterpieces of a travelling exhibition in Japan. The "Fondazione Museo delle Antichità Egizie di Torino", managing the museum, was concerned with the integrity of the basement of the statue which actually presents visible signs of restorations dating back to the early IXX century. The questions put by the museum managers were to estimate the internal extension of some visible fractures, to search for unknown internal ones and to provide information about the overall mechanical strength of the basement. In order to tackle the first and second questions a GPR reflection survey of the basement along three sides was performed and the results were assembled in a 3D rendering. As far as the third question is concerned, two parallel, horizontal ultrasonic 2D tomographies across the basement were made with a source-receiver layout able to acquire, for each section, 723 ultrasonic signals correspondent to different transmitter and receiver positions. The ultrasonic tomographic data were inverted using different software based upon different algorithms. The obtained velocity images were then compared with the GPR results and with the visible joints on the basement. A critical analysis of the comparisons is finally presented.

  18. Tectonic inheritage from adjacent basement, north of the Campos Basin; Heranca tectonica no embasamento adjacente no norte da Bacia de Campos

    Energy Technology Data Exchange (ETDEWEB)

    Ferroni, Felipe R. [Universidade Estadual Paulista (UNESP), Rio Claro, SP (Brazil); Castro, Joel C. de [Universidade Estadual Paulista (UNESP), Rio Claro, SP (Brazil). Inst. de Geociencias e Ciencias Exatas. Dept. de Geologia Aplicada; Souza, Iata A. de; Castro, Joel C. de [Universidade Estadual Paulista (UNESP), Rio Claro, SP (Brazil). Inst. de Geociencias e Ciencias Exatas


    The evolution of the Atlantic Brazilian basins is a target of researches since the firth discovery of oil deposits. With the advance of the geophysical methods the understanding of the structures in depth became possible. The objective of this paper is to determine if the adjacent basement in the north of Campos Basin has significant influence in the identification of areas that can contain hydrocarbons. Therefore, lineaments had been extracted with SRTM images of continental basement and the main alignment was correlated with gravimetric anomalies map and seismic data. Eight levels on seismic data had been interpreted (basement, top rift, shallow water Albian, Albian, mid-Oligocene and mid-Miocene). In all levels were identified a fault normal system, which cut sediments since basement until the Recent. The main direction of the basement is NE-SW, and the alignments formed for basin basement faults coincide with this direction, what indicates that the system is active and also genetically related. (author)

  19. Giving your heart to pathology. (United States)

    Klaassen, Jim


    Jim KIaassen recently joined Axiom Veterinary Laboratories as a clinical pathologist. During his career, Dr Klaassen has worked in small animal practice, lectured in clinical pathology, undertaken preclinical research and held senior roles in commercial veterinary laboratories in the USA, including as chief medical officer of Antech Diagnostics.



    Knezevic R. Milan; Andjelic S. Gordana; Knezevic M. Milena


    A retrospective overview of systemic disorders which might be associated with dental pathology is made. They are grouped as follows: (a) congenital dental developmental disorders, (b) chromosomal anomalies, (c) radiations, (d) immune disorders, (e) intoxications, (f) neurological alterations, (g) gastrointestinal diseases, (h) osteodystrophy and associated conditions, (i) skin diseases, (j) metabolic and endocrine disorders, (k) craniofacial malformation syndromes and other congenital g...

  1. The "Shaken Baby" syndrome: pathology and mechanisms. (United States)

    Squier, Waney


    The "Shaken Baby" syndrome (SBS) is the subject of intense controversy; the diagnosis has in the past depended on the triad of subdural haemorrhage (SDH), retinal haemorrhage and encephalopathy. While there is no doubt that infants do suffer abusive injury at the hands of their carers and that impact can cause catastrophic intracranial damage, research has repeatedly undermined the hypothesis that shaking per se can cause this triad. The term non-accidental head injury has therefore been widely adopted. This review will focus on the pathology and mechanisms of the three physiologically associated findings which constitute the "triad" and are seen in infants suffering from a wide range of non-traumatic as well as traumatic conditions. "Sub" dural bleeding in fact originates within the deep layers of the dura. The potential sources of SDH include: the bridging veins, small vessels within the dura itself, a granulating haemorrhagic membrane and ruptured intracranial aneurysm. Most neuropathologists do not routinely examine eyes, but the significance of this second arm of the triad in the diagnosis of Shaken Baby syndrome is such that it merits consideration in the context of this review. While retinal haemorrhage can be seen clinically, dural and subarachnoid optic nerve sheath haemorrhage is usually seen exclusively by the pathologist and only rarely described by the neuroradiologist. The term encephalopathy is used loosely in the context of SBS. It may encompass anything from vomiting, irritability, feeding difficulties or floppiness to seizures, apnoea and fulminant brain swelling. The spectrum of brain pathology associated with retinal and subdural bleeding from a variety of causes is described. The most important cerebral pathology is swelling and hypoxic-ischaemic injury. Mechanical shearing injury is rare and contusions, the hallmark of adult traumatic brain damage, are vanishingly rare in infants under 1 year of age. Clefts and haemorrhages in the immediate

  2. Few remarks on some factors in maintaining temperature of basement; Chikashitsu no hoonsei ni oyobosu shoyoin ni kansuru nisan no chiken

    Energy Technology Data Exchange (ETDEWEB)

    Inada, Y. [Ehime University, Ehime (Japan). Faculty of Engineering; Shimasaki, O. [Ehime University, Ehime (Japan); Ueda, T. [Takenaka Corp., Osaka (Japan); Matsumoto, T. [Nissan Construction Co. Ltd., Tokyo (Japan); Sugi, G.


    Noticing on temperature maintaining effect of a basement, three types of full scale model basements were used to measure temperature change in the surrounding ground and rooms in the basement and discuss effects of ground temperature variation on the basement. Thermal property values were derived on the surrounding ground affecting the temperature maintainability of the basement, and temperature analysis was performed on a model assuming the basement to discuss effects of difference in size occupying under the ground on change in room temperatures. Then, assuming a case of using heat insulating materials in the basement, discussions were given on the consumed energy required for air conditioning. Underground temperature has its change to decrease as the ground depth increases throughout a year, and particularly at depths greater than 50 cm, no daily temperature change can be seen. Because of this effect, the greater the underground occupying size in the basement, the smaller the temperature change. Distributions of heat diffusion rate, heat capacity, and heat conductivity can be estimated by deriving water content ratio distribution. When air conditioning is carried out in the basement, applying the heat insulating materials on the inner side of a room is more effective. Energy conservation may be expected because the room temperature is stabilized. 9 refs., 27 figs., 4 tabs.

  3. Palaeoproterozoic U Pb SHRIMP zircon age from basement rocks in Bangladesh: A possible remnant of the Columbia supercontinent (United States)

    Hossain, Ismail; Tsunogae, Toshiaki; Rajesh, Hariharan M.; Chen, Bin; Arakawa, Yoji


    We present new U-Pb SHRIMP zircon geochronological data for basement rocks in Bangladesh, and discuss the relationship with the formation of the Columbia supercontinent. Euhedral zircons from a diorite sample yield a concordia age of 1730 ± 11 Ma, which is interpreted as the crystallization age. The Palaeoproterozoic age of the examined basement rock and the common occurrences of similar ˜1.7-Ga geologic units in the Central Indian Tectonic Zone and Meghalaya-Shillong Plateau in Indian Shield suggest their apparent continuation. This, together with the occurrence of similar ˜1.7-Ga geologic units in the Albany-Fraser belt in Australia and East Antarctica, are used to suggest that the basement rocks in Bangladesh formed towards the final stages of the assembly of the Columbia supercontinent.


    Directory of Open Access Journals (Sweden)

    Vijaya Sheela


    Full Text Available INTRODUCTION: The placental development is an essential step in developing effective strategies or the prediction of various maternal and fetal medical and developmental problems . Oxygen transfer and nutrients to the fetus will be actively regulated by the placenta . AIM AND OBJECTIVE: To study morphological changes of placenta in Intrauterine growth Retardation and to correlate morphological changes of placenta with fetal outcome . MATERIALS AND METHODS: Placental tissue samples were obtained from 50 pregnancies complicated by IUGR and 50 normal uncomplicated pregnancies with gestational age between 28 to 42 weeks attending King George hospital Visakhapatnam . INCLUSIVE CRITERIA : An IUGR fetuses whose estimated fetal weight less than those in 10 th percentile are included in the study . Birth weight percentiles were determined by previously published normal curves . EXCLUSIVE CRITERIA: fetuses with known syndromes , chromosomal anomalies and twins . For all patients included in the data set gestational age was estimated from the last menstrual period or early ultra - sonogram before the 12 th week of gestation . The final data set was composed of 50pregnancies complicated by IUGR and APGAR scores . Because preeclampsia is an important maternal factor associated with IUGR , these cases were further divided into t wo subgroups according to presence of hypertension . Samples were taken both from vaginal deliveries and caesarean sections . All the placentas were examined by pathologists . The placentas were weighed . For each case one or two samples from the umbilical cor ds , extra placental membrane , and parenchyma were taken . Gross pathological findings were confirmed by histology . Histological data included are ischemic necrosis , decidual vascularity , acute chorioamni oni tis , fibrinoid necrosis and choriangiosis . Appropriate statistical parameters were used . Chi - square test was conducted to compare placental pathological changes

  5. Biomineralization and matrix vesicles in biology and pathology. (United States)

    Golub, Ellis E


    In normal healthy individuals, mineral formation is restricted to specialized tissues which form the skeleton and the dentition. Within these tissues, mineral formation is tightly controlled both in growth and development and in normal adult life. The mechanism of calcification in skeletal and dental tissues has been under investigation for a considerable period. One feature common to almost all of these normal mineralization mechanisms is the elaboration of matrix vesicles, small (20-200 nm) membrane particles, which bud off from the plasma membrane of mineralizing cells and are released into the pre-mineralized organic matrix. The first crystals which form on this organic matrix are seen in and around matrix vesicles. Pathologic ectopic mineralization is seen in a number of human genetic and acquired diseases, including calcification of joint cartilage resulting in osteoarthritis and mineralization of the cardiovasculature resulting in exacerbation of atherosclerosis and blockage of blood vessels. Surprisingly, increasing evidence supports the contention that the mechanisms of soft tissue calcification are similar to those seen in normal skeletal development. In particular, matrix vesicle-like membranes are observed in a number of ectopic calcifications. The purpose of this review is to describe how matrix vesicles function in normal mineral formation and review the evidence for their participation in pathologic calcification.

  6. Nature of the Yucatan Block Basement as Derived From Study of Granitic Clasts in the Impact Breccias of Chicxulub Crater (United States)

    Vera-Sanchez, P.; Rebolledo-Vieyra, M.; Perez-Cruz, L.; Urrutia-Fucugauchi, J.


    The tectonic and petrologic nature of the basement of the Yucatan Block is studied from analyses of basement clasts present in the impact suevitic breccias of Chicxulub crater. The impact breccias have been sampled as part of the drilling projects conducted in the Yucatan peninsula by Petroleos Mexicanos, the National University of Mexico and the Chicxulub Scientific Drilling Project. Samples analyzed come mainly from the Yaxcopoil-1, Tekax, and Santa Elena boreholes, and partly from Pemex boreholes. In this study we concentrate on clasts of the granites, granodiorites and quartzmonzonites in the impact breccias. We report major and trace element geochemical and petrological data, which are compared with data from the granitic and volcanic rocks from the Maya Mountains in Belize and from the Swannee terrane in Florida. Basement granitic clasts analyzed present intermediate to acidic sub-alkaline compositions. Plots of major oxides (e.g., Al2O3, Fe2O3, TiO2 and CaO) and trace elements (e.g., Th, Y, Hf, Nb and Zr) versus silica allow separation of samples into two major groups, which can be compared to units in the Maya Mountains and in Florida basement. The impact suevitic breccia samples have been affected by alteration likely related to the hydrothermal processes associated with the crater melt sheet. Cloritization, seritization and fenitization alterations are recognized, due to the long term hydrothermalism. Krogh et al. (1993) reported U-Pb dates on zircons from the suevitic breccias, which gave dates of 545 +/- 5 Ma and 418 +/- 6 Ma, which were interpreted in terms of the deep granitic metamorphic Yucatan basement. The younger date correlates with the age for the Osceola Granite and the St. Lucie metamorphic complex of the Swannee terrane in the Florida peninsula. The intrusive rocks in the Yucatan basement may be related to approx. 418 Ma ago collisional event in the Late Silurian.

  7. The offshore basement of Perú: Evidence for different igneous and metamorphic domains in the forearc (United States)

    Romero, Darwin; Valencia, Kiko; Alarcón, Pedro; Peña, Daniel; Ramos, Victor A.


    As a result of new studies carried out in the offshore of Perú during the exploration and hydrocarbon evaluation of the forearc basins, new U-Pb SHRIMP and TIMS in zircons and some Ar-Ar data were obtained in the metamorphic and igneous basement. The understanding of this basement was critical to evaluate different hypotheses that have been proposed for the tectonic evolution of pre-Andean crust of Perú. Recent research performed in the basement rocks of the Marañón Massif in northern Perú, claimed that west of this area was a basement-free region in the Paleozoic, where the arc and forearc were developed in a mafic quasi-oceanic crust. However, petrographic studies and new preliminary ages indicate, for the first time, the nature and age of this sialic basement. Reconnaissance studies were performed in several offshore islands, as the Las Hormigas de Afuera Island west of Lima, and Macabí and Lobera islands along the edge of the continental platform. These data were complemented with the studies of some cutting samples obtained in recent exploration wells in northern Perú. The results of the present work show two large crustal domains in the Peruvian offshore forearc. A northern domain contains late Paleozoic igneous rocks that appear to be the southern offshore continuation of the Amotape-Tahuin block, which is interpreted as the southernmost remnant of the Laurentia Alleghenian orogen. The central offshore domain, known as the Paracas High, corresponds to the outer shelf high of previous studies. It contains orthogneisses of Grenville-age, probably recrystallized during an Ordovician magmatic episode. The new results show that the central offshore of Perú is an extension of the Grenville-age basement affected by Famatinian, early Paleozoic magmatism, well exposed in the southern domain in the Arequipa Massif along the coast of southern Perú.

