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Sample records for basement membrane disease

  1. AUTOIMMUNE BASEMENT MEMBRANE AND SUBEPIDERMAL BLISTERING DISEASES

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    Ana Maria Abreu Velez

    2013-11-01

    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

  2. Anti-glomerular basement membrane blood test

    Science.gov (United States)

    ... used to diagnose certain kidney diseases, such as Goodpasture syndrome and anti-glomerular basement membrane disease. ... the blood may mean any of the following: Anti-glomerular basement membrane disease Goodpasture syndrome

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

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    Nivera Noel

    2010-08-01

    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.

  4. 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;

    1994-01-01

    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...

  5. 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

    1994-01-01

    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 di...

  6. Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular Basement Membrane Disease.

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    Li, Jian-Nan; Cui, Zhao; Wang, Jia; Hu, Shui-Yi; Jia, Xiao-Yu; Guan, Zhe; Chen, Min; Xie, Can; Zhao, Ming-Hui

    2016-04-07

    Approximately 20%-30% of patients with anti-glomerular basement membrane disease present coexisting anti-myeloperoxidase (MPO) autoantibodies. We previously showed the recognition of a linear fragment of the MPO heavy chain N-terminus ((1)H, MPO279-409) in plasma from most double-positive patients. Herein, we investigated the frequency of autoantibodies against overlapping (1)H-derived linear peptides in plasma from patients with anti-glomerular basement membrane disease. We synthesized 13 overlapping linear peptides ((1)H-1 to (1)H-13) covering MPO279-409. We retrospectively collected plasma samples from 67 patients with anti-glomerular basement membrane disease from 1996 to 2012, and we screened them for IgG autoantibodies by ELISA using intact human MPO and the overlapping peptides as antigens, and we further investigated the clinical significance. Autoantibody binding to the linear MPO structure was confirmed by Western blotting. We followed up the 67 patients until 2015, with a median follow-up time of 10.0 (2.3-36.0) months, and 56 ESRD events occurred among the 67 patients with follow-up data. Plasma from 23.9% (16) of the patients recognized intact human MPO, whereas 62.7% (42) plasma samples recognized MPO279-409 linear peptides. Of the 13 linear peptides, (1)H-4 (44.8%, 30 patients) and (1)H-12 (40.3%, 27 patients) exhibited the highest recognition frequencies. Patients with autoantibodies against (1)H-11 or (1)H-12 (MPO371-400) were older (46.1±18.8 versus 34.1±16.6 years; P<0.01), had higher serum creatinine upon diagnosis (median 7.8 mg/dl, interquartile range 4.9-12.6 mg/dl versus median 5.4 mg/dl, interquartile range 2.4-7.3 mg/dl; P=0.02), and had a higher probability of progressing to ESRD; however, multivariate Cox regression analysis showed that (1)H-11 or 12 reaction was not an independent risk factor for renal failure (hazard ratio, 1.2; 95% confidence interval, 0.8 to 2.8; P=0.19). Autoantibodies against linear peptides of MPO can be

  7. An unusual case of anti-glomerular basement membrane disease presenting with nephrotic syndrome.

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

    2011-12-01

    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.

  8. The nature and biology of basement membranes.

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

    2017-01-01

    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.

  9. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.

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

    2015-01-01

    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.

  10. 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.;

    1999-01-01

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

  11. Validation of glomerular basement membrane thickness changes with aging in minimal change disease.

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

    2010-01-01

    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.

  12. IgA-mediated anti-glomerular basement membrane disease: an uncommon mechanism of Goodpasture's syndrome.

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    Moulis, Guillaume; Huart, Antoine; Guitard, Joëlle; Fortenfant, Françoise; Chauveau, Dominique

    2012-12-01

    Goodpasture's (GP) disease is usually mediated by IgG autoantibodies. We describe a case of IgA-mediated GP, in a patient presenting with isolated rapidly progressive glomerulonephritis. The diagnosis was established on kidney biopsy, since routine enzyme-linked immunosorbent assay (ELISA) targeted at IgG circulating autoantibodies failed to detect the nephritogenic antibodies. Immunofluorescence microscopy showed intense linear deposition of IgA along the glomerular capillary walls. An elevated titre (1:80) of circulating IgA anti-glomerular basement membrane (GBM) antibodies was retrospectively demonstrated by indirect fluorescence. Despite immunosuppressive regimen, the disease progressed to end-stage renal failure (ESRF). Transplantation was not associated with recurrence in the kidney graft. We reviewed the 11 previously reported cases of IgA-mediated GP.

  13. Basement membrane proteoglycans and development

    DEFF Research Database (Denmark)

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

    1993-01-01

    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...

  14. Anti-glomerular basement membrane antibodies.

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    Silvariño, Ricardo; Noboa, Oscar; Cervera, Ricard

    2014-11-01

    Basement membranes form an anatomic barrier that contains connective tissue. They are composed of type IV collagen, laminin and proteoglycans. Anti-basement membrane antibodies bind to the non-collagen site of the α3 chain of type IV collagen. A group of renal diseases, pulmonary diseases and perhaps others affecting different organs have long been associated with the presence of antibodies directed against glomerular basement membrane (GBM), alveolar basement membrane and tubular basement membrane. Goodpasture disease has a frequency of 0.5 to 1 case by million/year, and is responsible for up to 20% of crescentic glomerulonephritis in renal biopsy. It has been associated with genetic and immune abnormalities and there are usually environmental triggers preceding clinical onset. Renal disease can occur isolated or in association with pulmonary hemorrhage. In general, renal disease has a rapid progression that determines severe compromise, with rare spontaneous resolution. The diagnosis of Goodpasture disease requires the presence of the anti-GBM antibody, either in circulation or in renal tissue. The prognosis of non-treated patients is poor. The standard of care is plasma exchange combined with prednisone and cyclophosphamide. Anti-GBM antibody levels must be monitored frequently until their disappearance, and then every 6 months to confirm sustained remission in the absence of clinical signs of recurrence. Prognosis of the disease is strongly associated with its initial presentation. Survival rates are related to the degree of renal compromise at onset of the disease. Recurrence of the disease post-transplantation is low.

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

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    Cristen Chafin

    2010-10-01

    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. Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement membrane disease.

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    Wang, Aifeng; Wang, Yongping; Wang, Guobao; Zhou, Zhanmei; Xun, Zhang; Tan, Xiaohui

    2012-05-01

    Anti-glomerular basement membrane (anti-GBM) disease is characterized by crescentic glomerulonephritis with immunoglobulin G (IgG) autoantibodies to the non-collagenous (NC1) domain of α3(IV) collagen presenting along the GBM. The patient clinically manifests with rapidly progressive glomerulonephritis (RPGN) with pulmonary hemorrhage (Goodpasture syndrome). In rare cases, other immunocomplexes of IgA or IgM are involved, but their specificities have not been determined. We report a rare case of a 31-year-old female who was diagnosed as having anti-GBM disease with extensive IgA deposits in the mesangium. This patient presented heavy hematuria, proteinuria with increasing creatinine, but no lung hemorrhage. Renal biopsy showed crescentic glomerulonephritis (type Ⅰ) with strong IgA (3+) as lump and branch shape. Therapies with pulse methylprednisolone, plasmapheresis and cyclophosphamide administration were less effective. This case is different from the present type Ⅰ crescentic glomerulonephritis and the specificity of IgA deposits may implicate the pathogenesis of anti-GBM disease.

  17. Goodpasture syndrome involving overlap with Wegener's granulomatosis and anti-glomerular basement membrane disease.

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    Kalluri, R; Meyers, K; Mogyorosi, A; Madaio, M P; Neilson, E G

    1997-11-01

    A 68-year-old Caucasian woman presented to the hospital with nodular pulmonary infiltrates and acute renal failure. Wegener's granulomatosis was initially considered to be most likely because of the presence of increased serum levels of c-anti-neutrophil cytoplasmic antibodies (c-ANCA). A consultation through the Internet after a renal biopsy demonstrated crescentic, necrotizing glomerulonephritis and linear deposits of immunoglobulin G (IgG) and complement C3, typical of anti-glomerular basement membrane (GBM) disease. Hemodialysis was instituted; however, the patient suddenly developed a massive cerebral hemorrhage and died before full therapy could take effect. Postmortem analysis of the patient's sera revealed high titers of IgG against the alpha 3 NC1 domain of type IV collagen. Serologic evidence of both p-ANCA and anti-GBM antibodies are becoming more frequently recognized in the setting of rapidly progressive glomerulonephritis. The patient reported here had the unusual combination of c-ANCA antibodies with anti-GBM disease, and this association raises complex questions regarding the pathogenesis of this type of renal injury.