  8. Potential links between porphyry copper deposits and exhumed metamorphic basement complexes in northern Chile (United States)

    Cooper, Frances; Docherty, Alistair; Perkins, Rebecca


    Porphyry copper deposits (PCDs) are typically associated with magmatic arcs in compressional subduction zone settings where thickened crust and fractionated calc-alkaline magmas produce favourable conditions for copper mineralisation. A classic example is the Eocene-Oligocene PCD belt of Chile, the world's leading copper producing country. In other parts of the world, older late Cretaceous to early Tertiary PCDs are found in regions of former subduction-related magmatism that have undergone subsequent post-orogenic crustal extension, such as the Basin and Range province of western North America, and the Eurasian Balkan-Carpathian-Dinaride belt. In the Basin and Range there is a striking correlation between the location of many PCDs and exhumed metamorphic core complexes (isolated remnants of the middle to lower crust exhumed during extensional normal faulting). This close spatial relationship raises questions about the links between the two. For example, are their exhumation histories related? Could the presence of impermeable metamorphic rocks at depth affect and localise mineralising fluids? In Chile there appears to be a similar spatial relationship between PCDs and isolated outcrops of exhumed metamorphic basement. In northern Chile, isolated exposures of high-grade metamorphic gneisses and amphibolites are thought to be exhumed remnants of the pre-subduction Proterozoic-Paleozoic continental margin of Gondwana [2], although little is known about when they were exhumed and by what mechanism. For example, the Limón Verde metamorphic complex, exhumed from a depth of ca. 50 km, is situated adjacent to Chuquicamata, the largest open pit copper mine in the world. In northernmost Chile, another metamorphic exposure, the Belén complex, sits close to the Dos Hermanos PCD, a small deposit that is not actively mined. Comprising garnet-bearing gneisses and amphibolites, the Belén is thought to have been exhumed from a depth of ca. 25 km, but when and how is unclear [3

  9. Sulfur isotope evidence for penetration of MVT fluids into igneous basement rocks, southeast Missouri, USA (United States)

    Shelton, K. L.; Burstein, I. B.; Hagni, R. D.; Vierrether, C. B.; Grant, S. K.; Hennigh, Q. T.; Bradley, M. F.; Brandom, R. T.


    Previous studies of galena and sphalerite from Paleozoic MVT deposits in the Viburnum Trend, southeast Missouri documented large variations in δ34S values throughout the ore-forming event. The present study of Cu-Fe-sulfides reveals a similar δ34S variation that reflects two end-member sulfur reservoirs whose relative importance varied both temporally and spatially. More 34S-enriched sulfides (δ34S approaching 25‰) indicate introduction of sulfur from basinal sedimentary sources, whereas more 32S-enriched sulfides (δ34S Precambrian, igneous-hosted FeCu mineralization in southeast Missouri (West and Central Domes of Boss-Bixby) were investigated to elucidate their relationship to Cu-rich MVT orebodies hosted nearby within the overlying Cambrian Bonneterre Dolomite. Mineralization at Boss-Bixby is composed of an early phase of iron oxide deposition followed by Cu-Fe-sulfides. The Central Dome is faulted and its mineralization is more fracture-controlled than the typically podiform ores of the West Dome. The δ34S values of West Dome sulfides are 0.9 to 6.5‰ and pyrite-chalcopyrite indicate a temperature of 525° ± 50 °C. These data indicate an igneous source of sulfur during Precambrian ore deposition. In contrast, δ34S values of Central Dome sulfides are 9.4 to 20.0‰ and pyrite-chalcopyrite indicate temperatures of 275° ± 50 °C. Similar δ34S values are obtained for chalcopyrite from the overlying MVT deposits. We speculate that deeply circulating, basin-derived MVT fluids mobilized sulfur and copper from the underlying igneous basement and redeposited them in overlying Curich MVT orebodies, as well as overprinting earlier Precambrian sulfides of the Central Dome with a later, Paleozoic MVT sulfur isotope signature. Many models for MVT fluid circulation in the Midcontinent region of North America assume that igneous basement rocks are an impermeable boundary, but in southeast Missouri, evidence exists for structurally controlled MVT fluid movement

  10. A model of basement structure from magnetic anomalies of the Bombay High oil-field west of India

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, D.G.

    The bathymetry map reveals a gradual deepen- ing of the seabed from about 50 m in the east to 80-90 m in the west (Fig.3). The seabed is largely of even topography with low-amplitude but con- spicuous, rises in the north and local depressions in the south... depth of 2.0 km; in the south it extends to 3.5 km. Basement relief of > 1 km is observed in the south over distances of 2-6 km. This relief could be due to faulting of the basement in a WSW-ENE direction. The Murud Depression (Fig.7) with a deeper...

  11. Assessment of Pollutant Spread from a Building Basement with three Ventilation Systems

    CERN Document Server

    Koffi, Juslin


    Ventilation aims at providing a sufficient air renewal for ensuring a good indoor air quality (IAQ), yet building energy policies are leading to adapting various ventilation strategies minimising energy losses through air renewal. A recent IAQ evaluation campaign in French dwellings shows important pollution of living spaces by VOCs such as formaldehyde, acetaldehyde or hexanal, particularly in buildings equipped with a garage. Besides, radon emission from soil is a subject of concern in many countries. Several studies are done to understand its release mode and deal with the spread of this carcinogen gas. This paper aims to experimentally assess a contaminant spread from a house basement using mechanical exhaust and balanced ventilation systems, and natural ventilation.

  12. Thermal history of the Pan-African basement under the Jurassic Marib-Shabwa Basin, Yemen (United States)

    Rice, A. Hugh N.; Schneider, David; Veeningen, Resi; Grasemann, Bernhard; Decker, Kurt


    Pan-African tectonism within the Arabian Nubian Shield in Yemen is very poorly known. New drill-cores from the Marib-Shabwa Basin (Habban oil field) from central Yemen penetrated 600 m into the pre-Jurassic crystalline basement, providing a unique opportunity to extend our understanding of Pan-African events in Yemen. The cores were obtained some 80 km NE of the exposure limit of the Al Bayda Terrane, which lies SE of Sana'a. This terrane, which has no direct correlative in the ANS further north in Saudi Arabia, comprises deformed greenschist facies acid to basic volcanic rocks later witnessing acid to basic magmatism and has been previously interpreted as a Pan-African island arc complex with a basement component. Ophiolite fragments are common, both within the terrane and at its margins (sutures). To the north lies the Abas Gneiss Terrane and to the south the Al Mahfid Gneiss Terrane; both consist of older pre-Pan-African crystalline basement rocks. Geochemistry of a red, undeformed granite from the drill core indicates an A-type composition. LA-ICPMS U-Pb analysis of granite zircons gave two concordant age populations: 628.3 ± 3.1 Ma (large & small zircons) and 604.9 ± 2.0 Ma (intermediate sized zircons). The former age is interpreted as the time of crystallization, within the range of other A-type Younger Granites in the ANS, and the latter age as constraining lower temperature dissolution-reprecipitation of zircon, due to hydrothermal fluids or melt remobilization. Nd Tdm model ages for two granite samples from the drill core both gave ages of 1.24 Ga, within the range of the Al Bayda Terrane (1.2-2.5 Ga) and outside the range of the adjacent Palaeoproterozoic gneissic terranes (1.7-2.3 Ga, Abas Gneiss Terrane; 1.8-3.0 Ga, Al Mahfid Gneiss Terrane). Thus it seems certain that the Al Bayda Terrane extends at least 80 km to the NE of its present surface exposure. Rb-Sr biotite ages from the granite indicate closure through ~300°C at 593 Ma, indicating fast

  13. New insights in prolactin: pathological implications. (United States)

    Bernard, Valérie; Young, Jacques; Chanson, Philippe; Binart, Nadine


    Prolactin is a hormone that is mainly secreted by lactotroph cells of the anterior pituitary gland, and is involved in many biological processes including lactation and reproduction. Animal models have provided insights into the biology of prolactin proteins and offer compelling evidence that the different prolactin isoforms each have independent biological functions. The major isoform, 23 kDa prolactin, acts via its membrane receptor, the prolactin receptor (PRL-R), which is a member of the haematopoietic cytokine superfamily and for which the mechanism of activation has been deciphered. The 16 kDa prolactin isoform is a cleavage product derived from native prolactin, which has received particular attention as a result of its newly described inhibitory effects on angiogenesis and tumorigenesis. The discovery of multiple extrapituitary sites of prolactin secretion also increases the range of known functions of this hormone. This Review summarizes current knowledge of the biology of prolactin and its receptor, as well as its physiological and pathological roles. We focus on the role of prolactin in human pathophysiology, particularly the discovery of the mechanism underlying infertility associated with hyperprolactinaemia and the identification of the first mutation in human PRLR.

  14. Pathological fear of cot death. (United States)

    Weightman, H; Dalal, B M; Brockington, I F


    Cot death (sudden infant death syndrome) is one of the most common causes of death in the first year of life. Four cases with a pathological fear of cot death are presented. All the patients were depressed and in 2 cases the fear of cot death had an obsessional quality. In all cases there were complications during pregnancy (miscarriage, threatened abortion, recurrent vomiting in last trimester). In 1 case, the patient knew 3 mothers who had suffered cot deaths; in another, the infant was gravely ill in the neonatal period. Pathological fear of cot death can be recognised by the presence of two central features - overvigilance and excessive nocturnal checking of the baby's breathing. Therapeutic interventions are discussed.

  15. Lung Pathology in Antiphospholipid Syndrome

    Directory of Open Access Journals (Sweden)

    T. M. Reshetnyak


    Full Text Available Functional lesions of organs depend on the size of a diseased vessel and frequently require the use of intensive therapy methods. The commonest manifestation of antiphospholipid syndrome (APS is deep vein thrombosis of the leg and pulmonary thromboembolism (PTE.Objective: to estimate the frequency of lung lesions in primary APS (PAPS, secondary (in the presence of systemic lupus erythematosus (SLE and catastrophic APS and to assess a relationship between lung pathology and other clinical and laboratory manifestations of the disease.Subjects and methods. The study covered 372 patients followed up at the Institute of Rheumatology, Russian Academy of Medical Sciences, since 1990, of whom 290 and 82 patients had SLE and PAPS, respectively. Among the 290 patients with SLE, there were 96 males and 194 females. At the moment of the study, the patients’ age was 31.2±11.1 years and the duration of the disease was 8.6±7.2 years. The group of patients with PAPS comprised 20 males and 62 females. Their mean age was 35.6±9.9 years and the duration of the disease was 11.9±8.5 years. Thrombotic events were verified only by instrumental studies. Lung pathology was instrumentally confirmed; all the patients underwent lung X-ray study, if required, scintigraphy and computed tomography.Results. Lung lesion associated with the pathology of vessels was revealed in 28% of the examined patients (105/372. There were prevalent patients with PTE, followed by the development of lung infarcts, which was present in 96 (91% of the 105 patients with pulmonary vascular pathology. Autopsy revealed pulmonary microangiopathy was in 12 patients, which was concurrent with focal pneumonia in 7 of them, with pneumonitis and exudative pleuritis in 5. Hemorrhagic alveolitis detected at autopsy in combination with occlusions of the pulmonary arterioles was in 3 patients who had been diagnosed as having thromboembolism of small branches of the pulmonary artery. Thrombosis of the

  16. Innovations in teaching plant pathology. (United States)

    Schumann, G L


    The teaching environment for plant pathology is changing in both positive and negative ways. Teaching expectations are increasing and resources are decreasing, but recent educational research and instructional technology offer new approaches to meet these challenges. Plant pathologists are teaching courses that may attract new students to the discipline or at least improve agricultural awareness. The Internet offers rapid access to information and images for both students and instructors. Instructional technology provides new tools for classroom presentations, communication with students, reaching new audiences, and distance learning, but using these new tools to enhance learning requires skilled and creative instructors. In the past, many plant pathology instructors worked in relative isolation, but new communication technologies and publishing opportunities for teaching scholarship should improve the sharing of instructional resources and methods.

  17. Pathological Gambling in Parkinson's Disease

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Linnet, Jakob; Thomsen, Kristine Rømer

    Pathological Gambling in Parkinson’s Disease Mette Buhl Callesen, Jakob Linnet, Kristine Rømer Thomsen, Albert Gjedde, Arne Møller PET Center, Aarhus University Hospital and Center of Functionally Integrative Neuroscience, Aarhus University.   The neurotransmitter dopamine is central to many...... aspects of human functioning, e.g., reward, learning, and addiction, including Pathological Gambling (PG), and its loss is key to Parkinson’s Disease (PD). PD is a neurodegenrative disorder caused by progressive loss of dopamine-producing cells in the midbrain [1]. One type of treatment of PD symptoms...... is medication that binds to dopamine receptors in the brain, i.e., dopamine agonists [1]. Unfortunately, for some PD patients a very serious side effect to this specific kind of treatment is developing PG. PG is an Impulse Control Disorder characterized by recurrent maladaptive behavior associated with personal...

  18. Can the Metamorphic Basement of Northwestern Guatemala be Correlated with the Chuacús Complex? (United States)

    Cacao, N.; Martens, U.


    The Chuacús complex constitutes a northward concave metamorphic belt that stretches ca. 150 km south of the Cuilco-Chixoy-Polochic (CCP) fault system in central and central-eastern Guatemala. It represents the basement of the southern edge of the Maya block, being well exposed in the sierra de Chuacús and the sierra de Las Minas. It is composed of high-Al metapelites, amphibolites, quartzofeldspathic gneisses, and migmatites. In central Guatemala the Chuacús complex contains ubiquitous epidote-amphibolite mineral associations, and local relics of eclogite reveal a previous high-pressure metamorphic event. North of the CCP, in the Sierra de Los Cuchumatanes area of western Guatemala, metamorphic rocks have been considered the equivalent of the Chuacús complex and hence been given the name Western Chuacús group, These rocks, which were intruded by granitic rocks and later mylonitized, include chloritic schist and gneiss, biotite-garnet schist, migmatites, and amphibolites. No eclogitic relics have been found within metamorphic rocks in northwestern Guatemala. Petrographic analyses of garnet-biotite schist reveal abundant retrogression and the formation of abundant zeolite-bearing veins associated with intrusion. Although metamorphic conditions in the greenschist and amphibolite facies are similar to those in the sierra de Chuacús, the association with deformed intrusive granites is unique for western Guatemala. Hence a correlation with metasediments intruded by the Rabinal granite in the San Gabriel area of Baja Verapaz seems more feasible than a correlation with the Chuacús complex. This idea is supported by reintegration of the Cenozoic left-lateral displacement along the CCP, which would place the metamorphic basement of western Guatemala north of Baja Verapaz, adjacent to metasediments intruded by granites in the San Gabriel-Rabinal area.

  19. Applications of aeromagnetic data to detect the Basement Tectonics of Eastern Yemen region

    Directory of Open Access Journals (Sweden)

    Ahmed S. Abu El-Ata


    Full Text Available The present study aims to throw light on the tectonic implications concerned with the distribution of the sedimentary sequence belts and the related basement complex zones, as well as to differentiate between the causative sources (contacts, dykes and faults of Eastern Yemen region. The total intensity aeromagnetic map of the study area was first corrected by the application of the Reduction To the magnetic pole (for low latitude areas. The visual inspection of the RTP magnetic map defines a rapid change in the subsurface geologic conditions in the form of lithologic characters and tectonic inferences. On the other hand, this map showed different anomalies of varying frequencies and amplitudes that revealed various causative sources, as well as varying compositions and depths. At the interpretation stage, various techniques and software tools are available for extracting the geologic information from the data concerned. The magnetic fields of shallow sources can be separated from those of deeper causatives, using two processes known as power spectrum transformation and matched band pass filtering. Three methods for locating magnetic sources (Magnitude of Horizontal Gradients (HGM, the analytical signals (AS and the local wavenumbers (LW in three dimensions and identifying the properties of their sources indicated that, the area was affected by some intrusions at various depths in sill or dyke forms, almost oriented in the NW–SE, NE–SW, E–W and N–S trends. Tectonically, the area is highly affected by the tectonics related to the Arabian Sea, Gulf of Aden and Red Sea. It is affecting both the basement and sedimentary rocks, dividing the study area into several faulted blocks.