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

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    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.

  19. A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study

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    Umesh Lingaraj

    2017-01-01

    Full Text Available Acute glomerulonephritis due to anti-glomerular basement membrane (anti-GBM antibody disease is rare, estimated to occur in fewer than one case per million population and accounts for less than 20% of rapidly progressive glomerulonephritis. The prevalence among patients evaluated for potential glomerular disease is lower. It accounts for fewer than 3% of all kidney biopsies done with crescentic glomerulonephritis. Cases of anti-GBM disease occurring in a cluster have rarely been reported. All biopsy proven anti-GBM disease cases were collected from January 2015 to March 2015 at our Institute. All cases were analyzed for demographic and clinical profile, pathological findings, treatment received and for any common environmental antigenic source. A total of 11 new biopsy proven anti-GBM cases were seen within a span of three months. Age group varied from 17–80 years. Seven were males and four were females. All were dialysis dependent at presentation. Seven had active cellular crescents, and four had fibrocellular. Only one patient was a smoker and none had a history of exposure to any forms of hydrocarbons. The peak seen from January 2015 to March 2015 does not correlate with any of seasonal occurrence of infections in southern India. Although there was clustering of cases to southern territories of Karnataka state, no common etiological agents could be identified. No patient had any previous urological surgeries. All patients received methylprednisolone with plasmapheresis 5–7 sessions and cyclophosphamide. All 11 patients were dialysis dependent at the end of three months. We conclude anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. The occurrence of such epidemic within a short period suggests a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of such inciting agents could help us in instituting appropriate preventing measures.

  20. Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit.

    OpenAIRE

    Coimbra, T.; Wiggins, R.; Noh, J. W.; Merritt, S.; Phan, S. H.

    1991-01-01

    The purpose of this study was to assay for the presence of collagen synthesis stimulatory activity in the kidney during immune-induced renal injury that results in severe fibrosis in both glomerular and interstitial compartments. A model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on day 0 by the injection of anti-GBM antibody and renal cortex tissues were then sampled at various time points. Only conditioned media prepared from diseased renal cortical samples show...

  1. Laminins in basement membrane assembly.

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    Hohenester, Erhard; Yurchenco, Peter D

    2013-01-01

    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.

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

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    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.

  3. Case report of anti-glomerular basement membrane disease following alemtuzumab treatment of relapsing-remitting multiple sclerosis.

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    Meyer, David; Coles, Alasdair; Oyuela, Pedro; Purvis, Annie; Margolin, David H

    2013-01-01

    To report a case of anti-glomerular basement membrane disease (anti-GBM disease) during alemtuzumab treatment of a relapsing-remitting multiple sclerosis (RRMS) patient. Case report. Outpatient neurology research protocol. A 35-year-old white female receiving alemtuzumab for RRMS in a clinical research protocol developed symptoms leading to diagnosis of anti-GBM disease. Patient response to the treatment of anti-GBM disease and RRMS. Early identification and treatment of anti-GBM disease resolved clinical symptoms and preserved renal function. Alemtuzumab treatment of RRMS resolved initial MS symptoms and appears to have controlled active disease to date. Close monitoring for potential side effects of alemtuzumab treatment in RRMS resulted in a positive outcome when anti-GBM disease was recognized and treated early. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. A model of strain-dependent glomerular basement membrane maintenance and its potential ramifications in health and disease.

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

    2012-08-01

    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.

  5. [Clinical consequence and significance of anti-neutrophil cytoplasmic antibody positivity in anti-glomerular basement membrane disease].

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    File, Ibolya; Pucsok, Klára; Trinn, Csilla; Ujhelyi, László; Balla, József; Mátyus, János

    2013-10-27

    Patients with renopulmonary syndrome who have both anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies have been described since 1989. The aim of the authors was to analyse the data of "double positive" patients diagnosed in their department, and compare these with previous studies. During the last 16 years, 87 anti-neutrophil cytoplasmic antibody positive and 11 anti-glomerular basement membrane antibody positive patients were diagnosed. Four patients with anti-glomerular basement membrane antibodies (36%) had detectable anti-neutrophil cytoplasmic antibodies, 2 patients were positive for anti-myeloperoxidase and 2 patients for anti-proteinase 3. In comparison with patients having anti-glomerular basement membrane antibodies, the double-positive patients were characterized by older age (median of 46 vs. 24 years), lack of male dominance (50% vs. 71%), more frequent presence of previous extrarenal symptoms (50% vs. 0%), and lower anti-glomerular basement membrane antibody levels (<100EU/ml: 100% vs. 29%). The double-positive patients had more favourable 1-year survival (100% vs. 71%), despite their older age and similar treatment regimen (immunosuppression 100% in both groups, plasmapheresis in 75% vs. 86%), but 1-year renal survival was not different (25% vs. 14%). In agreement with literature data, about one third of patients with anti-glomerular basement membrane antibodies had detectable anti-neutrophil cytoplasmic antibodies, and the coexistence of the two antibodies may have clinical consequences.

  6. Anti-glomerular basement membrane disease: Case series from a tertiary center in North India.

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    Prabhakar, D; Rathi, M; Nada, R; Minz, R W; Kumar, V; Kohli, H S; Jha, V; Gupta, K L

    2017-01-01

    Anti-glomerular basement (anti-GBM) disease is an uncommon disorder with a bimodal age of presentation. Patients presenting with dialysis-dependent renal failure have poor renal outcomes. There is limited data regarding the clinical presentation and outcomes of anti-GBM disease from India. We conducted this prospective study to analyze the clinical presentation and outcomes of anti-GBM disease at a large tertiary care hospital in North India over 1½ years. Subjects with a biopsy proven anti-GBM disease (light microscopic examination showing crescents and immunofluorescence examination showing linear deposition of IgG) with or without positive anti-GBM antibodies in serum were included in the study and followed-up for at least 12 months. All the patients were treated with steroids, cyclophosphamide, and plasma exchange. A total of 17 patients (nine males) were included. The mean age at presentation was 39.11 ± 16.58 (range 11-72) years. Twelve patients (70%) presented with rapidly progressive glomerulonephritis (RPGN), 4 (23.5%) presented with Goodpasture syndrome, while 1 (5.8%) had nephritic syndrome, 7 (41%) were hypertensive, and 14 (82.3%) required dialysis at the time of presentation. Four patients (23.5%) had associated anti-neutrophil cytoplasmic antibody positivity (anti-myeloperoxidase antibodies in all). Fourteen (87.5%) patients had crescentic glomerulonephritis, while 5 (31.25%) showed necrotizing (n = 4) or granulomatous (n = 1) in the vasculitis. Of 16 patients who received treatment, four (23.25%) achieved complete remission. In this single-center study, the majority of anti-GBM disease patients presented with RPGN and had crescentic glomerulonephritis on biopsy with poor treatment outcome.

  7. Anti-glomerular basement membrane disease: Case series from a tertiary center in North India

    Directory of Open Access Journals (Sweden)

    D Prabhakar

    2017-01-01

    Full Text Available Anti-glomerular basement (anti-GBM disease is an uncommon disorder with a bimodal age of presentation. Patients presenting with dialysis-dependent renal failure have poor renal outcomes. There is limited data regarding the clinical presentation and outcomes of anti-GBM disease from India. We conducted this prospective study to analyze the clinical presentation and outcomes of anti-GBM disease at a large tertiary care hospital in North India over 1½ years. Subjects with a biopsy proven anti-GBM disease (light microscopic examination showing crescents and immunofluorescence examination showing linear deposition of IgG with or without positive anti-GBM antibodies in serum were included in the study and followed-up for at least 12 months. All the patients were treated with steroids, cyclophosphamide, and plasma exchange. A total of 17 patients (nine males were included. The mean age at presentation was 39.11 ± 16.58 (range 11–72 years. Twelve patients (70% presented with rapidly progressive glomerulonephritis (RPGN, 4 (23.5% presented with Goodpasture syndrome, while 1 (5.8% had nephritic syndrome, 7 (41% were hypertensive, and 14 (82.3% required dialysis at the time of presentation. Four patients (23.5% had associated anti-neutrophil cytoplasmic antibody positivity (anti-myeloperoxidase antibodies in all. Fourteen (87.5% patients had crescentic glomerulonephritis, while 5 (31.25% showed necrotizing (n = 4 or granulomatous (n = 1 in the vasculitis. Of 16 patients who received treatment, four (23.25% achieved complete remission. In this single-center study, the majority of anti-GBM disease patients presented with RPGN and had crescentic glomerulonephritis on biopsy with poor treatment outcome.

  8. [Ultrastructure of glomerular podocyts in the incipient phase of minimal change nephrotic syndrome with thin basement membrane disease].

    Science.gov (United States)

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

    2012-01-01

    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.

  9. Monoclonal IgG1κ anti-glomerular basement membrane disease: a case report.

    Science.gov (United States)

    Coley, Shana M; Shirazian, Shayan; Radhakrishnan, Jai; D'Agati, Vivette D

    2015-02-01

    We report a case of anti-glomerular basement membrane (anti-GBM) nephritis with indolent course, monoclonal IgG1κ (immunoglobulin G, subclass 1, κ light chain) linear staining of the GBM, and multifocal GBM breaks but without crescents or detectable serum anti-GBM antibody in a patient followed over 9 years. Atypically, anti-GBM nephritis follows an indolent course. A very small fraction of patients with anti-GBM nephritis lack detectable circulating anti-GBM antibodies, and rare reports of monoclonal anti-GBM nephritis exist. We report what is to our knowledge the first case manifesting all 3 of these rare variations. Our patient initially presented with asymptomatic decreased kidney function following an upper respiratory tract infection. He was found to have microhematuria and subnephrotic proteinuria with mild diffuse endocapillary proliferative and exudative glomerulonephritis with linear IgG1κ staining of the GBM. He was treated with an induction regimen of intravenous cyclophosphamide and corticosteroids followed by maintenance monotherapy with mycophenolic acid. Nine years later, repeat kidney biopsy for worsening kidney function after an upper respiratory tract infection showed persistent monoclonal staining of the GBM and acute glomerulonephritis with increased chronicity, including a single fibrocellular crescent. Despite extensive clinical investigations spanning nearly a decade, no circulating anti-GBM antibody or monoclonal protein has been detected. In this case report, we explore the unique features of this monoclonal IgG1κ-associated anti-GBM nephritis. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  10. Laminations and microgranule formation in pediatric glomerular basement membranes.

    Science.gov (United States)

    Craver, Randall; Crespo-Salgado, Janice; Aviles, Diego

    2014-01-01

    Glomerular basement membrane (GBM) splitting, laminations, and microgranular formation are classically encountered with Alport disease, but can be found in other glomerular diseases. We found moderate to marked GBM laminations/microgranular formations in 51 of 724 (7%) pediatric diagnostic renal biopsies. These included 12 Alport disease, 12 thin basement membrane disease (TBM), 13 mesangial hypercellularity (MH), 6 focal segmental glomerulosclerosis (FSGS), and 8 other diseases. Follow-up demonstrated progression in most of the Alport disease and FSGS, as expected, but also in 40% of TBM and 30% of MH. Basement membrane laminations/microgranular formations are not specific for Alport disease, may represent a non-specific injury, and may herald a progressive clinical course.

  11. 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

    2010-07-01

    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.

  12. Histopathological and ultrastructural analysis of vestibular endorgans in Meniere's disease reveals basement membrane pathology

    Directory of Open Access Journals (Sweden)

    McCall Andrew A

    2009-06-01

    Full Text Available Abstract Background We report the systematic analysis of the ultrastructural and cytological histopathology of vestibular endorgans acquired from labyrinthectomy in Meniere's disease. Methods 17 subjects with intractable Meniere's disease and ipsilateral non-serviceable hearing presenting to the Neurotology Clinic from 1997 to 2006 who chose ablative labyrinthectomy (average age = 62 years; range 29–83 years participated. The average duration of symptoms prior to surgery was 7 years (range 1–20 years. Results Nearly all vestibular endorgans demonstrated varying degrees of degeneration. A monolayer of epithelial cells occurred significantly more frequently in the horizontal cristae (12/13 = 92% (p Conclusion Systematic histopathological analysis of the vestibular endorgans from Meniere's disease demonstrated neuroepithelial degeneration which was highly correlated with an associated BM thickening. Other findings included hair cell and supporting cell microvessicles, increased intercellular clear spaces in the stroma, and endothelial cell vacuolization and stromal perivascular BM thickening.

  13. Still more complexity in mammalian basement membranes

    DEFF Research Database (Denmark)

    Erickson, A C; Couchman, J R

    2000-01-01

    At the epithelial/mesenchymal interface of most tissues lies the basement membrane (BM). These thin sheets of highly specialized extracellular matrix vary in composition in a tissue-specific manner, and during development and repair. For about two decades it has been apparent that all BMs contain...

  14. ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity.

    Science.gov (United States)

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

    2012-01-01

    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.

  15. 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

    2014-01-01

    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.

  16. Epidermal basement membrane alpha 5(IV) expression in females with Alport syndrome and severity of renal disease.

    Science.gov (United States)

    Massella, Laura; Onetti Muda, Andrea; Faraggiana, Tullio; Bette, Cristiano; Renieri, Alessandra; Rizzoni, Gianfranco

    2003-11-01

    X-linked Alport syndrome is a progressive nephritis caused by mutations of the COL4A5 gene. This gene encodes the collagen alpha 5(IV) chain, which is abnormally distributed in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). It has been reported a negative correlation between alpha 5(IV) chain distribution in EBM and the degree of proteinuria in heterozygous females with Alport syndrome. In the present study, we evaluated the distribution of the alpha 5(IV) chain in the EBM and the degree of proteinuria in 22 females with X-linked Alport syndrome. The distribution of the cutaneous alpha 5(IV) chain was measured by a confocal laser microscope using an anti-alpha 5(IV) monoclonal antibody. The expression ratio of alpha 5(IV) distribution was quantified dividing the extension of the positive signal and the maximal extension of the specimen. Urinary protein excretion was expressed as urinary protein over urinary creatinine ratio. Proteinuria was present in five of the 22 patients. In two patients with proteinuria, alpha 5(IV)chain was normally distributed; in the remaining three, the expression ratio of alpha 5(IV)chain was 35%, 47%, and 48%. Of the 17 patients without proteinuria, two displayed a complete absence of the alpha 5(IV) chain in EBM, five displayed a normal staining, and the remaining 10 had an expression ratio between 18% and 65%. Our data suggest that there is no correlation between the severity of the glomerular involvement (expressed by proteinuria) and the staining of the alpha 5 chain in the EBM in females with X-linked Alport syndrome.

  17. Antiglomerular basement membrane antibody-crescentic glomerulonephritis complicating chronic bronchiectasis.

    Science.gov (United States)

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

    2001-04-01

    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.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    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...

  19. 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;

    2007-01-01

    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....

  20. 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;

    1994-01-01

    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...

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

    OpenAIRE

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

    2012-01-01

    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...

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

    Science.gov (United States)

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

    2015-01-01

    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. 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.

    Science.gov (United States)

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

    2007-05-10

    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.

  4. A Review on the Potential Role of Basement Membrane Laminin in the Pathogenesis of Psoriasis.

    Science.gov (United States)

    McFadden, J P; Kimber, I

    2016-01-01

    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.

  5. Expression of basement membrane antigens in spindle cell melanoma.

    Science.gov (United States)

    Prieto, V G; Woodruff, J M

    1998-07-01

    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.

  6. Retinal ectopias and mechanically weakened basement membrane in a mouse model of muscle-eye-brain (MEB) disease congenital muscular dystrophy.