  20. Integrating aeromagnetic and Landsat™ 8 data into subsurface structural mapping of Precambrian basement complex (United States)

    Kayode, John Stephen; Nawawi, M. N. M.; Abdullah, Khiruddin B.; Khalil, Amin E.


    The integration of Aeromagnetic data and remotely sensed imagery with the intents of mapping the subsurface geological structures in part of the South-western basement complex of Nigeria was developed using the PCI Geomatica Software. 2013. The data obtained from the Nigerian Geological Survey Agency; was corrected using Regional Residual Separation of the Total Magnetic field anomalies enhanced, and International Geomagnetic Reference Field removed. The principal objective of this study is, therefore, to introduce a rapid and efficient method of subsurface structural depth estimate and structural index evaluation through the incorporation of the Euler Deconvolution technique into PCI Geomatica 2013 to prospect for subsurface geological structures. The shape and depth of burial helped to define these structures from the regional aeromagnetic map. The method enabled various structural indices to be automatically delineated for an index of between 0.5 SI and 3.0 SI at a maximum depth of 1.1 km that clearly showed the best depths estimate for all the structural indices. The results delineate two major magnetic belts in the area; the first belt shows an elongated ridge-like structure trending mostly along the NorthNortheast-SouthSouthwest and the other anomalies trends primarily in the Northeast, Northwest, Northeast-Southwest parts of the study area that could be attributed to basement complex granitic intrusions from the tectonic history of the area. The majority of the second structures showed various linear structures different from the first structure. Basically, a significant offset was delineated at the core segment of the study area, suggesting a major subsurface geological feature that controls mineralisation in this area.

  1. The character and significance of basement rocks of the southern Molucca Sea region (United States)

    Hall, Robert; Nichols, Gary; Ballantyne, Paul; Charlton, Tim; Ali, Jason

    Pre-Neogene basement rocks in the southern Molucca Sea region include ophiolitic rocks, arc volcanic rocks and continental rocks. The ophiolitic complexes are associated with arc and forearc igneous and sedimentary rocks. They are interpreted as the oldest parts of the Philippine Sea Plate with equivalents in the ridges and plateaux of the northern Philippine Sea. In the Molucca Sea region igneous components include rocks with a "supra-subduction zone" character, bonintic volcanic rocks and basic volcanic rocks with a "within-plate" character; "MORB-type" rocks are rare or absent. The ophiolitic rocks are overlain by Upper Cretaceous and Eocene sedimentary and volcanic rocks. Plutonic rocks of island arc origin which intrude the ophiolites yield Late Cretaceous radiometric ages and amphibolites with ophiolitic protoliths yield Eocene ages. The "supra-subduction zone" ophiolites are speculated to have originated during a mid-Cretaceous plate reorganization event. For the Late Cretaceous and Eocene the present-day Marianas arc and forearc provides an attractive model. Volcanic rocks from the basement of Morotai, western Halmahera and much of Bacan. These also have an island arc character and are probably of Late Cretaceous-Paleogene age. Both the arc volcanic rocks and the ophiolitic complexes are overlain by shallow water Eocene limestones and an Oligocene rift sequence including basaltic pillow lavas and volcaniclastic turbidites. The distribution of the Eocene-Oligocene sequences indicate pre-Mid/Late Eocene amalgamation of the ophiolitic and arc terranes. Mid Eocene-Oligocene extension appears to be synchronous with opening of the central West Philippine Basin. Continental crust probably arrived in this region in the Late Paleogene-Early Neogene, either due to collision of the Australian margin with Pacific arc-ophiolite terranes or by terrane movement along the Sorong Fault Zone.

  2. Comparison of radon levels in building basements and above- ground floors

    Energy Technology Data Exchange (ETDEWEB)

    Cazula, C.; Campos, M.; Mazzilli, B. [IPEN/CNEN-SP, Sao Paulo (Brazil)


    Radon-222, a decay product of Ra-226, is a natural radioactive noble gas that can be found in soil, water and air. Radon and its short-lived decay products in the atmosphere are the most important contributors to human exposure from natural sources. Radon is recognized as the second most significant risk for lung cancer after tobacco smoking. The World Health Organization established a concentration of 100 Bq m{sup -3} for radon in air, in order to limit its hazards. The main source of radon exposition indoors comes from Ra-226, a decay product of the U-238 natural series, present in rocks and soils underneath the building and, to a lesser extent, in the building materials. The dynamics of radon production in rocks and soil and its subsequent indoors emanation is quite complex. It is controlled by factors such as soil permeability and water content, meteorological variability, building foundation characteristics and the usual positive differential pressure between the soil and the indoor environment. This is normally sufficient to bring soil gas from the ground into the building. Radon gas can enter a building by several mechanisms, but the most significant ones are diffusion and pressure-driven flow from the ground. Usually, cracks and holes in the floor and walls and gaps around service pipes are the main entrance for the radon gas. Studies indicated that indoor radon concentration present significant variation on the basement, ground floor and upper floors. The aim of this study is to determine the radon levels in building basements and above- ground floors in the city of Sao Paulo. Radon measurements were carried out through the passive method with solid-state nuclear- track detectors (CR-39), because of their simplicity and long-term integrated read-out. The exposure period was, at least, three months, covering one year minimum, in order to determine the seasonal variation of indoor radon concentration. Document available in abstract form only. (authors)

  3. Structural Controls on Groundwater Flow in Basement Terrains: Geophysical, Remote Sensing, and Field Investigations in Sinai

    KAUST Repository

    Mohamed, Lamees


    An integrated [very low frequency (VLF) electromagnetic, magnetic, remote sensing, field, and geographic information system (GIS)] study was conducted over the basement complex in southern Sinai (Feiran watershed) for a better understanding of the structural controls on the groundwater flow. The increase in satellite-based radar backscattering values following a large precipitation event (34 mm on 17–18 January 2010) was used to identify water-bearing features, here interpreted as preferred pathways for surface water infiltration. Findings include: (1) spatial analysis in a GIS environment revealed that the distribution of the water-bearing features (conductive features) corresponds to that of fractures, faults, shear zones, dike swarms, and wadi networks; (2) using VLF (43 profiles), magnetic (7 profiles) techniques, and field observations, the majority (85 %) of the investigated conductive features were determined to be preferred pathways for groundwater flow; (3) northwest–southeast- to north–south-trending conductive features that intersect the groundwater flow (southeast to northwest) at low angles capture groundwater flow, whereas northeast–southwest to east–west features that intersect the flow at high angles impound groundwater upstream and could provide potential productive well locations; and (4) similar findings are observed in central Sinai: east–west-trending dextral shear zones (Themed and Sinai Hinge Belt) impede south to north groundwater flow as evidenced by the significant drop in hydraulic head (from 467 to 248 m above mean sea level) across shear zones and by reorientation of regional flow (south–north to southwest–northeast). The adopted integrated methodologies could be readily applied to similar highly fractured basement arid terrains elsewhere. © 2015 Springer Science+Business Media Dordrecht

  4. Insulin dysfunction and Tau pathology

    Directory of Open Access Journals (Sweden)

    Noura eEl Khoury


    Full Text Available The neuropathological hallmarks of Alzheimer's disease (AD include senile plaques of β-amyloid (Aβ peptides (a cleavage product of the Amyloid Precursor Protein, or APP and neurofibrillary tangles (NFT of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF. NFT pathology is important since it correlates with the degree of cognitive impairment in AD.Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99% is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease.Insulin dysfunction, manifested by diabetes mellitus (DM might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM and type 2 diabetes (T2DM are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment.Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting on Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

  5. Medical discourse in pathological anatomy. (United States)

    Moskalenko, R; Tatsenko, N; Romanyuk, A; Perelomova, O; Moskalenko, Yu


    The paper is devoted to the peculiarities of medical discourse in pathological anatomy as coherent speech and as a linguistic correlate of medical practice taking into account the analysis of its strategies and tactics. The purpose of the paper is to provide a multifaceted analysis of the speech strategies and tactics of pathological anatomy discourse and ways of their implementation. The main strategies of medical discourse in pathological anatomy are an anticipating strategy, a diagnosing strategy and an explaining one. The supporting strategies are pragmatic, conversational and a rhetorical one. The pragmatic strategy is implemented through contact establishing tactics, the conversational one - with the help of control tactics, the rhetorical one - with the help of attention correction tactics. The above mentioned tactics and strategies are used in the distinguishing of major, closely interrelated strategies: "the contact strategy" (to establish contact with a patient's relatives - phatic replicas of greeting and addressing) and "the strategy of explanation" (used in the practice of a pathologist for a detailed explanation of the reasons of a patient's death). The ethic aspect of speech conduct of a doctor-pathologist is analyzed.

  6. Simulation of the steady-state transport of radon from soil into houses with basements under constant negative pressure

    Energy Technology Data Exchange (ETDEWEB)

    de Oliveira Loureiro, C.


    A theoretical model was developed to simulate this phenomenon, under some specific assumptions. The model simulates: the generation and decay of radon within the soil; its transport throughout the soil due to diffusion and convection induced by the pressure disturbance applied at a crack in the basement; its entrance into the house through the crack; and the resultant indoor radon concentration. The most important assumptions adopted in the model were: a steady-state condition; a house with a basement; a geometrically well-defined crack at the wall-floor joint in the basement; and a constant negative pressure applied at the crack in relation to the outside atmospheric pressure. Two three-dimensional finite-difference computer programs were written to solve the mathematical equations of the model. The first program, called PRESSU, was used to calculate: the pressure distribution within the soil as a result of the applied disturbance pressure at the crack; and the resultant velocity distribution of the soil gas throughout the soil matrix. The second program, called MASTRA, was used to: solve the radon mass-transport equation, and to calculate the concentration distribution of radon in the soil gas within the whole soil; and to calculate the entry rate of radon through the crack into the basement, and the final indoor radon concentration. A parametric sensitivity analysis performed on the model, revealed several features of the mechanisms involved in the transport of radon into the house. 84 refs., 66 figs., 16 tabs.

  7. Analysis of ABCC6: elucidation of the molecular pathology of pseudoxanthoma elasticum

    NARCIS (Netherlands)

    X. Hu (Xiaofeng)


    textabstractThis thesis describes research to elucidate the molecular pathology of pseudoxanthoma elasticum (PXE), from phenotype to genotype. PXE is an autosomally inherited disorder of connective tissue, affecting the skin, Bruch's membrane of the eye, and cardiovascular system. The most apparent

  8. Personality dimensions and disorders in pathological gambling

    DEFF Research Database (Denmark)

    Odlaug, Brian Lawrence; Schreiber, Liana R N; Grant, Jon E


    This review presents the most current research in personality dimensions and disorders with respect to pathological gambling.......This review presents the most current research in personality dimensions and disorders with respect to pathological gambling....

  9. Congruence Couple Therapy for Pathological Gambling (United States)

    Lee, Bonnie K.


    Couple therapy models for pathological gambling are limited. Congruence Couple Therapy is an integrative, humanistic, systems model that addresses intrapsychic, interpersonal, intergenerational, and universal-spiritual disconnections of pathological gamblers and their spouses to shift towards congruence. Specifically, CCT's theoretical…

  10. Extensive renovation the pathology of heritage building

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn


    The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures.......The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures....

  11. Extensive renovation the pathology of heritage buildings

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn


    The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures.......The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures....

  12. Gravity analysis of the Precambrian basement topography associated with the northern boundary of Ghadames Basin (southern Tunisia) (United States)

    Dhaoui, Mohamed; Gabtni, Hakim; Jallouli, Chokri; Jleilia, Ali; Mickus, Kevin Lee; Turki, Mohamed Moncef


    Gravity data were analyzed to determine the structural development of the northern boundary of the Ghadames Basin in southern Tunisia. The Ghadames Basin which also occurs in eastern Algeria and northwestern Libya is one of the most prolific hydrocarbon producers in North Africa with several of the largest oil fields occurring along its northern boundary. The Ghadames Basin was formed during a series of tectonic events ranging from the Early Paleozoic to the Early Cenozoic. These tectonic events produced a basin in southern Tunisia that has a complex basement configuration which is not completely known. A residual gravity anomaly map constructed using polynomial trend surfaces, and vertical and horizontal gravity derivative maps indicate that the northern boundary contains a series of maxima and minima anomalies that trend in two prominent directions: northeast-southwest and east-west. The horizontal and vertical derivative gravity anomaly maps indicate that the width of the basement structures range between 10 and 20 km in width. Three-dimensional (3D) Euler deconvolution and 3D forward modeling constrained by well data, one seismic reflection profile and remote sensing data confirm the width of the basement structures and indicates that the depth of basin varies between 1.5 and 5 km, with deeper sections in general more numerous in the southern sections of the boundary. The gravity analysis constrained by the seismic reflection profile and well data implies that the basement topography may have been formed during the Pan African and/or late Mesozoic rifting. However, additional seismic reflection and well data are needed to confirm this conclusion. The discovery of the numerous basement structures suggests that there may exist additional hydrocarbon traps within the northern boundary of the Ghadames Basin.

  13. Heterogeneity of groundwater storage properties in the critical zone of Irish metamorphic basement from geophysical surveys and petrographic analyses (United States)

    Comte, Jean-Christophe; Cassidy, Rachel; Caulfield, John; Nitsche, Janka; Ofterdinger, Ulrich; Wilson, Christopher


    Weathered/fractured bedrock aquifers contain groundwater resources that are crucial in hard rock basement regions for rural water supply and maintaining river flow and ecosystem resilience. Groundwater storage in metamorphic rocks is subject to high spatial variations due to the large degree of heterogeneity in fracture occurrence and weathering patterns. Point measurements such as borehole testing are, in most cases, insufficient to characterise and quantify those storage variations because borehole sampling density is usually much lower than the scale of heterogeneities. A suite of geophysical and petrographic investigations was implemented in the weathered/fractured micaschist basement of Donegal, NW Ireland. Electrical Resistivity Tomography provided a high resolution 2D distribution of subsurface resistivities. Resistivity variations were transferred into storage properties (i.e. porosities) in the saturated critical zone of the aquifer through application of a petrophysical model derived from Archie's Law. The petrophysical model was calibrated using complementary borehole gamma logging and clay petrographic analysis at multi-depth well clusters distributed along a hillslope transect at the site. The resulting distribution of porosities shows large spatial variations along the studied transect. With depth, porosities rapidly decrease from about a few % in the uppermost, highly weathered basement to less than 0.5% in the deep unweathered basement, which is encountered at depths of between 10 and 50m below the ground surface. Along the hillslope, porosities decrease with distance from the river in the valley floor, ranging between 5% at the river to less than 1% at the top of the hill. Local traces of regional fault zones that intersect the transect are responsible for local increases in porosity in relation to deeper fracturing and weathering. Such degrees of spatial variation in porosity are expected to have a major impact on the modality of the response of

  14. A case of Biateral Extensive Persistent Pupillary Membranes with Amblyopia and Cataract

    Directory of Open Access Journals (Sweden)

    Sibel Kocabeyoğlu


    Full Text Available Persistent pupillary membrane represents a congenital remnant of the anterior tunica vasculosa lentis. It can be associated with other ocular pathologies. These membranes can cause deprivation or anisometropic amblyopia. The choice of treatment depends on the patient’s age and the characteristics of the membranes. In this paper, we report the findings in a 21-year-old female patient with bilateral persistent pupillary membranes, amblyopia, and cataract. (Turk J Ophthalmol 2013; 43: 70-2

  15. 42 CFR 493.853 - Condition: Pathology. (United States)


    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  16. Telescoping phenomenon in pathological gambling

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Mooney, Marc E


    The course of pathological gambling (PG) in women has been described as having a later age of initiation but a shorter time to problematic gambling ("telescoped"). This study examined evidence for telescoping and its relationship with comorbidities. Seventy-one treatment-seeking individuals with PG...... underwent a diagnostic interview to examine gambling behaviors, age at initiation of gambling, and time from initiation to meeting criteria for PG. The women had a higher mean age at gambling initiation compared with that of the men (mean [SD] age, 31.3 [13.0] years, compared with 22.4 [7.9] years; p = 0...