    Science.gov (United States)

    Hu, Huaiyu; Candiello, Joseph; Zhang, Peng; Ball, Sherry L; Cameron, David A; Halfter, Willi

    2010-07-28

    Some forms of congenital muscular dystrophy are associated with cortical and retinal dysplasias. Protein O-mannose N-acetylglucosaminyltransferase 1 (POMGnT1) knockout mice, one of the mouse models of muscular dystrophy, exhibit a thinner retina with reduced density of retinal ganglion cells. This study is aimed to further characterize the knockout retina, with special emphasis on the inner limiting membrane, the basement membrane of the retina. Immunofluorescence staining and transmission electron microscopy were used to analyze the retinas. Atomic force microscopy was performed on the inner limiting membrane preparations to examine their mechanical properties. The inner limiting membrane of the knockout mice exhibited frequent breaks with protrusions of the Müller glial processes and ectopic placement of retinal ganglion cells into the vitreous humor. Disruptions in inner limiting membrane integrity developmentally precede the cellular abnormalities. Regions of disrupted inner limiting membrane were also associated with molecular abnormalities of Müller glia that included diminished presence of the integral membrane proteins Kir4.1 (an inwardly rectifying potassium channel) and aquaporin-4. When measured with atomic force microscopy, the POMGnT1 knockout mouse inner limiting membrane (ILM) exhibited significantly reduced Young's modulus and is therefore mechanically weaker than the ILM from controls. Deficiency of POMGnT1-mediated glycosylation of dystroglycan is implicated in reduced stiffness of the ILM. The weakened ILM results in the disruption of the membrane and subsequent reduction in retinal integrity.

  7. Superficial dermal fibroblasts enhance basement membrane and epidermal barrier formation in tissue-engineered skin: implications for treatment of skin basement membrane disorders.

    Science.gov (United States)

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

    2014-02-01

    forms significantly better basement membrane with higher expression of dermo-epidermal adhesive and anchoring proteins, and superior epidermis with enhanced barrier function compared to that with deep fibroblasts and keratinocytes, or with superficial fibroblasts, deep fibroblasts, and keratinocytes. The specific use of superficial fibroblasts in tissue-engineered skin may thus be more beneficial to promote adhesion of newly formed skin and wound healing, and is therefore promising for the treatment of patients with basement membrane disorders and other skin blistering diseases.

  8. How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

    Science.gov (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

    2016-01-01

    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

  9. How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases.

    Science.gov (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

    2016-09-20

    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

  10. Vascular basement membranes as pathways for the passage of fluid into and out of the brain.

    Science.gov (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

    2016-05-01

    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.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    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 ve...

  12. Abnormal glomerular basement membrane in idiopathic multicentric osteolysis

    NARCIS (Netherlands)

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

    1996-01-01

    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

  13. Ultrastructure of basement membranes in developing shark tooth.

    Science.gov (United States)

    Sawada, T; Inoue, S

    2003-01-01

    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

  14. Study on the nature of the Goodpasture antigen using a basement membrane-producing mouse tumour.

    Science.gov (United States)

    Wick, G; Timpl, R

    1980-01-01

    Autoantibodies in the sera of patients with Goodpasture's syndrome showed a strong reaction in indirect immunofluorescence tests on unfixed, frozen sections of a mouse tumour (EHS sarcoma), previously shown to produce extracellular basement membrane. Anti-basement membrane antibodies from patients with bullous pemphigoid failed to react with the mouse tumour, but showed a distinct reaction with cylindroma tissue. Absorption of Goodpasture sera with tumour homogenate completely abolished their reaction on sections of human and murine kidney. Basement membrane (type IV) collagen and a high molecular weight, non-collagenous glycoprotein were isolated from the tumour matrix and studied in absorption experiments and radioimmunoassays. Little or not reaction was observed with Goodpasture patients' sera indicating that neither of these two proteins is the major antigen involved in the disease. Antigenic material reacting with Goodpasture sera was extracted from the tumour in neutral salt solutions, suggesting that it is a non-collagenous protein. PMID:6247110

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

    OpenAIRE

    2013-01-01

    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 ...

  16. Regulation of the basement membrane by epithelia generated forces

    Science.gov (United States)

    Tanner, Kandice

    2012-12-01

    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.

  17. Syndecan-1 deficiency aggravates anti-glomerular basement membrane nephritis.

    Science.gov (United States)

    Rops, A L; Götte, M; Baselmans, M H; van den Hoven, M J; Steenbergen, E J; Lensen, J F; Wijnhoven, T J; Cevikbas, F; van den Heuvel, L P; van Kuppevelt, T H; Berden, J H; van der Vlag, J

    2007-11-01

    During the heterologous phase of experimental anti-glomerular basement membrane (anti-GBM) nephritis, leukocyte influx peaks within hours, whereas albuminuria occurs within 1 day. In the subsequent autologous phase, endogenous anti-GBM IgG develops and albuminuria persists. Heparan sulfate (HS) proteoglycans like syndecan-1 play multiple roles during inflammation and we evaluate its role in experimental anti-GBM disease using syndecan-1 knockout (sdc-1-/-) mice. During the heterologous phase, glomerular leukocyte/macrophage influx was significantly higher in the sdc-1-/- mice and this was associated with higher glomerular endothelial expression of specific HS domains. In the autologous phase, glomerular influx of CD4+/CD8+ T cells was higher in the sdc-1-/- mice and these mice had persistently higher albuminuria and serum creatinine levels than wild-type mice. This resulted in a more sever glomerular injury and increased expression of extracellular matrix proteins. The sdc-1-/- mice developed higher plasma levels and glomerular deposits of total mouse Ig and IgG1 anti-rabbit IgG, whereas the levels of mouse IgG2a anti-rabbit IgG were lower. Furthermore, decreased Th1 and higher Th2 renal cytokine/chemokine expression were found in the sdc-1-/- mice. Our studies show that syndecan-1 deficiency exacerbates anti-GBM nephritis shifting the Th1/Th2 balance towards a Th2 response.

  18. Identification of Goodpasture target antigens in basement membranes of human glomeruli, lung, and placenta.

    Science.gov (United States)

    Weber, M; Köhler, H; Manns, M; Baum, H P; Meyer zum Büschenfelde, K H

    1987-01-01

    Collagenase-digests of human glomerular (GBM), alveolar (ABM), and placenta basement membranes (PBM) were separated by gel filtration columns and the pools rich in Goodpasture antigens (GP) were identified by an antibody inhibition-ELISA. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting on nitrocellulose membranes was performed with each basement membrane preparation. Sera from patients with florid GP-syndrome and antibodies to glomerular basement membrane (anti-GBM antibodies) were incubated with nitrocellulose strips of GBM, ABM, and PBM. Immunoperoxidase staining revealed reactivity with target antigens of 24, 26, 44, and 50 kD in the GBM and of 44 and 50 kD in the ABM and PBM, respectively. No corresponding reactivity was observed using convalescent GP-sera, sera from patients with other immunological diseases or sera from healthy blood donors. The antigens were sensitive to reduction. We conclude, that antigens of similar molecular-weights can be identified by anti-GBM positive sera in human glomerular, alveolar and placenta basement membranes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3608225

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

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R

    1990-01-01

    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....

  20. Pericapillary basement membrane thickening in human skeletal muscles.

    Science.gov (United States)

    Baum, Oliver; Bigler, Marius

    2016-09-01

    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.

  1. Membranous nephropathy, antitubular basement membrane antibodies and alveolar hemorrhage in a diabetic child.

    Science.gov (United States)

    Gallego, N; Olivares, F; Mampaso, F; Gonzalo, A; Barrio, R; Estepa, R; Ortuño, J

    1990-01-01

    We describe an 8-year-old boy who was diagnosed as having diabetes mellitus at the age of 3 months. During the follow-up the diabetes was uncontrolled, and he presented nephrotic syndrome with renal function impairment, a renal biopsy showing a membranous nephropathy. Subsequently he had episodes of anemia and dyspnea, due to alveolar hemorrhage, and he also developed Fanconi's syndrome. A later renal biopsy showed membranous glomerulonephritis and interstitial nephritis. The presence of antitubular basement membrane antibodies was noted but antialveolar basement membrane antibodies were not detected. We do not believe that this unusual clinical picture was a coincidence, and we speculate about a possible explanation.

  2. Effects of radiation on the permeability of human basement membranes

    Science.gov (United States)

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

    1999-02-01

    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

    1984-01-01

    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. Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy.

    Science.gov (United States)

    Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik

    2014-02-01

    Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.

  5. 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.

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

    Science.gov (United States)

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

    2013-01-01

    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. 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.

  8. Laminin isoforms in endothelial and perivascular basement membranes.

    Science.gov (United States)

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

    2013-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Mino,Yasuaki

    1984-10-01

    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. Identification of Goodpasture antigens in human alveolar basement membrane.

    Science.gov (United States)

    Yoshioka, K; Iseki, T; Okada, M; Morimoto, Y; Eryu, N; Maki, S

    1988-01-01

    Goodpasture (GP) antigens, protein components reactive with human autoantibodies against glomerular basement membrane (GBM), were identified in human alveolar basement membrane (ABM) using an enzyme-linked immunoassay (ELISA), Western blotting and immunoprecipitation. All six anti-GBM antisera studied, three obtained from patients with glomerulonephritis and pulmonary haemorrhages (i.e. GP syndrome), and three from patients with glomerulonephritis alone, distinctively reacted with collagenase-digested (CD) ABM. Very cationic 22-28 kD and 40-48 kD components were detected by blot analysis combined with two-dimensional gel electrophoresis. These proteins showed some similarities to GP antigens in human GBM with respect to the monomer-dimer composition and charge distribution. Inhibition ELISA revealed that the binding of anti-GBM antisera to CDGBM decreased when they were pre-incubated with CDABM, suggesting that the anti-GBM antisera recognized the same epitope(s) on the GBM and ABM. Heterogeneity of the GP antigens in human ABM was demonstrated by blotting; monomeric antigens were absent or at low levels in the CDABM of three out of 10 normal individuals. In immunoprecipitation, anti-GBM antisera from patients with and without pulmonary haemorrhage showed different reactivities with CDABM. The former antisera precipitated both monomeric and dimeric components, but the latter did not. The observations of variation in monomer-dimer composition of ABM, and the different binding of anti-GBM antisera to it may explain why only some patients with anti-GBM nephritis have lung involvement. Images Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:2466590

  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

    1991-01-01

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

    NARCIS (Netherlands)

    F.T.B. Bosman (Fré)

    1994-01-01

    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

  13. Anti-glomerular basement membrane: A rare cause of renal failure in children

    Directory of Open Access Journals (Sweden)

    Indira Agarwal

    2017-01-01

    Full Text Available Anti-glomerular basement membrane (GBM disease is a rare cause of acute renal failure and known to have bad prognosis regarding renal functions recovery and patient survival specially when diagnosed late and presents with severe renal failure that requires dialysis. We report a case of 11-year-old child with acute renal failure secondary to anti-GBM disease and associated with antineutrophil cytoplasmic antibody-positive vasculitis. He was treated with plasmapheresis, steroids, and cyclophosphamide with recovery of his kidney functions.

  14. Susceptibility to anti-glomerular basement membrane disease and Goodpasture syndrome is linked to MHC class II genes and the emergence of T cell-mediated immunity in mice.

    Science.gov (United States)

    Kalluri, R; Danoff, T M; Okada, H; Neilson, E G

    1997-11-01

    We developed a new mouse model of human anti-glomerular basement membrane (GBM) disease to better characterize the genetic determinants of cell-mediated injury. While all major histocompatibility complex (MHC) haplotypes (H-2a, k, s, b, and d) immunized with alpha3 NC1 domains of type IV collagen produce anti-alpha3(IV) NC1 antibodies that cross-react with human Goodpasture [anti-GBM/anti-alpha3(IV) NC1] autoantibodies, only a few strains developed nephritis and lung hemorrhage associated with Goodpasture syndrome. Crescentic glomerulonephritis and lung hemorrhage were MHC-restricted in haplotypes H-2s, b, and d (A beta/A alpha region in H-2s) and associated with the emergence of an IL-12/Th1-like T cell phenotype. Lymphocytes or anti-alpha3(IV) NC1 antibodies from nephritogenic strains transfer disease to syngeneic recipients. However, passive transfer of isogenic alpha3(IV) NC1 antibodies into -/- T cell receptor-deficient mice failed to produce nephritis. Finally, nephritis and its associated IL-12/Th1-like T cell response attenuate in disease-susceptible mice tolerized orally to alpha3(IV) collagen before immunization. Our findings suggest collectively, as a hypothesis, that anti-GBM antibodies in mice only facilitate disease in MHC haplotypes capable of generating nephritogenic lymphocytes with special T cell repertoires.

  15. 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;

    1995-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Idorn Thomas

    2012-07-01

    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.

  17. 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;

    1993-01-01

    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...

  18. FOS-1 promotes basement-membrane removal during anchor-cell invasion in C. elegans.

    Science.gov (United States)

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

    2005-06-17

    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.

  19. Reticular basement membrane in asthma and COPD: Similar thickness, yet different composition

    Directory of Open Access Journals (Sweden)

    Jeroen JW Liesker

    2009-02-01

    Full Text Available Jeroen JW Liesker1, Nick H Ten Hacken1, Mieke Zeinstra-Smith2, Steven R Rutgers1, Dirkje S Postma1, Wim Timens21Department of Pulmonology; 2Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Background: Reticular basement membrane (RBM thickening has been variably associated with asthma and chronic obstructive pulmonary disease (COPD. Even if RBM thickness is similar in both diseases, its composition might still differ. Objective: To assess whether RBM thickness and composition differ between asthma and COPD. Methods: We investigated 24 allergic asthmatics (forced expiratory volume in one second [FEV1] 92% predicted, and 17 nonallergic COPD patients (FEV1 60% predicted, and for each group a control group of similar age and smoking habits (12 and 10 persons, respectively. Snap-frozen sections of bronchial biopsies were stained with hematoxylin/eosin and for collagen I, III, IV, V, laminin and tenascin. RBM thickening was assessed by digital image analysis. Relative staining intensity of each matrix component was determined.Results: Mean (SD RBM thickness was not significantly different between asthma and COPD 5.5 (1.3 vs 6.0 (1.8 μm, but significantly larger than in their healthy counterparts, ie, 4.7 (0.9 and 4.8 (1.2 μm, respectively. Collagen I and laminin stained significantly stronger in asthma than in COPD. Tenascin stained stronger in asthma than in healthy controls of similar age, and stronger in COPD controls than in asthma controls (p 0.05.Conclusion: RBM thickening occurs both in asthma and COPD. We provide supportive evidence that its composition differs in asthma and COPD. Keywords: reticular basement membrane thickness, reticular basement membrane composition, asthma, biopsy, COPD, remodeling

  20. 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;

    1996-01-01

    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...

  1. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis

    NARCIS (Netherlands)

    Rutgers, Abraham; Slot, Marjan; van Paassen, Pieter; van Breda Vriesman, Peter; Heeringa, Peter; Tervaert, Jan Willem Cohen

    2005-01-01

    BACKGROUND: In a substantial proportion of patients with crescentic glomerulonephritis (CGN), both anti-glomerular basement membrane (GBM) antibodies and antineutrophil cytoplasmic antibodies (ANCAs) with specificity for myeloperoxidase (MPO-ANCA) are detected. In the present study, we questioned wh

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

    Directory of Open Access Journals (Sweden)

    Kentaro Hozumi

    2015-02-01

    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.

  3. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis

    NARCIS (Netherlands)

    Rutgers, Abraham; Slot, Marjan; van Paassen, Pieter; van Breda Vriesman, Peter; Heeringa, Peter; Tervaert, Jan Willem Cohen

    BACKGROUND: In a substantial proportion of patients with crescentic glomerulonephritis (CGN), both anti-glomerular basement membrane (GBM) antibodies and antineutrophil cytoplasmic antibodies (ANCAs) with specificity for myeloperoxidase (MPO-ANCA) are detected. In the present study, we questioned

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

    OpenAIRE

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

    2002-01-01

    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...