  17. Basement nappes on the NE boundary the Ossa-Morena Zone (SW Iberian Variscides) (United States)

    Romao, Jose Manuel; Ribeiro, Antonio; Munha, Jose; Ribeiro, Luisa


    basement nappe is considerable, at least 5 to 10 km, considering the presence of mafic granulites included in intermediate granulites, both retrograded into the amphibolite facies, in the SW Bioucas and in the NE Olalhas klippe, resting on top of the lower-grade poly-metamorphic Cadomian assemblages. Geological data summarized above confirm the presence of Cadomian basement nappes that were reactivated under a thick-skinned thrust regime during the Variscan cycle; therefore, implying a poly-orogenic evolution for the studied tectonic units. TBCSZ represents a Cadomian suture that was initially reactivated during Lower Paleozoic intercontinental rifting, later evolving to transpressive intra-plate flower structure during the Upper Paleozoic Variscan convergence phase. It is concluded that thick-skinned tectonic regime by Variscan reactivation of Cadomian basement is a major element in the geodynamic evolution in the internal zones of SW European Variscides and of the Variscan Orogen in general terms.

  18. Timing and conditions of regional metamorphism and crustal shearing in the granulite facies basement of south Namibia: Implications for the crustal evolution of the Namaqualand metamorphic basement in the Mesoproterozoic (United States)

    Bial, Julia; Büttner, Steffen; Appel, Peter


    Granulite facies basement gneisses from the Grünau area in the Kakamas Domain of the Namaqua-Natal Metamorphic Province in south Namibia show high-grade mineral assemblages, most commonly consisting of garnet, cordierite, sillimanite, alkali feldspar and quartz. Cordierite + hercynitic spinel, and in some places quartz + hercynitic spinel, indicate granulite facies P-T conditions. The peak assemblage equilibrated at 800-850 °C at 4.0-4.5 kbar. Sillimanite pseudomorphs after kyanite1 and late-stage staurolite and kyanite2 indicate that the metamorphic record started and ended within the stability field of kyanite. Monazite in the metamorphic basement gneisses shows a single-phase growth history dated as 1210-1180 Ma, which we interpret as the most likely age of the regional metamorphic peak. This time coincides with the emplacement of granitic plutons in the Grünau region. The ∼10 km wide, NW-SE striking Grünau shear zone crosscuts the metamorphic basement and overprints high-temperature fabrics. In sheared metapelites, the regional metamorphic peak assemblage is largely obliterated, and is replaced by synkinematic biotite2, quartz, alkali feldspar, sillimanite and cordierite or muscovite. In places, gedrite, staurolite, sillimanite and green biotite3 may have formed late- or post-kinematically. The mylonitic mineral assemblage equilibrated at 590-650 °C at 3.5-5.0 kbar, which is similar to a retrograde metamorphic stage in the basement away from the shear zone. Monazite cores in two mylonite samples are similar in texture and age (∼1200 Ma) to monazite in metapelites away from the shear zone. Chemically distinct monazite rims indicate a second growth episode at ∼1130-1120 Ma. This age is interpreted to date the main deformation episode along the Grünau shear zone and the retrograde metamorphic stage seen in the basement. The main episode of ductile shearing along the Grünau shear zone took place 70-80 million years after the thermal peak metamorphism

  19. The Basement of the Andes: the Gondwana-Laurentia Connections Revisited (United States)

    Ramos, V. A.


    The research performed in the last decade in the basement of the Andes have shown that the Precambrian and Paleozoic rocks have recorded a series of igneous and metamorphic events through time. These episodes can be grouped in discrete orogenic events, which have different paleogeographic distribution and intensity. The first and most important orogenic event is widely distributed along the margin and correspond to the Sunsas-Grenville orogen. Evidence of metamorphism and associated magmatic rocks are found from Colombia to the southernmost Patagonia. This episode produced the amalgamation of Amazonia, Pampia and Patagonia, among other cratonic blocks, to form Rodinia. The Rodinia break-up leaved several cratonic blocks accreted in the Gondwana side, such as Marañón, Arequipa, and Antofalla, although the generalized extension of this period produced crustal attenuation, rifted basins, and limited oceanic realms during late Proterozoic times. The Brasiliano-Pampean orogeny reamalgamated these blocks against the Gondwana margin. A new episode of break-up produced the dispersal of several Gondwanian blocks, separation along some previous sutures, crustal attenuation and magmatism in Late Cambrian times, until the new amalgamation occurred in Middle Late Ordovician times. These processes led to the Famatinian orogeny when metamorphism and arc magmatism was widely spread along the continental margin, as seen in Chibcha, Marañón, Arequipa and Sierras Pampeanas. Besides the re-accretion of some parautochthonous terranes, new exotic blocks were derived from Laurentia, such as the Cuyania terrane, which finally collided against the Andean proto-margin at ~ 460 Ma to form the Argentine Precordillera and surrounding regions. Late accretion in Early to Middle Devonian times of Chilenia and related terranes formed most of the basement of Central Andes. Final collision between Laurentia and Gondwana in the Late Carboniferous - Early Permian times to form the Alleghanides

  20. Orogenic gold mineralisation hosted by Archaean basement rocks at Sortekap, Kangerlussuaq area, East Greenland (United States)

    Holwell, D. A.; Jenkin, G. R. T.; Butterworth, K. G.; Abraham-James, T.; Boyce, A. J.


    A gold-bearing quartz vein system has been identified in Archaean basement rocks at Sortekap in the Kangerlussuaq region of east Greenland, 35 km north-northeast of the Skaergaard Intrusion. This constitutes the first recorded occurrence of Au mineralisation in the metamorphic basement rocks of east Greenland. The mineralisation can be classified as orogenic style, quartz vein-hosted Au mineralisation. Two vein types have been identified based on their alteration styles and the presence of Au mineralisation. Mineralised type 1 veins occur within sheared supracrustal units and are hosted by garnet-bearing amphibolites, with associated felsic and ultramafic intrusions. Gold is present as native Au and Au-rich electrum together with arsenopyrite and minor pyrite and chalcopyrite in thin alteration selvages in the immediate wall rocks. The alteration assemblage of actinolite-clinozoisite-muscovite-titanite-scheelite-arsenopyrite-pyrite is considered to be a greenschist facies assemblage. The timing of mineralisation is therefore interpreted as being later and separate event to the peak amphibolite facies metamorphism of the host rocks. Type 2 quartz veins are barren of mineralisation, lack significant alteration of the wall rocks and are considered to be later stage. Fluid inclusion microthermometry of the quartz reveals three separate fluids, including a high temperature ( T h = 300-350 °C), H2O-CO2-CH4 fluid present only in type 1 veins that in interpreted to be responsible for the main stage of Au deposition and sulphidic wall rock alteration. It is likely that the carbonic fluids were actually trapped at temperatures closer to 400 °C. Two other fluids were identified within both vein types, which comprise low temperature (100-200 °C) brines, with salinities of 13-25 wt% eq. NaCl and at least one generation of low salinity aqueous fluids. The sources and timings of the secondary fluids are currently equivocal but they may be related to the emplacement of

  1. Plumbotectonic aspects of polymetallic vein mineralization in Paleozoic sediments and Proterozoic basement of Moravia (Czech Republic) (United States)

    Slobodník, Marek; Jacher-Śliwczyńska, Katarzyna; Taylor, Matthew C.; Schneider, Jens; Dolníček, Zdeněk


    A regional isotopic study of Pb and S in hydrothermal galenas and U-Pb and S in potential source rocks was carried out for part of Moravia, Czech Republic. Two major generations of veins, (syn-) Variscan and post-Variscan, are defined based on the Pb-isotope system together with structural constraints (local structures and regional trends). The Pb-isotopic compositions of galena plot in two distinct populations with outliers in 206Pb/204Pb-207Pb/204Pb space. Galena from veins hosted in greywackes provides a cluster with the lowest Pb-Pb ratios: 206Pb/204Pb = 18.15-18.27, 207Pb/204Pb = 15.59-15.61, 208Pb/204Pb = 38.11-38.23. Those hosted in both limestones and greywackes provide the second cluster: 206Pb/204Pb = 18.37-18.44, 207Pb/204Pb = 15.60-15.63, 208Pb/204Pb = 38.14-38.32. These clusters suggest model Pb ages as Early Carboniferous and Triassic-Jurassic, the latter associated with MVT-like deposits. Two samples from veins hosted in Proterozoic rocks lie outside the two clusters: in metagranitoid (206Pb/204Pb = 18.55, 207Pb/204Pb = 15.64, 208Pb/204Pb = 38.29) and in orthogneiss (206Pb/204Pb = 18.79, 207Pb/204Pb = 15.73, 208Pb/204Pb = 38.54). The results from these two samples suggest an interaction of mineralizing fluids with the radiogenic Pb-rich source (basement?). The values of δ34S suggest the Paleozoic host rocks (mostly -6.7 to +5.2‰ CDT) as the source of S for hydrothermal sulfides (mostly -4.8 to +2.5‰ CDT). U-Pb data and Pb isotope evolutionary curves indicate that Late Devonian and Early Carboniferous sediments, especially siliciclastics, are the general dominant contributor of Pb for galena mineralization developed in sedimentary rocks. Plumbotectonic mixing occurred, it is deduced, only between the lower and the upper crust (the latter involving Proterozoic basement containing heterogeneous radiogenic Pb), without any significant input from the mantle. It is concluded that in the Moravo-Silesian and Rhenohercynian zones (including proximal

  2. 2.9-1.9 Ga paleoalterations of Archean granitic basement of the Franceville basin (Gabon) (United States)

    Mouélé, Idalina Moubiya; Dudoignon, Patrick; El Albani, Abderrazak; Meunier, Alain; Boulvais, Philippe; Gauthier-Lafaye, François; Paquette, Jean-Louis; Martin, Hervé; Cuney, Michel


    The Archean granitoids in the Kiéné area, Gabon, are overlained by the Paleoproterozoic sediments of the Franceville basin (2.1 Ga). The basin is known for its high-grade uranium deposits among which some have been forming natural nuclear fission reactors. Most of the studies were dedicated to the FA-FB Paleoproterozoic sediments hosting these uranium deposits. Little is known on the Archean basement itself and specifically on the hydrous alteration events it experienced before and after the sediment deposition. The present work is focused on their petrographical, mineralogical and geochemical characterization. Dating the successive alteration events has been attempted on altered monazite crystals. Rocks in different alteration states have been sampled from eight drill cores crosscutting the Archean - Paleoproterozoic unconformity. The Archean granitoids observed in the deepest levels exhibit typical petrographical features of a propylitic alteration while they are intensely illitized up to the unconformity. The propylitic alteration is mainly pervasive but the original texture of the granitoïds is conserved in spite of the formation of new minerals: Mg-chlorite, allanite and epidote forming a typical paragenesis. The illitic alteration is much more invasive near the unconformity. The illitization process leads to the replacement of feldspars and the corrosion of quartz crysals by an illitic matrix while the ferromagnesian minerals are pseudomorphosed by a Fe-chlorite + phengite + hematite assemblage. The final fluid-rock interaction step is marked by fissural deposits of calcite and anhydrite. The δ13C isotopic data show that the fissural carbonates precipitated from diagenetic fluids enriched carbon products deriving from the maturation of organic matter. The U-Pb isotopic analyzes performed on monazite crystals have dated three distinct events: 3.0-2.9 Ga (magmatic), 2.6 Ga (propylitic alteration) and 1.9 Ga (diagenetic illitization). The calculation of

  3. Eocene extensional exhumation of basement and arc rocks along southwesternmost Peru, Central Andes. (United States)

    Noury, Mélanie; Bernet, Matthias; Sempéré, Thierry


    The overthickened crust of the current Central Andes is commonly viewed as the result of tectonic shortening. However, in the present-day terrestrial forearc and arc of southwesternmost Peru, crustal thickness increases from 30 km along the coastline to >60 km below the active arc, whereas the upper crust exhibits little to no evidence of crustal shortening and, in constrast, many extensional features. How (and when) crustal overthickness was acquired in this region is thus little understood. Because crustal overthickening often results in extensional collapse and/or significant erosion, here we address this issue through a regional-scale study of exhumation using fission-track thermochronology. The limited fission-track data previously available in the area suggested that exhumation began during the Mesozoic. In this study, we present new apatite and zircon fission-track data obtained along the current terrestrial forearc of southwesternmost Peru. This relatively restricted area presents the interest of providing extensive outcrops of Precambrian to Ordovician basement and Early Jurassic to Late Cretaceous arc plutons. In order to compare the chronology of exhumation of these units, we performed extensive sampling for fission-track dating, as well as structural mapping. Our results indicate that the basement rocks and Jurassic plutons that crop out in the Arequipa region, where the crust is now >50 km-thick, experienced a rapid cooling through the 240-110°C temperature range between ~65 and ~35 Ma. This period of rapid exhumation coincided in time with the accumulation of terrestrial forearc deposits (the Lower Moquegua Group), that exhibit many syn-sedimentary extensional features and are bounded by conspicuous normal faults, specifically along the region where intense activity of the main arc between ~90 and ~60 Ma had led to voluminous magma emplacement. This close succession of (1) intense magmatic activity and (2) regional-scale exhumation associated with

  4. Pathologic pancreatic endocrine cell hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Debra Ouyang; Deepti Dhall; Run Yu


    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge.Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels,and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

  5. Dopamine Agonists and Pathologic Behaviors

    Directory of Open Access Journals (Sweden)

    Brendan J. Kelley


    Full Text Available The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson’s disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.