  5. Goodpasture antigen of the glomerular basement membrane: localization to noncollagenous regions of type IV collagen.

    Science.gov (United States)

    Wieslander, J; Barr, J F; Butkowski, R J; Edwards, S J; Bygren, P; Heinegård, D; Hudson, B G

    1984-01-01

    The glomerular basement membrane antigen in Goodpasture syndrome is a collagenase-resistant molecule with a monomer molecular weight of about 26,000. Type IV collagen isolated from glomerular basement membrane contains collagenase-resistant sequences within its structure. Polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay, and chemical analysis were used to demonstrate that the collagenase-resistant sequences of type IV collagen contain Goodpasture antigen. Images PMID:6328527

  6. Goodpasture’s Syndrome with Negative Anti-glomerular Basement Membrane Antibodies

    Directory of Open Access Journals (Sweden)

    Tjitske Berends-De Vries

    2017-07-01

    Full Text Available A young male patient with rapidly progressive and life-threatening pulmonary haemorrhage due to anti-glomerular basement membrane (anti-GBM antibody disease without renal involvement repeatedly tested negative for serum anti-GBM antibodies. Although rare, anti-GBM antibody disease should be considered in the differential diagnosis in patients with life-threatening pulmonary haemorrhage due to isolated diffuse alveolar haemorrhage. Enzyme-linked-immunosorbent assay (ELISA testing for anti-GBM antibodies in anti-GBM antibody disease can give false-negative results. A negative serum anti-GBM antibody test is therefore insufficient to exclude the diagnosis. Thus, a kidney or lung biopsy should be considered in any case with a high clinical suspicion but negative anti-GBM antibody test to confirm or rule out the diagnosis.

  7. Basement membrane abnormalities in human eyes with diabetic retinopathy

    DEFF Research Database (Denmark)

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

    1996-01-01

    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....

  8. Transplacental transmission of antibodies to tubular basement membrane in guinea-pigs with autoimmune tubulointerstitial nephritis.

    Science.gov (United States)

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

    1984-04-01

    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.

  9. Antiglomerular basement membrane antibody-mediated glomerulonephritis after intranasal cocaine use.

    Science.gov (United States)

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

    1999-01-01

    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.

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

    DEFF Research Database (Denmark)

    Couchman, J R; Gibson, W T

    1985-01-01

    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...... membrane and connective tissue sheath, which undergo corrugation and apparent thickening in catagen. After follicle shortening, the telogen (resting) stage is reached, at which point fibronectin staining was found to be minimal, being restricted to the basement membrane around the secondary germ. The onset...... the increase in fibronectin expression. However, growing cells, even in a suprabasal position, always had some fibronectin at their surface. Immunoelectron microscopy of early anagen follicles confirmed the light microscopic findings and also showed that fibronectin was present in small vesicles close...

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

    DEFF Research Database (Denmark)

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

    1989-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Ichiyasu,Akira

    1988-12-01

    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.

  13. 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

    1986-01-01

    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...... and one patient with Cushing's syndrome). Concurrently, at the ultrastructural level, bunches of basement membrane-like material intermingled between the adenoma cells were demonstrated in seven of these ten active adenomas. Furthermore, secretory granules were entrapped occasionally in this intercellular...... matrix, indicating a mutual dependence between excessive hormone extrusion and an increase of "misplaced" deposits of basement membrane components, e.g., laminin....

  14. 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

    1981-01-01

    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...... and in their basement membranes suggesting, but not proving, that both types of cells have ability to synthesize laminin. Production of laminin and the presence of laminin-containing basement membrane material may be important for the biological behavior of the yolk sac tumor. This tumor will also be a useful source...

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

    DEFF Research Database (Denmark)

    Couchman, J R

    1986-01-01

    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...

  16. 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

    1991-01-01

    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....

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

    DEFF Research Database (Denmark)

    Couchman, J R

    1987-01-01

    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...

  18. 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)

    1999-02-01

    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.

  19. 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.

  20. Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice.

    Science.gov (United States)

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

    2012-07-01

    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.

  1. 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

    1991-01-01

    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...

  2. 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.

    2015-01-01

    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

  3. 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

    2006-01-01

    , 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....

  4. 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;

    2015-01-01

    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...

  5. 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.

    1985-01-01

    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

  6. Drosophila laminins act as key regulators of basement membrane assembly and morphogenesis.

    Science.gov (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

    2009-12-01

    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.

  7. Ultrastructure of basement membranes in monkey and shark teeth at an early stage of development.

    Science.gov (United States)

    Sawada, Takashi

    2003-12-01

    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.

  8. Hypoplastic basement membrane of the lens anlage in the inheritable lens aplastic mouse (lap mouse).

    Science.gov (United States)

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

    2000-04-01

    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

  9. Isotropic Versus Bipolar Functionalized Biomimetic Artificial Basement Membranes and Their Evaluation in Long-Term Human Cell Co-Culture.

    Science.gov (United States)

    Rossi, Angela; Wistlich, Laura; Heffels, Karl-Heinz; Walles, Heike; Groll, Jürgen

    2016-08-01

    In addition to dividing tissues into compartments, basement membranes are crucial as cell substrates and to regulate cellular behavior. The development of artificial basement membranes is indispensable for the ultimate formation of functional engineered tissues; however, pose a challenge due to their complex structure. Herein, biodegradable electrospun polyester meshes are presented, exhibiting isotropic or bipolar bioactivation as a biomimetic and biofunctional model of the natural basement membrane. In a one-step preparation process, reactive star-shaped prepolymer additives, which generate a hydrophilic fiber surface, are electrospun with cell-adhesion-mediating peptides, derived from major components of the basement membrane. Human skin cells adhere to the functionalized meshes, and long-term co-culture experiments confirm that the artificial basement membranes recapitulate and preserve tissue specific functions. Several layers of immortalized human keratinocytes grow on the membranes, differentiating toward the surface and expressing typical epithelial markers. Fibroblasts migrate into the reticular lamina mimicking part of the mesh. Both cells types begin to produce extracellular matrix proteins and to remodel the initial membrane. It is shown at the example of skin that the artificial basement membrane design provokes biomimetic responses of different cell types and can thus be used as basis for the future development of basement membrane containing tissues. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Directory of Open Access Journals (Sweden)

    Koon-Ja Lee

    2013-04-01

    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

  11. 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

    1985-01-01

    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...

  12. Integrating Activities of Laminins that Drive Basement Membrane Assembly and Function.

    Science.gov (United States)

    Yurchenco, Peter D

    2015-01-01

    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.

  13. Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of the oral mucosa.

    Science.gov (United States)

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

    2010-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Bjermer Leif

    2006-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Pirjo Spuul

    2016-10-01

    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.

  16. Uncommon structural motifs dominate the antigen binding site in human autoantibodies reactive with basement membrane collagen.

    Science.gov (United States)

    Foster, Mary H; Buckley, Elizabeth S; Chen, Benny J; Hwang, Kwan-Ki; Clark, Amy G

    2016-08-01

    Autoantibodies mediate organ destruction in multiple autoimmune diseases, yet their origins in patients remain poorly understood. To probe the genetic origins and structure of disease-associated autoantibodies, we engrafted immunodeficient mice with human CD34+ hematopoietic stem cells and immunized with the non-collagenous-1 (NC1) domain of the alpha3 chain of type IV collagen. This antigen is expressed in lungs and kidneys and is targeted by autoantibodies in anti-glomerular basement membrane (GBM) nephritis and Goodpasture syndrome (GPS), prototypic human organ-specific autoimmune diseases. Using Epstein Barr virus transformation and cell fusion, six human anti-alpha3(IV)NC1 collagen monoclonal autoantibodies (mAb) were recovered, including subsets reactive with human kidney and with epitopes recognized by patients' IgG. Sequence analysis reveals a long to exceptionally long heavy chain complementarity determining region3 (HCDR3), the major site of antigen binding, in all six mAb. Mean HCDR3 length is 25.5 amino acids (range 20-36), generated from inherently long DH and JH genes and extended regions of non-templated N-nucleotides. Long HCDR3 are suited to forming noncontiguous antigen contacts and to binding recessed, immunologically silent epitopes hidden from conventional antibodies, as seen with self-antigen crossreactive broadly neutralizing anti-HIV Ig (bnAb). The anti-alpha3(IV)NC1 collagen mAb also show preferential use of unmutated variable region genes that are enriched among human chronic lymphocytic leukemia antibodies that share features with natural polyreactive Ig. Our findings suggest unexpected relationships between pathogenic anti-collagen Ig, bnAb, and autoreactive Ig associated with malignancy, all of which arise from B cells expressing unconventional structural elements that may require transient escape from tolerance for successful expansion. Published by Elsevier Ltd.

  17. Uncommon Structural Motifs Dominate the Antigen Binding Site in Human Autoantibodies Reactive with Basement Membrane Collagen

    Science.gov (United States)

    Foster, Mary H.; Buckley, Elizabeth S.; Chen, Benny J.; Hwang, Kwan-Ki; Clark, Amy G.

    2016-01-01

    Autoantibodies mediate organ destruction in multiple autoimmune diseases, yet their origins in patients remain poorly understood. To probe the genetic origins and structure of disease-associated autoantibodies, we engrafted immunodeficient mice with human CD34+ hematopoietic stem cells and immunized with the non-collagenous-1 (NC1) domain of the alpha3 chain of type IV collagen. This antigen is expressed in lungs and kidneys and is targeted by autoantibodies in anti-glomerular basement membrane (GBM) nephritis and Goodpasture syndrome (GPS), prototypic human organ-specific autoimmune diseases. Using Epstein Barr virus transformation and cell fusion, six human anti-alpha3(IV)NC1 collagen monoclonal autoantibodies (mAb) were recovered, including subsets reactive with human kidney and with epitopes recognized by patients’ IgG. Sequence analysis reveals a long to exceptionally long heavy chain complementarity determining region3 (HCDR3), the major site of antigen binding, in all six mAb. Mean HCDR3 length is 25.5 amino acids (range 20–36), generated from inherently long DH and JH genes and extended regions of non-templated N-nucleotides. Long HCDR3 are suited to forming noncontiguous antigen contacts and to binding recessed, immunologically silent epitopes hidden from conventional antibodies, as seen with self-antigen crossreactive broadly neutralizing anti-HIV Ig (bnAb). The anti-alpha3(IV)NC1 collagen mAb also show preferential use of unmutated variable region genes that are enriched among human chronic lymphocytic leukemia antibodies that share features with natural polyreactive Ig. Our findings suggest unexpected relationships between pathogenic anti-collagen Ig, bnAb, and autoreactive Ig associated with malignancy, all of which arise from B cells expressing unconventional structural elements that may require transient escape from tolerance for successful expansion. PMID:27450516

  18. Label-free imaging of basement membranes differentiates normal, precancerous, and cancerous colonic tissues by second-harmonic generation microscopy.

    Science.gov (United States)

    Zhuo, Shuangmu; Yan, Jun; Chen, Gang; Shi, Hong; Zhu, Xiaoqin; Lu, Jianping; Chen, Jianxin; Xie, Shusen

    2012-01-01

    Since changes in the basement membranes are the critical indicators for differentiating normal, precancerous, and cancerous colonic tissues, direct visualization of these warning signs is essential for the early diagnosis and treatment of colonic cancer. Here, we present that second harmonic generation (SHG) microscopy can probe the changes of basement membranes in different colonic cancer stages. Our results also show the capability of using the quantitative analyses of images for quantifying these changes in different cancer stages. These results suggest that SHG microscopy has the potential in label-freely imaging the changes of basement membranes for effectively distinguishing between normal, precancerous, and cancerous colonic tissues. To our knowledge, this is the first demonstration of the dynamics of basement membrane changes in different colonic cancer stages using entirely intrinsic source of contrast.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hori, I.

    1979-03-01

    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.

  20. 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

    1991-01-01

    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...

  1. Type XV collagen in human colonic adenocarcinomas has a different distribution than other basement membrane zone proteins.

    Science.gov (United States)

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

    2000-03-01

    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

  2. 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

    1988-01-01

    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 (correspond......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...

  3. Protein composition and biomechanical properties of in vivo-derived basement membranes.

    Science.gov (United States)

    Halfter, Willi; Candiello, Joseph; Hu, Haiyu; Zhang, Peng; Schreiber, Emanuel; Balasubramani, Manimalha

    2013-01-01

    Basement membranes (BMs) evolved together with the first metazoan species approximately 500 million years ago. Main functions of BMs are stabilizing epithelial cell layers and connecting different types of tissues to functional, multicellular organisms. Mutations of BM proteins from worms to humans are either embryonic lethal or result in severe diseases, including muscular dystrophy, blindness, deafness, kidney defects, cardio-vascular abnormalities or retinal and cortical malformations. In vivo-derived BMs are difficult to come by; they are very thin and sticky and, therefore, difficult to handle and probe. In addition, BMs are difficult to solubilize complicating their biochemical analysis. For these reasons, most of our knowledge of BM biology is based on studies of the BM-like extracellular matrix (ECM) of mouse yolk sac tumors or from studies of the lens capsule, an unusually thick BM. Recently, isolation procedures for a variety of BMs have been described, and new techniques have been developed to directly analyze the protein compositions, the biomechanical properties and the biological functions of BMs. New findings show that native BMs consist of approximately 20 proteins. BMs are four times thicker than previously recorded, and proteoglycans are mainly responsible to determine the thickness of BMs by binding large quantities of water to the matrix. The mechanical stiffness of BMs is similar to that of articular cartilage. In mice with mutation of BM proteins, the stiffness of BMs is often reduced. As a consequence, these BMs rupture due to mechanical instability explaining many of the pathological phenotypes. Finally, the morphology and protein composition of human BMs changes with age, thus BMs are dynamic in their structure, composition and biomechanical properties.

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

    Science.gov (United States)

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

    2009-03-27

    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.

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

    DEFF Research Database (Denmark)

    Fenger, M; Wewer, U; Albrechtsen, R

    1984-01-01

    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....

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

    DEFF Research Database (Denmark)

    Fenger, M; Wewer, U; Albrechtsen, R

    1984-01-01

    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....

  7. Creatinine clearance, urinary excretion of glomerular basement membrane antigens and renal histology in congenital nephrotic syndrome of Finnish type.

    Science.gov (United States)

    Huttunen, N P

    1977-04-01

    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.

  8. An in vitro model of the glomerular capillary wall using electrospun collagen nanofibres in a bioartificial composite basement membrane.

    Directory of Open Access Journals (Sweden)

    Sadie C Slater

    Full Text Available The filtering unit of the kidney, the glomerulus, contains capillaries whose walls function as a biological sieve, the glomerular filtration barrier. This comprises layers of two specialised cells, glomerular endothelial cells (GEnC and podocytes, separated by a basement membrane. Glomerular filtration barrier function, and dysfunction in disease, remains incompletely understood, partly due to difficulties in studying the relevant cell types in vitro. We have addressed this by generation of unique conditionally immortalised human GEnC and podocytes. However, because the glomerular filtration barrier functions as a whole, it is necessary to develop three dimensional co-culture models to maximise the benefit of the availability of these cells. Here we have developed the first two tri-layer models of the glomerular capillary wall. The first is based on tissue culture inserts and provides evidence of cell-cell interaction via soluble mediators. In the second model the synthetic support of the tissue culture insert is replaced with a novel composite bioartificial membrane. This consists of a nanofibre membrane containing collagen I, electrospun directly onto a micro-photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in monolayers on either side of the insert support or the novel membrane to form a tri-layer model recapitulating the human glomerular capillary in vitro. These models will advance the study of both the physiology of normal glomerular filtration and of its disruption in glomerular disease.

  9. Nephritogenic lupus antibodies recognize glomerular basement membrane-associated chromatin fragments released from apoptotic intraglomerular cells.

    Science.gov (United States)

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

    2006-06-01

    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.

  10. 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.

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

    Science.gov (United States)

    Zelman, M E; Lange, C F

    1989-09-01

    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.

  12. Sequential development of pulmonary hemorrhage with MPO-ANCA complicating anti-glomerular basement membrane antibody-mediated glomerulonephritis.

    Science.gov (United States)

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

    2000-05-01

    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.

  13. Breaches of the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies.

    Science.gov (United States)

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

    2011-11-07

    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.