  6. Fibroadenomas: Sonographic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sung; Choi, Hye Young; Kim, Eun Ah; Lee, Sun Wha; Sung, Soon Hee [Ewha Womans University, Seoul (Korea, Republic of)


    To correlate sonographic appearance and histopathologic findings of fibroadenomas. Forty-one biopsy-proven fibroadenomas were retrospectively evaluate for sonographic-pathologic correlation. The fibroadenomas were histologically classified into sclerotic, myxoid, glandular and mixed type. The stromal cellularity and fibrosis were also classified into mild and severe. The internal echotexture and posterior acoustic enhancement of mass in ultrasonogram were correlated with histopathologic findings. The pathologic types of fibroadenomas were sclerotic in sixteen, myxoid in thirteen, and glandular or mixed in each of six cases. Most of the sclerotic type showed hypoechoic internal echotexture (68.8%) and myxoid and glandular types showed isoechoic internal echotexture (84.6%, 83.3% respectively). The hypoechoic masses showed 12 cases of mild (75.0%) and 4 cases of severe (25.0%) in cellularity and 3 cases of mild (18.7%) and 13 cases (81.3%) of sever degree in fibrosis. Most of the myxoid type (77%) showed posterior enhancement, and most of the sclerotic type (87.5%) did not show posterior enhancement on ultrasonogram. Posterior enhancement was absent in 22 cases, in which 4 cases (18.2%) showed mild and 18 cases (81.2%) showed severe degree of fibrosis. Sclerotic type with mild cellularity and severe fibrosis on histopathology showed hypoechogenicity on ultrasonogram; whereas myxoid and glandular types were predominantly isoechoic. Most of the myxoid type showed posterior enhancement. Sclerotic type with mild cellularity and severe fibrosis did not show posterior enhancement.

  7. From biological membranes to biomimetic model membranes

    Directory of Open Access Journals (Sweden)

    Eeman, M.


    Full Text Available Biological membranes play an essential role in the cellular protection as well as in the control and the transport of nutrients. Many mechanisms such as molecular recognition, enzymatic catalysis, cellular adhesion and membrane fusion take place into the biological membranes. In 1972, Singer et al. provided a membrane model, called fluid mosaic model, in which each leaflet of the bilayer is formed by a homogeneous environment of lipids in a fluid state including globular assembling of proteins and glycoproteins. Since its conception in 1972, many developments were brought to this model in terms of composition and molecular organization. The main development of the fluid mosaic model was made by Simons et al. (1997 and Brown et al. (1997 who suggested that membrane lipids are organized into lateral microdomains (or lipid rafts with a specific composition and a molecular dynamic that are different to the composition and the dynamic of the surrounding liquid crystalline phase. The discovery of a phase separation in the plane of the membrane has induced an explosion in the research efforts related to the biology of cell membranes but also in the development of new technologies for the study of these biological systems. Due to the high complexity of biological membranes and in order to investigate the biological processes that occur on the membrane surface or within the membrane lipid bilayer, a large number of studies are performed using biomimicking model membranes. This paper aims at revisiting the fundamental properties of biological membranes in terms of membrane composition, membrane dynamic and molecular organization, as well as at describing the most common biomimicking models that are frequently used for investigating biological processes such as membrane fusion, membrane trafficking, pore formation as well as membrane interactions at a molecular level.

  8. Anatomical pathology is dead? Long live anatomical pathology. (United States)

    Nicholls, John M; Francis, Glenn D


    The standard diagnostic instrument used for over 150 years by anatomical pathologists has been the optical microscope and glass slide. The advent of immunohistochemistry in the routine laboratory in the 1980s, followed by in situ hybridisation in the 1990s, has increased the armamentaria available to the diagnostic pathologist, and this technology has led to changed patient management in a limited number of neoplastic diseases. The first decade of the 21 century has seen an increasing number of publications using proteomic technologies that promise to change disease diagnosis and management, the traditional role of an anatomical pathologist. Despite the plethora of publications on proteomics and pathology, to date there are actually limited data where proteomic technologies do appear to be of greater diagnostic value than the standard histological slide. Though proteomic techniques will become more prevalent in the future, it will need the expertise of an anatomical pathologist to dissect out and validate this added information.

  9. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne


    Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

  10. Microporous Inorganic Membranes as Proton Exchange Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Vichi, F.M. Tejedor-Tejedor, M.I. Anderson, Marc A


    Porous oxide electrolyte membranes provide an alternative approach to fabricating proton exchange membrane fuel cells based on inorganic materials. This study focused on elucidating the properties of these inorganic membranes that make them good electrolyte materials in membrane electrode assemblies; in particular, we investigated several properties that affect the nature of proton conductivity in these membranes. This report discusses our findings on the effect of variables such as site density, amount of surface protonation and surface modification on the proton conductivity of membranes with a fixed pore structure under selected conditions. Proton conductivities of these inorganic membranes are similar to conductivities of nafion, the polymeric membrane most commonly used in low temperature fuel cells.

  11. Review: Protein folding pathology in domestic animals

    Institute of Scientific and Technical Information of China (English)



    Fibrillar proteins form structural elements of cells and the extracellular matrix. Pathological lesions of fibrillar microanatomical structures, or secondary fibrillar changes in globular proteins are well known. A special group concerns histologically amorphous deposits, amyloid. The major characteristics of amyloid are: apple green birefringence after Congo red staining of histological sections, and non-branching 7-10nm thick fibrils on electron microscopy revealing a high content of cross beta pleated sheets. About 25 different types of amyloid have been characterised. In animals, AA-amyloid is the most frequent type. Other types of amyloid in animals represent: AIAPP (in cats), AApoAⅠ, AApoAⅡ, localised AL-amyloid, amyloid in odontogenic or mammary tumors and amyloid in the brain. In old dogs Aβ and in sheep APrPsc-amyloid can be encountered. AA-amyloidosis is a systemic disorder with a precursor in blood, acute phase serum amyloid A (SAA). In chronic inflammatory processes AA-amyloid can be deposited. A rapid crystallization of SAA to amyloid fibrils on small beta-sheeted fragments, the ‘amyloid enhancing factor' (AEF), is known and the AEF has been shown to penetrate the enteric barrier. Amyloid fibrils can aggregate from various precursor proteins in vitro in particular at acidic pH and when proteolytic fragments are formed. Molecular chaperones influence this process. Tissue data point to amyloid fibrillogenesis in lysosomes and near cell surfaces. A comparison can be made of the fibrillogenesis in prion diseases and in enhanced AA-amyloidosis. In the reactive form, acute phase SAA is the supply of the precursor protein, whereas in the prion diseases, cell membrane proteins form a structural source. AI3-amyloid in brain tissue of aged dogs showing signs of dementia forms a canine counterpart of senile dementia of the Alzheimer type (ccSDAT) in man. Misfolded proteins remain potential food hazards. Developments concerning prevention of amyloidogenesis

  12. Protein folding pathology in domestic animals

    Institute of Scientific and Technical Information of China (English)

    GRUYS Erik


    Fibrillar proteins form structural elements of cells and the extracellular matrix. Pathological lesions of fibrillar microanatomical structures, or secondary fibrillar changes in globular proteins are well known. A special group concerns histologically amorphous deposits, amyloid. The major characteristics of amyloid are: apple green birefringence after Congo red staining of histological sections, and non-branching 7-10 nm thick fibrils on electron microscopy revealing a high content of cross beta pleated sheets. About 25 different types of amyloid have been characterised. In animals,AA-amyloid is the most frequent type. Other types of amyloid in animals represent: AIAPP (in cats), AApoAⅠ, AApoAⅡ,localised AL-amyloid, amyloid in odontogenic or mammary tumors and amyloid in the brain. In old dogs Aβ and in sheep APrPsc-amyloid can be encountered. AA-amyloidosis is a systemic disorder with a precursor in blood, acute phase serum amyloid A (SAA). In chronic inflammatory processes AA-amyloid can be deposited. A rapid crystallization of SAA to shown to penetrate the enteric barrier. Amyloid fibrils can aggregate from various precursor proteins in vitro in particular at acidic pH and when proteolytic fragments are formed. Molecular chaperones influence this process. Tissue data point to amyloid fibrillogenesis in lysosomes and near cell surfaces. A comparison can be made of the fibrillogenesis in prion diseases and in enhanced AA-amyloidosis. In the reactive form, acute phase SAA is the supply of the precursor protein,whereas in tho prion diseases, cell membrane proteins form a structural source. Aβ-amyloid in brain tissue of aged dogs showing signs of dementia forms a canine counterpart of senile dementia of the Alzheimer type (ccSDAT) in man. Misfolded proteins remain potential food hazards. Developments concerning prevention of amyloidogenesis and therapy of amyloid deposits are shortly commented.

  13. ADAMs family and relatives in cardiovascular physiology and pathology. (United States)

    Zhang, Pu; Shen, Mengcheng; Fernandez-Patron, Carlos; Kassiri, Zamaneh


    A disintegrin and metalloproteinases (ADAMs) are a family of membrane-bound proteases. ADAM-TSs (ADAMs with thrombospondin domains) are a close relative of ADAMs that are present in soluble form in the extracellular space. Dysregulated production or function of these enzymes has been associated with pathologies such as cancer, asthma, Alzheimer's and cardiovascular diseases. ADAMs contribute to angiogenesis, hypertrophy and apoptosis in a stimulus- and cell type-dependent manner. Among the ADAMs identified so far (34 in mouse, 21 in human), ADAMs 8, 9, 10, 12, 17 and 19 have been shown to be involved in cardiovascular development or cardiomyopathies; and among the 19 ADAM-TSs, ADAM-TS1, 5, 7 and 9 are important in development of the cardiovascular system, while ADAM-TS13 can contribute to vascular disorders. Meanwhile, there remain a number of ADAMs and ADAM-TSs whose function in the cardiovascular system has not been yet explored. The current knowledge about the role of ADAMs and ADAM-TSs in the cardiovascular pathologies is still quite limited. The most detailed studies have been performed in other cell types (e.g. cancer cells) and organs (nervous system) which can provide valuable insight into the potential functions of ADAMs and ADAM-TSs, their mechanism of action and therapeutic potentials in cardiomyopathies. Here, we review what is currently known about the structure and function of ADAMs and ADAM-TSs, and their roles in development, physiology and pathology of the cardiovascular system.

  14. The Basement of the Central Andes: The Arequipa and Related Terranes (United States)

    Ramos, Victor A.


    The basement of the Central Andes provides insights for the dispersal of Rodinia, the reconstruction of Gondwana, and the dynamics of terrane accretion along the Pacific. The Paleoproterozoic Arequipa terrane was trapped during collision between Laurentia and Amazonia in the Mesoproterozoic. Ultrahigh-temperature metamorphism correlates with the collapse of the Sunsás-Grenville orogen after 1000 Ma and is related to slab break-off and dispersal of Rodinia. The Antofalla terrane separated in the Neoproterozoic, forming the Puncoviscana basin. Its closure was coeval with the collision of the eastern Sierras Pampeanas. The rift-drift transitions of the early Paleozoic clastic platform showed a gradual younging to the north, in agreement with counterclockwise rotation based on paleomagnetic data of Antofalla. North of Arequipa arc magmatism and high-grade metamorphism are linked to collision of the Paracas terrane in the Ordovician, during the Famatinian orogeny in the Sierras Pampeanas. The early Paleozoic history of the Arequipa massif is explained by a backarc, which further south changed to open oceanic conditions and subsequent collision. The Antofalla terrane reaccreted to the continental margin by the late Ordovician. These accretions and subsequent separations during the Mesoproterozoic, Neoproterozoic early Cambrian, and late Cambrian middle Ordovician are explained by changes in absolute motion of the Gondwana supercontinent during plate global reorganization.

  15. Imaging Quaternary glacial deposits and basement topography using the transient electromagnetic method for modeling aquifer environments (United States)

    Simard, Patrick Tremblay; Chesnaux, Romain; Rouleau, Alain; Daigneault, Réal; Cousineau, Pierre A.; Roy, Denis W.; Lambert, Mélanie; Poirier, Brigitte; Poignant-Molina, Léo


    Aquifer formations along the northern shore of the Saint-Lawrence River in Quebec (Canada) mainly consist of glacial and coastal deposits of variable thickness overlying Precambrian bedrock. These deposits are important because they provide the main water supply for many communities. As part of a continuing project aimed at developing an inventory of the groundwater resources in the Charlevoix and Haute-Côte-Nord (CHCN) regions of the province of Quebec in Canada, the central loop transient electromagnetic (TEM) method was used to map the principal hydrogeological environments in these regions. One-dimensional smooth inversion models of the TEM soundings have been used to construct two-dimensional electrical resistivity sections, which provided images for hydrogeological validation. Electrical contour lines of aquifer environments were compared against available well logs and Quaternary surface maps in order to interpret TEM soundings. A calibration table was achieved to represent common deposits and basements. The calibration table was then exported throughout the CHCN region. This paper presents three case studies; one in the Forestville site, another in the Les Escoumins site and the other in the Saint-Urbain site. These sites were selected as targets for geophysical surveys because of the general lack of local direct hydrogeological data related to them.

  16. Impact of climate on groundwater recharge in the crystalline basement rocks aquifer of Northern Ghana (United States)

    Koffi, K. V.


    Water is the cornerstone of human life and for all economic developments. West Africa and specifically Ghana are no exception to this reality.Northern Ghana is characterized by a semi-arid climate, with prolonged dry season (7 months of very few rainfall) leading to the drying up of many rivers and streams. In addition, rainfall is highly variable in space and time. Therefore, surface water is unreliable and insufficient to meet the water demands for socio-economic development in this area. As a result, the area is heavily dependent on groundwater for domestic water supply as well as for dry season irrigation of vegetables (cash crops).However, aquifers in northern Ghana are dominantly the hard rock type (Crystalline basement rock). This aquifer has no primary porosity and may not be able to sustain the increasing demand on the resource. Further, climate change may worsen the situation as recharge is dependent on rainfall in northern Ghana. Therefore, it is important to understand exactly how climate change will impact on recharge to the groundwater for sustainable development and management of the resource.Previous groundwater studies in Northern Ghana barely analyzed the combined impacts of Climate change on the recharge to the groundwater. This research is aimed at determining the current relationship between groundwater recharge and rainfall and to use the relationships to determine the impacts of changes in climate on the groundwater recharge. The results will inform plans and strategies for sustainably managing groundwater resources in Ghana and the Volta basin.

  17. Trace-element composition of Chicxulub crater melt rock, K/T tektites and Yucatan basement (United States)

    Hildebrand, A. R.; Gregoire, D. C.; Attrep, M., Jr.; Claeys, P.; Thompson, C. M.; Boynton, W. V.


    The Cretaceous/Tertiary (K/T) boundary Chicxulub impact is the best preserved large impact in the geologic record. The Chicxulub crater has been buried with no apparent erosion of its intracrater deposits, and its ejecta blanket is known and is well preserved at hundreds of localities globally. Although most of the molten material ejected from the crater has been largely altered, a few localities still preserve tektite glass. Availability of intra- and extracrater impact products as well as plausible matches to the targeted rocks allows the comparison of compositions of the different classes of impact products to those of the impacted lithologies. Determination of trace-element compositions of the K/T tektites, Chicxulub melt rock, and the targeted Yucatan silicate basement and carbonate/evaporite lithologies have been made using instrumental neutron activation analysis (INAA) and inductively coupled plasma mass spectrometry (ICP-MS). Some sample splits were studied with both techniques to ensure that inter-laboratory variation was not significant or could be corrected. The concentration of a few major and minor elements was also checked against microprobe results. Radiochemical neutron activation analysis (RNAA) was used to determine Ir abundances in some samples.

  18. Anaerobic membrane bioreactors: Are membranes really necessary?

    NARCIS (Netherlands)

    Davila, M.; Kassab, G.; Klapwijk, A.; Lier, van J.B.


    Membranes themselves represent a significant cost for the full scale application of anaerobic membrane bioreactors (AnMBR). The possibility of operating an AnMBR with a self-forming dynamic membrane generated by the substances present in the reactor liquor would translate into an important saving. A

  19. Inversion of Gravity Data for Imaging of a Sediment-basement Interface: A Case Study in the Northwestern Part of Bangladesh (United States)

    Rahman, Md. Mahbubar; Ullah, Shaikh Enayet


    Gravity data collected by the Geological Survey of Bangladesh are processed and interpreted for imaging of a sediment-basement interface over the northwestern part of Bangladesh. The observed gravity data are processed for discriminating gravitational fields contributed subtly from the shallow basement topographic feature with the twelve nodal piecewise cubic polynomial-based finite-element approach. In spectral analysis, the presence of a widely spread shallow basement feature has been detected and interpretation of gravity data using a two-dimensional gravity inversion technique indicates that its depth ranges from 0.041 km to 0.570 km relative to ground surface. In the northern part of the study area, the inferred basement configuration shows a general depression of the basement in the Takurgaon-Panchagar and Lalmonirhat districts and reaches a maximum depth of about 0.570 km. In the Nilphamari district and its southwestern part, the basement occurs at the most shallow depth due to its upliftment. However, the estimated sediment-basement interface depths are compared with the borehole and other geophysical interpretative information and are found to be consistent.

  20. Pathology of hepatic iron overload

    Institute of Scientific and Technical Information of China (English)

    Yves Deugnier; Bruno Turlin


    Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful (1) to assess prognosis by grading fibrosis and seeking for associated lesions and (2) to guide the etiological diagnosis, especially when no molecular marker is available.Then, the type of liver siderosis (parenchymal, mesenchymal or mixed) and its distribution throughout the lobule and the liver are useful means for suggesting its etiology: HLA-linked hemochromatosis gene (HFE) hemochromatosis or other rare genetic hemochromatosis,nonhemochromatotic genetic iron overload (ferroportin disease, aceruloplasminemia), or iron overload secondary to excessive iron supply, inflammatory syndrome,noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

  1. Placental pathology in pregnancy complications. (United States)

    Huppertz, Berthold


    Among pregnancy pathologies preeclampsia and fetal growth restriction are among the leading causes of maternal and perinatal mortality and morbidity. For both syndromes, the etiologies are still unclear in many facets. For the development of preeclampsia the presence of the placenta is a prerequisite, while for FGR a variety of other factors may be decisive. Cases with a combination of FGR and preeclampsia are the most severe cases and need clinical intervention. Studies on such cases have misled scientists and clinicians to hypothesize that a failure of trophoblast invasion is a specific feature of the early onset type of preeclampsia. Recent development in preeclampsia specific biomarkers and the intense use of Doppler ultrasound measurements already in the first trimester of pregnancy has resulted in a new understanding of the pathways leading to preeclampsia or FGR.

  2. Radiologic Imaging of Diaphragmatic Pathologies

    Directory of Open Access Journals (Sweden)

    Hatice Öztürkmen Akay


    Full Text Available We researched the images methods in the evaluation of diaphragmaticpathologies. The study was done with 30 patients (21 males, 9 females. Themedian age of the patients was 36.1 years (Range 1-74 years. Firstly,lateraly and posteroanterior chest X-Ray were done in all patients the otherradiological images were the Barium examination, ultrasonography,computerized tomography and magnetic rezonans imaging. We determineddiaphragmatic pseudotumour in 4 patients, congenital diaphragmatichernia in 6 patients, diaphragmatic paralysis in 2 patients, diaphragmaticelevation in 8 patients, hiatal hernia in 5 patients, and diaphragmaticrupture in 5 patients.Although radiological images were developed all, we believe that thediaphragmatic pathologies should be evaluated with both clinically andradiologically in all patients.

  3. [Ductoscopy for pathologic nipple discharge]. (United States)

    Waaijer, Laurien; van Diest, Paul J; van der Pol, Carmen C; Verolme, Berna; Hennink, Annelies; Witkamp, Arjen J


    Pathologic nipple discharge is a symptom that frequently causes female patients to visit the outpatient breast clinic. In the vast majority of cases, the symptom is caused by a benign intraductal laesion. The options for diagnosis and treatment have long been limited; surgery was not infrequently the treatment of choice. With the advent of breast ductoscopy, a micro-endoscopic procedure, it is possible to visualise abnormalities in the ductal system. Tissue for histopathological investigation can be retrieved from the duct and the condition can be treated. The patient with nipple discharge is consequently prevented from having to undergo an invasive and fairly 'blindly' executed procedure under general anaesthesia. The miniscule dimensions of the duct in which the technique is carried out pose the greatest challenge to the further development of the ductoscope.

  4. Contemporary pharmacotherapy and iatrogenic pathology

    Directory of Open Access Journals (Sweden)

    Trailović D.R.


    Full Text Available During the past few decades, the pharmaceutical industry has developed into a powerful human activity highly influencing modern medicine. Thousands of synthetic therapeuticals have been developed, and these formulations enabled the successful treatment of many diseases, some of which were considered incurable. An increase in drug consumption followed the development of the pharmaceutical industry and the introduction of synthetic drugs. The widespread use of new medicals enabled the collection of data confirming their effectiveness, but also more and more data concerning side and unwanted effects were reported. Frequent side/unwanted effect reports gave rise to development of iatrogenic pathology, a new branch of clinical pathology. The knowledge of the possible unwanted effects of drugs on macro organisms did not enable the effective withdrawal of such formulations from the market. At the beginning, the reports concerning unwanted effects were not verealed. Consequently some potentially harmful formulations were used for years without methodical analyses of their side/unwanted effects. Some potentially dangerous formulations are still on the market such as drugs containing ulcerogenic, hepatotoxic, nephrotoxic substances as well as those inducing bone marrow aplasia. The administration of these potentially dangerous formulations is understandable in the case of clear therapeutic indications allowing no alternatives. In these cases the risk of harmful side effects is greatly overwhelmed by the risk from the primary disease. Otherwise the administration of the potentially harmful drug is unjustified, especially if the indication is not a disease. Many potentially harmful drugs are formulated for use in healthy animals, recommended as growth, laying and milk stimulators, those allowing higher speed and strength in sport and racing horses, estrus inducers and suppressors. The misuse or maluse medication is highly present in sport horses daily

  5. Erythrocyte membrane proteins and membrane skeleton

    Institute of Scientific and Technical Information of China (English)

    LU Yiqin; LIU Junfan


    Considerable advances in the research field of erythrocyte membrane were achieved in the recent two decades.New findings in the structure-function correlation and interactions of erythrocyte membrane proteins have attracted extensive attention.Interesting progress was also made in the molecular pathogenesis of erythrocyte membrane disorders.Advances in the composition,function and interaction of erythrocyte membrane proteins,erythrocyte membrane skeleton,and relevant diseases are briefly described and summarized here on the basis of domestic and world literatures.

  6. Internal limiting membrane peeling in vitreo-retinal surgery. (United States)

    Abdelkader, Ehab; Lois, Noemi


    Peeling the internal limiting membrane of the retina has become a very common procedure performed by vitreo-retinal surgeons. The combination of new microsurgical instrumentation with the availability of different dyes to stain this thin and transparent membrane has facilitated the performance of internal limiting membrane peeling, reducing the time and trauma associated with this maneuver. Internal limiting membrane peeling has been used to treat a variety of retinal pathologies, including full-thickness macular hole, epiretinal membrane, macular edema, vitreomacular traction syndrome, and Terson syndrome, among others. Although it appears that peeling the internal limiting membrane in these retinal conditions may be associated with better anatomical and visual outcomes following surgery, further evidence through randomized controlled clinical trials is still needed to guide the vitreo-retinal surgeon on the appropriate use of this surgical maneuver.

  7. 3D seismic analysis of gravity-driven and basement influenced normal fault growth in the deepwater Otway Basin, Australia (United States)

    Robson, A. G.; King, R. C.; Holford, S. P.


    We use three-dimensional (3D) seismic reflection data to analyse the structural style and growth of a normal fault array located at the present-day shelf-edge break and into the deepwater province of the Otway Basin, southern Australia. The Otway Basin is a Late Jurassic to Cenozoic, rift-to-passive margin basin. The seismic reflection data images a NW-SE (128-308) striking, normal fault array, located within Upper Cretaceous clastic sediments and which consists of ten fault segments. The fault array contains two hard-linked fault assemblages, separated by only 2 km in the dip direction. The gravity-driven, down-dip fault assemblage is entirely contained within the 3D seismic survey, is located over a basement plateau and displays growth commencing and terminating during the Campanian-Maastrichtian, with up to 1.45 km of accumulated throw (vertical displacement). The up-dip normal fault assemblage penetrates deeper than the base of the seismic survey, but is interpreted to be partially linked along strike at depth to major basement-involved normal faults that can be observed on regional 2D seismic lines. This fault assemblage displays growth initiating in the Turonian-Santonian and has accumulated up to 1.74 km of throw. Our detailed analysis of the 3D seismic data constraints post-Cenomanian fault growth of both fault assemblages into four evolutionary stages: [1] Turonian-Santonian basement reactivation during crustal extension between Australia and Antarctica. This either caused the upward propagation of basement-involved normal faults or the nucleation of a vertically isolated normal fault array in shallow cover sediments directly above the reactivated basement-involved faults; [2] continued Campanian-Maastrichtian crustal extension and sediment loading eventually created gravitational instability on the basement plateau, nucleating a second, vertically isolated normal fault array in the cover sediments; [3] eventual hard-linkage of fault segments in both fault

  8. Pathologic mitoses and pathology of mitosis in tumorigenesis

    Directory of Open Access Journals (Sweden)

    RG Steinbeck


    Full Text Available The gist of my hypothesis (.. is a certain abnormal chromatin constitution. Each process, which brings about this chromatin constitution, would result in the origin of a malignant tumour. Certainly, I consider irregularities with mitosis as the normal mode of the origin of an incorrectly assembled nucleus. This statement by Boveri (1914 has considered earlier observations of asymmetric divisions in human cancers (Hansemann, 1890. The hypothesis is based on the understanding of mitosis as an equational bipartition of the hereditary substance (Flemming, 1879; Roux, 1883. Latest since it was known that genes are located on chromosomes (Sturtevant, 1913, their balanced transport in anaphase appeared as a condition of correct somatic proliferation. True mitoses guarantee the constancy of terminally differentiated tissues. Politzer (1934 has performed X-ray experiments to investigate abnormal karyokinesis with regard to anomalous chromatin condensation, chromosome breakage, spindle malformation, and failure in cytokinesis. On the basis of light microscopy, further significant progress in understanding the pathology of mitosis was not possible. Tumour cases with reduced chromosome numbers seduced to the idea that mitotic activity is rather under cytoplasmic than under nuclear control (Koller, 1947.

  9. On the effectiveness of the vlf-em method For ground water prospecting in the Basement terrains, Sinai, Egypt


    Shendi, El-Arabi Hendi [العربيى هندي شندي


    The VLF-EM method is proved to be an effective, fast and inexpensive tool for ground water prospecting in the basement terrains of Southern Sinai. The resistive shallow alluvial deposits increase the penetration depth of the received VLF waves to as deep as 40 meters which is very reasonable to detect the water bearing alluvium in the studied areas. The measured horizontal and vertical components of the resultant VLF-EM field were used to calculate the apparent resistivities of the conductive...

  10. Integrated Analysis on Gravity and Magnetic Fields of the Hailar Basin, NE China: Implications for Basement Structure and Deep Tectonics (United States)

    Sun, B.; Wang, L.; Dong, P.; Scientific Team Of Applied Geophysics


    The Hailar Basin is one of the most representative basins among the Northeast China Basin Group, which is situated in the east of East Asia Orogene between the Siberia Plate and the North China Plate. Based on the detailed analysis of the Bouguer gravity anomaly, aeromagnetic anomaly as well as petrophysical data, we studied the features of gravity-magnetic fields in the basin and its neighboring areas. A combined approach of Wavelet Multi-scale Decomposition and Power Spectrum Analysis was adopted to quantitatively grade the gravity and magnetic anomalies into four levels. Accordingly, the apparent depths of the source fields can be assessed. The results reveal the crustal density and magnetic structures of the Hailar Basin. Low-order wavelet details of gravity-magnetic anomalies were carried out on studying basin basement structure. Seven major basement faults of the basin were identified, and the basement lithology was discussed and predicted. Three major uplifts and 14 depressions were delineated according to basement depth inversion by the Park method. High-order wavelet approximations of gravity-magnetic anomalies were carried out on studying deep tectonics of the basin. The average Moho depth of the study area is about 40 km, with a mantle uplift located in the northeast of the basin. The average depth of the Curie interface is about 19 km, while the uplift of the Curie interface is in the basin center and its east and west sides are depressions. Finally, inversion of Bouguer gravity anomalies was conducted on an across-basin GGT profile using the Wavelet Multi-scale Decomposition. The inversion results are consistent with those of GGT seismic inversion, suggesting that the Wavelet Multi-scale Decomposition can be applied to distinguish major crustal density interfaces.

  11. Abcc6 deficiency in the mouse leads to calcification of collagen fibers in Bruch's membrane

    NARCIS (Netherlands)

    Gorgels, T.G.; Teeling, P.; Meeldijk, J.D.; Nillesen, S.T.M.; Wal, A.C. van der; Kuppevelt, A.H.M.S.M. van; Bergen, A.A.B.


    Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by mineralization of connective tissue, which leads to pathology in eye, skin and blood vessels. The disease is caused by mutations in ABCC6. To learn more about PXE eye pathology, we analyzed Bruch's membrane (BM) of the eye of an

  12. Metamorphism of the Basement of the Qilian Fold Belt in the Minhe-Ledu Area, Qinghai Province, NW China

    Institute of Scientific and Technical Information of China (English)

    蔡金郎; 魏光华; 王庆树


    The basement of the central Qilian fold belt exposed along the Minhe-Ledu highway consists of psammiticschists, metabasitic rocks, and crystalline limestone. Migmatitic rocks occur sporadically among psammitic schist andmetabasitic rocks. The mineral assemblage of psammitic schist is muscovite + biotite + feldspar + quartz + tourmaline ±titanite ± sillimanite and that of metabasitic rocks is amphibole + plagioclase + biotite ± apatite ± magnetite ± pyroxene ±garnet ± quartz. The migmatitic rock consists of leucosome and restite of various volume proportions; the former consistsof muscovite + alkaline feldspar + quartz ± garnet ± plagioclase while the latter is either fragments of psammitic schist orthose of metabasitic rock. The crystalline limestone consists of calcite that has been partly replaced by olivine. The olivinewas subsequently altered to serpentine. Weak deformations as indicated by cleavages and fractures were imposed promi-nently on the psammitic schists, occasionally on metabasitic rocks, but not on migmatitic rocks. The basement experiencedmetamorphism up to temperature 606-778C and pressure 4.8-6.1 kbar (0.48-0.61 GPa), equivalent to amphibolite-granulite facies. The peak of the metamorphism is marked by a migmatization which occurred at several localities alongthe studied route 587-535 Ma ago. The basement also recorded a retrograde metamorphism of greenschist facies, duringwhich biotite, garnet, amphibole, and pyroxene were partly altered to chlorite.

  13. Ages and Compositions of the Precambrian High-grade Basement of the Qilian Terrane and Its Adjacent Areas

    Institute of Scientific and Technical Information of China (English)


    Based on geological, chronological, geochemical and Nd isotopicstudies of the high-grade basement of the Qilian terrane, the authors have drawn the following main conclusions: (1) the high-grade basement of the Qilian terrane consists mainly of meta-argillo-arenaceous rocks and granites and its bulk part was formed in the period of 0.8-1.0 Ga (the Jinningian period); (2) most of the meta-argillo-arenaceous rocks and granitic rocks have strong negative Eu and Ba anomalies (Eu/Eu*= 0.47-0.71 and Ba/Ba*= 0.16-0.64), with tDM and εNd (1.0 Ga) ranging from 1.87 to 2.26 Ga and from -8.54 to -4.06 respectively, showing relatively high maturity; and (3) the Jinningian granitic rocks are a typical product of continent-continent collision, being probably related to the formation of the supercontinent Rodinia. These studies, com bined with the study of high-grade basement rocks near the Qilian terrane, suggest that before the Jinningian period, the Qilian-Qaidam northern-margin terrane and Dunhuang-Alxa terrane were separated from each other, belonging to differ ent plate systems of the North China craton and Yangtze platform respectively. The Qilian orogenic belt was the same as or similar to the Qiling orogenic belt in terms of the geological evolution history at least before the Jinningian period.

  14. Lateral continuity of basement seismic reflections in 15 Ma ultrafast-spreading crust at ODP Site 1256 (United States)

    Nag, Sreeja; Swift, Stephen A.


    The Ocean Drilling Program (ODP) initiated drilling at Site 1256D in the Guatemala Basin, about 1,000 km off the East Pacific Rise to penetrate plutonic rocks, anticipated to be relatively shallow in this region, formed at an ultra-fast spreading rate. IODP Expedition E312 successfully drilled into gabbros at ~1,150 m in basement. Multi-channel seismic traces show weak laterally coherent sub-basement reflections at borehole depths. Synthetic reflectivity seismograms were computed using a Ricker wavelet and impedance profiles from borehole sonic logs. These seismograms show significant sub-basement amplitude peaks. A zero-offset vertical seismic profile, shot on E312, was processed to investigate the authenticity of these reflections and their relationship to borehole geology. A dual scheme of the median filtering and F-K dip filtering was used. Tests with synthetic seismograms indicate the approach is effective at reasonable SNR levels. Downgoing energy is clearly identified but negligible upgoing energy is visible over random noise. These results indicate that lava flows and igneous contacts in upper ocean crust have significant topography on lateral scales less than the Fresnel Zone (~300 m) due to igneous and tectonic processes.

  15. Spiritual Pathology: The Case of Adolf Hitler

    Directory of Open Access Journals (Sweden)

    W. George Scarlett


    Full Text Available Hitler had a noble purpose (to save the world and a strong faith in the laws of Nature as he understood Nature. He was, then, a spiritual person, though his spirituality was pathological and destructive. Here, the example of Hitler, his faith, and his spiritual pathology is given to both understand spiritual pathology in general and, through contrast, to understand positive spiritual development.

  16. Pathology of the region of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Aufdermaur, M.


    Radiological, clinical and pathologic-anatomical findings seen in four types of disorders of the region of the knee jointare described. An attempt is made to explain the clinical symptomatology on the basis of pathologic-anatomical findings. It is demonstrated that the histology of a giant cell neoplasm does not permit conclusions as to prognosis. Etiology and pathogenesis of villonodular synovitis and of chondrocalcinosis are unexplained. Pathologic-anatomical findings of chondromalacia patellae are those of early osteoarthrosis.

  17. Gray matter pathology and multiple sclerosis. (United States)

    Wegner, Christiane; Stadelmann, Christine


    Gray matter demyelination is frequent and extensive in most patients with multiple sclerosis (MS) and has recently received much attention in neuropathologic and imaging studies. Gray matter lesions show distinct pathologic features that make their detection difficult with conventional imaging techniques. Thus, despite their high prevalence, their impact on clinical symptoms has not been defined well so far. This review focuses on recent information from pathologic and imaging studies and summarizes our current knowledge on cortical pathology derived from human and experimental studies.

  18. Changes in pathological pattern and treatment regimens based on repeat renal biopsy in lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-bao; XU Zheng-jin; LIU Hong-fa; ZHOU Qiu-gen; ZHOU Zhan-mei; JIA Nan


    Background Relapses occur frequently in patients with lupus nephritis.Renal biopsy is the gold standard for assessing renal activity and hence guiding the treatment.Whether repeat renal biopsy is helpful during flares of lupus nephritis remains inconclusive.In the present study,we retrospectively reviewed the patients with lupus nephritis who had more than one renal biopsy with the hope to find the clinical value of repeat biopsy.Methods Patients who had a diagnosis of lupus nephritis and two or more renal biopsies were selected from the database of the patient pathology registration at this renal division.Renal biopsy was evaluated according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis.The pathological patterns and treatment regimens were analyzed after a repeat biopsy.Results We identified 44 systemic lupus erythematosus patients with serial renal biopsies.In total,there were 94 renal biopsies.Overall,the pathological transition occurred in 64% instances according to the ISN/RPS class.When the transition was analyzed according to proliferative,membranous or mix lesions,it showed different profile:35% in patients with proliferative lesion,23.5% patients with mix lesions,100% in patients with pure membranous lesion.The pathological transition could not be predicted by any clinical characteristics.After the repeat renal biopsy,34% of patients had a change in their treatment regimens.Conclusions The pathological conversion was very prevalent in patients with lupus nephritis.However,the transitions became less prevalent when they were analyzed according to pure membranous,proliferative,and mix lesion.Repeat biopsy might be helpful to avoid unnecessary increased immunosuppression therapy.

  19. A study on the seismic AVO signatures of deep fractured geothermal reservoirs in an intrusive basement. (United States)

    Aleardi, M.; Mazzotti, A.


    Amplitude-variation-with-offset (AVO) analysis of reflected waves has become an important tool for hydrocarbon prospecting. However, while the AVO responses of reservoirs in clastic lithologies (oil or gas bearing sands) are well known, the AVO behaviour of reservoirs hosted in the interconnected fractures of massive rocks are almost unknown due to the rarity of this type of reservoirs and the consequent lack of seismic and well log data. Thanks to the availability of the data of boreholes that ENEL GreenPower drilled in the deep intrusive basement of the Larderello-Travale geothermal field, we have derived the expected AVO responses of the vapour reservoirs found in some intensely, but very localized, fractured volumes within the massive rocks. Therefore we wish to determine what are the expected AVO responses of geothermal reservoirs inside fractured igneous rocks and we seek to find one or more AVO attributes that may help identifying fracture locations. To this end, we have analysed the velocity (P-wave and S-wave) and the density logs pertaining to three wells which reached five deep fractured zones in the basement. However, comparing well log data with surface seismic data the known issues of the different scales and thus different resolutions arise. Therefore, making use of the Backus theory of the equivalent layer, we have downscaled the well logs, acquired at a decimetric scale, to a decametric scale typical of the wavelengths of seismic waves, producing a blocky model of the original logs. Subsequently, we have followed two different approaches to estimate the expected responses. First, on the basis of the P and S velocities and densities of the fractured level and of the encasing rock, we have computed the analytical AVO response of each fractured zone. To this end we have made use of the linear Shuey equation that well describes the AVO response up to incident angles of 30 degrees. This would be the theoretical, noise free, response that perfectly

  20. Rift architecture and evolution: The Sirt Basin, Libya: The influence of basement fabrics and oblique tectonics (United States)

    Abdunaser, K. M.; McCaffrey, K. J. W.


    The Cretaceous-Tertiary northwest-trending Sirt Basin system, Libya, is a rift/sag basin formed on Pan-African to Paleozoic-aged basement of North Africa. In this study, we investigate the rift-basin architecture and tectonic framework of the western Sirt Basin. Using remote sensed data, supported by borehole data from about 300 deep wells and surface geologic maps, we constructed geological cross sections and surface geology maps. Indication of the relative timing of structures and movement along faults has been determined where possible. Direction statistics for all the interpreted linear features acquired in the study area were calculated and given as a total distribution and then the totals are broken down by the major basin elements of the area. Hundreds of lineaments were recognized. Their lengths, range between a hundred meters up to hundreds of kilometers and the longest of the dominant trends are between N35W-N55W and between N55E-N65E which coincides with Sirt Basin structures. The produced rose diagrams reveal that the majority of the surface linear features in the region have four preferred orientations: N40-50W in the Zallah Trough, N45-55W in the Dur al Abd Trough, N35-55W in the Az Zahrah-Al Hufrah Platform, and in contrast in the Waddan Uplift a N55-65E trend. We recognize six lithostratigraphic sequences (phases) in the area's stratigraphic framework. A Pre-graben (Pre-rift) initiation stage involved the Pre-Cretaceous sediments formed before the main Sirt Basin subsidence. Then followed a Cretaceous to Eocene graben-fill stage that can divided into four structurally-active and structurally-inactive periods, and finally a terminal continental siliciclastics-rich package representing the post-rift stage of the development in post-Eocene time. In general five major fault systems dissect and divide the study area into geomorphological elevated blocks and depressions. Most of the oil fields present in the study area are associated with structural hinge

  1. The first deep heat flow determination in crystalline basement rocks beneath the Western Canadian Sedimentary Basin (United States)

    Majorowicz, Jacek; Chan, Judith; Crowell, James; Gosnold, Will; Heaman, Larry M.; Kück, Jochem; Nieuwenhuis, Greg; Schmitt, Douglas R.; Unsworth, Martyn; Walsh, Nathaniel; Weides, Simon


    Heat flow (Q) determined from bottom-hole temperatures measured in oil and gas wells in Alberta show a large scatter with values ranging from 40 to 90 mW m-2. Only two precise measurements of heat flow were previously reported in Alberta, and were made more than half a century ago. These were made in wells located near Edmonton, Alberta, and penetrated the upper kilometre of clastic sedimentary rocks yielding heat flows values of 61 and 67 mW m-2 (Garland & Lennox). Here, we report a new precise heat flow determination from a 2363-m deep well drilled into basement granite rocks just west of Fort McMurray, Alberta (the Hunt Well). Temperature logs acquired in 2010-2011 show a significant increase in the thermal gradient in the granite due to palaeoclimatic effects. In the case of the Hunt Well, heat flow at depths >2200 m is beyond the influence of the glacial-interglacial surface temperatures. Thermal conductivity and temperature measurements in the Hunt Well have shown that the heat flow below 2.2 km is 51 mW m-2 (±3 mW m-2), thermal conductivity measured by the divided bar method under bottom of the well in situ like condition is 2.5 W m-1 K-1, and 2.7 W m-1 K-1 in ambient conditions), and the geothermal gradient was measured as 20.4 mK m-1. The palaeoclimatic effect causes an underestimate of heat flow derived from measurements collected at depths shallower than 2200 m, meaning other heat flow estimates calculated from basin measurements have likely been underestimated. Heat production (A) was calculated from spectral gamma recorded in the Hunt Well granites to a depth of 1880 m and give an average A of 3.4 and 2.9 μW m-3 for the whole depth range of granites down to 2263 m, based on both gamma and spectral logs. This high A explains the relatively high heat flow measured within the Precambrian basement intersected by the Hunt Well; the Taltson Magmatic Zone. Heat flow and related heat generation from the Hunt Well fits the heat flow-heat generation

  2. [Arachnoid cysts: Embriology and pathology]. (United States)

    García-Conde, Mario; Martín-Viota, Lucia


    There is still great controversy surrounding the origin of the arachnoid cyst. The most accepted theory in the case of congenital cysts explains how they are formed from an anomalous development of the arachnoid membrane, which is unfolded allowing the accumulation of cerebrospinal fluid inside and creating a cyst. This theory seems to explain the origin of convexity and sylvian cistern arachnoid cysts, whereas those in other locations might be due to other mechanisms. In the anatomopathological analysis, the arachnoid cyst wall can be seen as having few differences from normal, although thickened due to an increase quantity of collagenous material. A description of the embryological development of the arachnoid layer and cyst formation is presented, describing the main anatomopathological findings.

  3. Distinguishing Grenvillian basement from pre-Taconian cover rocks in the Northern Appalachians (United States)

    Karabinos, P.; Aleinikoff, J.N.; Fanning, C.M.


    Distinguishing Grenvillian basement rocks from pre-Taconian cover sequences in the Appalachians is a first-order problem essential for accurate structural interpretations. The Cavendish Formation in southeastern Vermont presents a classic example of this problem. Doll and others (1961) showed the Cavendish Formation as younger than the Middle Proterozoic Mount Holly Complex but older than the lithologically similar Cambrian Tyson and Hoosac Formations. More recently, the name Cavendish Formation has been informally abandoned, and its metasedimentary units have been mapped as the Tyson and Hoosac Formations of Late Proterozoic to Cambrian age. In a radical departure from these interpretations, Ratcliffe and others (1997) reassigned metasedimentary rocks of the Cavendish Formation to the Mount Holly Complex based on an inferred intrusive relationship between them and a 1.42 Ga tonalite. This new age assignment, if correct, requires a completely new structural interpretation of the region. SHRIMP and Pb evaporation ages of detrital zircons extracted from a quartzite layer from Cavendish Gorge near the proposed intrusive contact with the tonalite constrain the time of deposition of the Cavendish Formation. Grain shapes of the zircons vary from euhedral to nearly spherical. Virtually all the grains have pitted surfaces and show at least some rounding of edges and terminations; grains exhibit oscillatory zoning typical of zircons that crystallized from a magma. Single-grain Pb evaporation analyses of ten zircons and SHRIMP analyses of 15 zircons all yield ages less than 1.42 Ga. Seven of the grains are consistent with derivation from the Bull Hill Gneiss that postdates the Grenville orogenic cycle and predates deposition of the Cavendish Formation. Thus, the metasedimentary units of the Cavendish Formation should not be assigned to the Mount Holly Complex.

  4. Compositional asynchronous membrane systems

    Institute of Scientific and Technical Information of China (English)

    Cosmin Bonchis; Cornel Izbasa; Gabriel Ciobanu


    This paper presents an algorithmic way of building complex membrane systems by coupling elementary membranes. Its application seems particularly valuable in the case of asynchronous membrane systems, since the resulting membrane system remains asynchronous. The composition method is based on a handshake mechanism implemented by using antiport rules and promoters.

  5. Composite sensor membrane (United States)

    Majumdar, Arun; Satyanarayana, Srinath; Yue, Min


    A sensor may include a membrane to deflect in response to a change in surface stress, where a layer on the membrane is to couple one or more probe molecules with the membrane. The membrane may deflect when a target molecule reacts with one or more probe molecules.

  6. Magnetically controlled permeability membranes

    KAUST Repository

    Kosel, Jurgen


    A bioactive material delivery system can include a thermoresponsive polymer membrane and nanowires distributed within the thermoresponsive polymer membrane. Magnetic activation of a thermoresponsive polymer membrane can take place via altering the magnetization or dimensions of nanowires dispersed or ordered within the membrane matrix.

  7. Two-dimensional basement modeling of central loop transient electromagnetic data from the central Azraq basin area, Jordan (United States)

    Yogeshwar, P.; Tezkan, B.


    Thick sedimentary sequences are deposited in the central area of the Azraq basin in Jordan consisting mostly of hyper-saline clay and various evaporates. These sediment successions form the 10 km × 10 km large Azraq mudflat and are promising archives for a palaeoclimatical reconstruction. Besides palaeoclimatical research, the Azraq area is of tremendous importance to Jordan due to groundwater and mineral resources. The heavy exploitation of groundwater has lead to a drastic decline of the water table and drying out of the former Azraq Oasis. Two 7 and 5 km long transects were investigated from the periphery of the mudflat across its center using a total of 150 central loop transient electromagnetic (TEM) soundings. The scope of the survey was to detect the thickness of sedimentary deposits along both transects and to provide a basis for future drilling activities. We derive a two-dimensional model which can explain the TEM data for all soundings along each profile simultaneously. Previously uncertain depths of geological boundaries were determined along both transects. Particularly the thickness of the deposited mudflat sediments was identified and ranges from 40 m towards the periphery down to approximately 130 m at the deepest location. Besides that, the depth and lateral extent of a buried basalt layer was identified. In the basin center the groundwater is hyper-saline. The lateral extent of the saline water body was determined precisely along both transects. In order to investigate the detectability of the basement below the high conductive mudflat sediments an elaborate two-dimensional modeling study was performed. Both, the resistivity and depth of the basement were varied systematically. The basement resistivity cannot be determined precisely in most zones and may range roughly between 1 and 100 Ωm without deteriorating the misfit. In contrast to that, the depth down to the basement is detected accurately in most zones and along both transects. Varying

  8. Digital data for depth to basement in the deep-sea basins of the Pacific continental margin (cowbsm) based on data collected in 1984. (United States)

    U.S. Geological Survey, Department of the Interior — Digital vector data for the contours of depth to basement for the deep-sea basins of the Pacific continental margin offshore of Washington, Oregon, and California....

  9. Two-stage formation model of the Junggar basin basement: Constraints to the growth style of Central Asian Orogenic Belt (United States)

    He, Dengfa


    Junggar Basin is located in the central part of the Central Asian Orogenic Belt (CAOB). Its basement nature is a highly controversial scientific topic, involving the basic style and processes of crustal growth. Some researchers considered the basement of the Junggar Basin as a Precambrian continental crust, which is not consistent with the petrological compositions of the adjacent orogenic belts and the crust isotopic compositions revealed by the volcanic rocks in the basin. Others, on the contrary, proposed an oceanic crust basement model that does not match with the crustal thickness and geophysical characteristics of the Junggar area. Additionally, there are several viewponits, such as the duplex basement with the underlying Precambrian crystalline rocks and the overlying pre-Carboniferous folded basement, and the collaged basement by the Precambrian micro-continent block in the central part and the Hercynian accretionary folded belts circling it. Anyway, it is necessary to explain the property of basement rock, its strong inhomogeneous compositions as well as the geophysical features. In this paper, based on the borehole data from more than 300 industry wells drilled into the Carboniferous System, together with the high-resolution gravity and magnetic data (in a scale of 1:50,000), we made a detailed analysis of the basement structure, formation timing and processes and its later evolution on a basis of core geochemical and isotopic analysis. Firstly, we defined the Mahu Pre-Cambrian micro-continental block in the juvenile crust of Junggar Basin according to the Hf isotopic analysis of the Carboniferous volcanic rocks. Secondly, the results of the tectonic setting and basin analysis suggest that the Junggar area incorporates three approximately E-W trending island arc belts (from north to south: Yemaquan- Wulungu-Chingiz, Jiangjunmiao-Luliang-Darbut and Zhongguai-Mosuowan- Baijiahai-Qitai island arcs respectively) and intervened three approximately E-W trending

  10. Enhancement of Seismic Data Processing and Interpretation of Fracture Zones on the Upper Part of Granitic Basement in Cuu Long Basin, Vietnam

    Directory of Open Access Journals (Sweden)

    Tan Mai Thanh


    Full Text Available The fractured granite basement is the primary oil and gas reservoir in the Cuu Long Basin, Vietnam. Due to the complexity of this non-layered unconventional target, combined with complicated fault and fracture systems, the seismic data quality near and within the basement section is very low. For this reason, it is important to apply improved seismic data processing workflows, filtering and migration techniques, as wells as attribute processing methods to enhance the imaging quality.

  11. Pathological Gambling and Related Problems among Adolescents. (United States)

    Ladouceur, Robert; Boudreault, Normand; Jacques, Christian; Vitaro, Frank


    Evaluates the prevalence of pathological gambling and related problems among 3,426 students in junior and senior high schools in Quebec City. Results indicate that 77% have gambled in the last twelve months and 13% gamble at least once a week. Results also reveal that pathological gambling is associated with drug and alcohol use, poor grades, and…

  12. Trends in pathology graduate medical education. (United States)

    Alexander, C B


    Comprehensive data show trends in graduate medical education in pathology with regard to the numbers of accredited programs, persons certified from those programs, and demographics of the population of first year-trainees in pathology. Experience with US seniors and foreign-trained physicians in the PGY match process for pathology from 1991 through 2000 is presented, along with data on the types of medical schools generating pathology trainees for the PGY-1 year and the top medical schools of origin of US medical graduates who completed the program and became certified in pathology between 1995 and 1999. The impact of reimbursement of the credentialing year is also addressed through data collected from the PRODS Survey 2000, and those results are reviewed. Finally, turnover rates among pathology program directors of combined AP/CP programs and subspecialty programs since 1994 are presented. An analysis of these trends is provided, along with suggestions to improve both the perception of careers in pathology and the actual choice of a career in pathology.

  13. Shifted risk preferences in pathological gambling

    NARCIS (Netherlands)

    Ligneul, R.; Sescousse, G.T.; Barbalat, G.; Domenech, P.; Dreher, J.C.


    BACKGROUND: Pathological gambling (PG) is an impulse control disorder characterized by excessive monetary risk seeking in the face of negative consequences. We used tools from the field of behavioral economics to refine our description of risk-taking behavior in pathological gamblers. This theoretic

  14. Pathology of the parathyroid glands in hyperparathyroidism. (United States)

    Baloch, Zubair W; LiVolsi, Virginia A


    This paper reviews the embryology, histology and pathology of the human parathyroid glands. It emphasizes those pathologic lesions which are found in the setting of clinical hyperparathyroidism. Also discussed are certain molecular features of hyperfunctioning parathyroid glands. The difficulties encountered in parathyroid FNA are reviewed and illustrated.

  15. Membranous lipodystrophy: skeletal findings on CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Nwawka, O.K.; Schneider, Robert; Mintz, Douglas N. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Bansal, Manjula [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States); Lane, Joseph [Hospital for Special Surgery, Department of Orthopedic Surgery, New York, NY (United States)


    Membranous lipodystrophy, also known as Nasu-Hakola disease, is a rare hereditary condition with manifestations in the nervous and skeletal systems. The radiographic appearance of skeletal lesions has been well described in the literature. However, CT and MRI findings of lesions in the bone have not been documented to date. This report describes the radiographic, CT, MRI, and histopathologic skeletal findings in a case of membranous lipodystrophy. With corroborative pathologic findings, a diagnosis of membranous lipodystrophy on imaging allows for appropriate clinical management of disease manifestations. (orig.)

  16. Membranous lipodystrophy: skeletal findings on CT and MRI. (United States)

    Nwawka, O Kenechi; Schneider, Robert; Bansal, Manjula; Mintz, Douglas N; Lane, Joseph


    Membranous lipodystrophy, also known as Nasu-Hakola disease, is a rare hereditary condition with manifestations in the nervous and skeletal systems. The radiographic appearance of skeletal lesions has been well described in the literature. However, CT and MRI findings of lesions in the bone have not been documented to date. This report describes the radiographic, CT, MRI, and histopathologic skeletal findings in a case of membranous lipodystrophy. With corroborative pathologic findings, a diagnosis of membranous lipodystrophy on imaging allows for appropriate clinical management of disease manifestations.

  17. Sheet Membrane Spacesuit Water Membrane Evaporator (United States)

    Bue, Grant; Trevino, Luis; Zapata, Felipe; Dillion, Paul; Castillo, Juan; Vonau, Walter; Wilkes, Robert; Vogel, Matthew; Frodge, Curtis


    A document describes a sheet membrane spacesuit water membrane evaporator (SWME), which allows for the use of one common water tank that can supply cooling water to the astronaut and to the evaporator. Test data showed that heat rejection performance dropped only 6 percent after being subjected to highly contaminated water. It also exhibited robustness with respect to freezing and Martian atmospheric simulation testing. Water was allowed to freeze in the water channels during testing that simulated a water loop failure and vapor backpressure valve failure. Upon closing the backpressure valve and energizing the pump, the ice eventually thawed and water began to flow with no apparent damage to the sheet membrane. The membrane evaporator also serves to de-gas the water loop from entrained gases, thereby eliminating the need for special degassing equipment such as is needed by the current spacesuit system. As water flows through the three annular water channels, water evaporates with the vapor flowing across the hydrophobic, porous sheet membrane to the vacuum side of the membrane. The rate at which water evaporates, and therefore, the rate at which the flowing water is cooled, is a function of the difference between the water saturation pressure on the water side of the membrane, and the pressure on the vacuum side of the membrane. The primary theory is that the hydrophobic sheet membrane retains water, but permits vapor pass-through when the vapor side pressure is less than the water saturation pressure. This results in evaporative cooling of the remaining water.

  18. Pathological characteristics of gastric leiomyoblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Huang; Chun-Mei Wang; Bo-Rong Pan; Xiao-Wen Dai; Li Fang; Jia-Ji Yang; Hua Yu; Jun Ren


    AIM: To determine the pathological characteristics of gastric leiomyoblastoma.METHODS: All tissues were obtained during surgery or gastroscopy. Tissue specimens for examination by light microscope were 1 cm×1 cm×1 cm in size, fixed in 40 g/L neutral buffered formaldehyde, embedded in paraffin, and stained with hematoxylin and eosin. The fresh tissues obtained for electron microscopy were 1 mm×1 mm×1 mm in size,and fixed in phosphate buffered 30 g/L glutaraldehyde,postfixed in 10 g/L osmium tetroxide and dehydrated in graded alcohol, embebbed in Epon 812. Ultrathin sections of 50 nm were stained with uranyl acetate and lead citrate and examined under a JEM-2000 EX transmission electron microscope.RESULTS: The most important histopathological feature of leiomyoblastoma was the predominance of large, rounded or polygonal cells with characteristic perinuclear clear zone in cytoplasms. The tumor cells arranged in patch, cell junction or junctional complex could be found occasionally between cells under electron microscope. Most of the neoplastic cytoplasms were filled with myofilaments, dense bodies, and dense patches. Rough endoplasmic reticulum dilatated as lakes, and large quantities of protein secretions of intermediate electron density were found in the dilated cisternae. Intracisternal segregation could also be found.The nuclei were round or oval, and anomalous nuclei were found in part of cells.CONCLUSION: The diagnosis of gastric leiomyoblastoma can be confirmed by electron microscopy. The clear appearance of tumor cells is due to the dilation of rough endoplasmic reticulum, not fat droplets, glycogens or mucus in cytoplasm.

  19. A Pathogenic Potential of Acinetobacter baumannii-Derived Membrane Vesicles

    Directory of Open Access Journals (Sweden)

    Jong Suk Jin


    Full Text Available Acinetobacter baumannii secretes outer membrane vesicles (OMVs. A. baumannii OMVs deliver many virulence factors to host cells and then induce cytotoxicity and innate immune response. OMVs secreted from bacteria contribute directly to host pathology during A. baumannii infection.

  20. Decrypting the Formation Conditions of the Basement Carbonate-Bearing Rocks at Nili Fossae (United States)

    Brown, A. J.


    The Nili Fossae region is the site of a number of proposed Landing Sites for the Mars 2020 Rover. A distinguishing feature of many of these sites is the access to large exposures of carbonate (Ehlmann et al. 2008). Serpentinization has been proposed as a formation mechanism of these carbonates, including carbonated (Brown et al. 2010, Viviano, et al. 2013) and low temperature, near surface serpentinization. The potential for carbonated serpentization at Nili Fossae links the region to Earth analogs in terrestrial greenstone belts such as the Pilbara in Western Australia, where talc-carbonate bearing komatiite cumulate units of the Dresser Formation overlie the siliceous, stromatolite-bearing Strelley Pool Chert unit (Van Kranendonk and Pirajno, 2004). If a similar relationship exists on Mars, investigations of rocks stratigraphically beneath the carbonate-bearing units at Nili Fossae ("the basement rocks") may provide the best chance to examine well preserved organic material from the Noachian. This hypothesis is testable by Mars 2020. In preparation for the the Mars 2020 landing site, we are examining the thermodynamic relationships that favor formation of serpentine and talc-carbonate and different pressures and temperatures in the crust (Barnes 2007). This will allow us to constrain the low grade metamorphism required to replicate the proposed models of serpentinisation and help us understand the regional metamophic gradient that is critical to furthering our knowledge of the ancient rocks of Nili Fossae. Refs:Barnes, S. J. "Komatiites: Petrology, Volcanology, Metamorphism, and Geochemistry." S.E.G. 13 (2007): 13. Brown, A. J., et al.. "Hydrothermal Formation of Clay-Carbonate Alteration Assemblages in the Nili Fossae Region of Mars." EPSL 297 (2010): 174-82. Ehlmann, B. L. et al. "Orbital Identification of Carbonate-Bearing Rocks on Mars." Science 322, no. 5909 1828-32. Van Kranendonk, M.J., and F. Pirajno. "Geochemistry of Metabasalts and Hydrothermal