  14. 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

    1992-01-01

    -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......-membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases....

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

    Directory of Open Access Journals (Sweden)

    Yamasaki,Yasushi

    1990-12-01

    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.

  16. [Relationship between the changes in ischemia/reperfusion cerebro-microvessel basement membrane injury and gelatinase system in senile rat].

    Science.gov (United States)

    Li, Jian-sheng; Liu, Ke; Liu, Jing-xia; Wang, Ming-hang; Zhao, Yue-wu; Liu, Zheng-guo

    2008-11-01

    To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion (I/R) in aged rats. 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 [ischemia 3 hours (I 3 h) and reperfusion 6 hours (I/R 6 h), 12 hours (I/R 12 h), 24 hours (I/R 24 h), 3 days (I/R 3 d), 6 days (I/R 6 d)], and sham control group and I/R group in aged rats (I 3 h and I/R 6 h, I/R 12 h, I/R 24 h , I/R 3 d, I/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 immunohistochemical method and zymogram analysis. With the increase 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 (I 3 h, I/R 6-24 h), MMP-2 (I 3 h, I/R 6 h-6 d) and MMP-9 (I 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 (Pcerebro-microvessel basement membrane in rats is related with MMPs and TIMP. Cerebro-microvessel basement membrane injury is more serious in aged rats than that of young rats. Changes in cerebro-microvessel basement membrane injury in aged rats is related with gelatinase system change.

  17. Investigation of basement membrane proteins in a case of granular cell ameloblastoma

    Science.gov (United States)

    Lapthanasupkul, Puangwan; Poomsawat, Sopee; Chindasombatjaroen, Jira

    2012-01-01

    Granular cell ameloblastoma is a rare, benign neoplasm of the odontogenic epithelium. A case of massive granular cell ameloblastoma in a 44-year-old Thai female is reported. Histopathological features displayed a follicular type of ameloblastoma with an accumulation of granular cells residing within the tumor follicles. After treatment by partial mandibulectomy, the patient showed a good prognosis without recurrence in a 2-year follow-up. To characterize the granular cells in ameloblastoma, we examined the expression of basement membrane (BM) proteins, including collagen type IV, laminins 1 and 5 and fibronectin using immunohistochemistry. Except for the granular cells, the tumor cells demonstrated a similar expression of BM proteins compared to follicular and plexiform ameloblastomas in our previous study, whereas the granular cells showed strong positivity to laminins 1 and 5 and fibronectin. The increased fibronectin expression in granular cells suggests a possibility of age-related transformation of granular cells in ameloblastoma. PMID:22361945

  18. Removal of heparan sulfate from the glomerular basement membrane blocks protein passage.

    Science.gov (United States)

    Wijnhoven, Tessa J M; Lensen, Joost F M; Wismans, Ronnie G P; Lefeber, Dirk J; Rops, Angelique L W M M; van der Vlag, Johan; Berden, Jo H M; van den Heuvel, Lambert P W J; van Kuppevelt, Toin H

    2007-12-01

    Heparan sulfate (HS) within the glomerular basement membrane (GBM) is thought to play a major role in the charge-selective properties of the glomerular capillary wall. Recent data, however, raise questions regarding the direct role of HS in glomerular filtration. For example, in situ studies suggest that HS may prevent plasma macromolecules from clogging the GBM, keeping it in an "open" state. We evaluated this potential role of HS in vivo by studying the passage of protein through the glomerular capillary wall in the presence and absence of HS. Intravenous administration of neuraminidase removed neuraminic acid--but not HS--from the GBM, and this led to albuminuria. Concomitant removal of HS with heparinase III, confirmed by ultrastructural imaging, prevented the development of albuminuria in response to neuraminidase treatment. Taken together, these results suggest that HS keeps the GBM in an open state, facilitating passage of proteins through the glomerular capillary wall.

  19. Cell invasion through basement membrane: the anchor cell breaches the barrier.

    Science.gov (United States)

    Hagedorn, Elliott J; Sherwood, David R

    2011-10-01

    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.

  20. A rapid assay for circulating anti-glomerular basement membrane antibodies in Goodpasture syndrome.

    Science.gov (United States)

    Saxena, R; Isaksson, B; Bygren, P; Wieslander, J

    1989-03-10

    A rapid ELISA for the detection of circulating anti-glomerular basement membrane antibodies in Goodpasture syndrome is described. The specificity of the test was shown to be highly dependent on the antigens used. Using the purified Goodpasture antigen it was possible to shorten the incubation times to 10 min in a routine assay using alkaline phosphatase-labeled second antibodies and the total assay was complete in 30 min. 200 reference sera, 500 sera from patients with various types of glomerulonephritis and 32 sera from patients with Goodpasture syndrome were analyzed by this rapid assay. The assay was able to discriminate between Goodpasture syndrome and other forms of glomerulonephritis. Using enzyme amplification it was possible to further shorten the incubation times to 1 min and the total time of the assay to 6 min.

  1. Isolation of the specific glomerular basement membrane antigen involved in Goodpasture syndrome.

    Science.gov (United States)

    Wieslander, J; Bygren, P; Heinegård, D

    1984-01-01

    The antigen involved in the glomerulonephritis associated with antibodies to glomerular basement membrane (GBM) was purified from human GBM digested with highly purified clostridial collagenase. The purified nonreduced sample contained two components with closely similar mobilities on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. After reduction they moved as one, nonantigenic, component, corresponding to a molecular weight of 26,000. Immunologically identical aggregates of higher molecular weight (i.e., 48,000) were also identified in the crude digest. Reduction of such aggregates after purification released some protein with a molecular weight of 26,000, but a large proportion was insensitive to reduction. Seven patients with Goodpasture syndrome all had circulating anti-GBM antibodies directed only against the purified antigen. Images PMID:6324201

  2. 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.

    1989-03-01

    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.

  3. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy.

    Science.gov (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

    2011-06-01

    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.

  4. 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

    1990-01-01

    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 embry...

  5. 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

    1990-01-01

    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...

  6. Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

    Science.gov (United States)

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

    2007-10-01

    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.

  7. 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

    2001-01-01

    Multiple proteoglycans (PGs) are present in all basement membranes (BM) and may contribute to their structure and function, but their effects on cell behavior are not well understood. Their postulated functions include: a structural role in maintaining tissue histoarchitecture, or aid in selectiv...

  8. 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

    2014-01-01

    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

  9. 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

    2014-01-01

    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

  10. 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

    2005-01-01

    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

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

    Science.gov (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...

  12. Corneal Molecular and Cellular Biology for the Refractive Surgeon: The Critical Role of the Epithelial Basement Membrane.

    Science.gov (United States)

    Marino, Gustavo K; Santhiago, Marcony R; Torricelli, Andre A M; Santhanam, Abirami; Wilson, Steven E

    2016-02-01

    To provide an overview of the recent advances concerning the corneal molecular and cellular biology processes involved in the wound healing response after excimer laser surface ablation and LASIK surgery. Literature review. The corneal wound healing response is a complex cascade of events that impacts the predictability and stability of keratorefractive surgical procedures such as photorefractive keratectomy and LASIK. The generation and persistence of corneal myofibroblasts (contractile cells with reduced transparency) arise from the interaction of cytokines and growth factors such as transforming growth factor beta and interleukin 1 produced by epithelial and stromal cells in response to the corneal injury. Myofibroblasts, and the opaque extracellular matrix they secrete into the stroma, disturb the precise distribution and spacing of collagen fibers related to corneal transparency and lead to the development of vision-limiting corneal opacity (haze). The intact epithelial basement membrane has a pivotal role as a structure that regulates corneal epithelial-stromal interactions. Thus, defective regeneration of the epithelial basement membrane after surgery, trauma, or infection leads to the development of stromal haze. The apoptotic process following laser stromal ablation, which is proportional to the level of attempted correction, leads to an early decrease in anterior keratocyte density and the diminished contribution of these non-epithelial cells of components such as perlecan and nidogen-2 required for normal regeneration of the epithelial basement membrane. Haze persists until late repair of the defective epithelial basement membrane. Defective regeneration of the epithelial basement membrane has a critical role in determining whether a cornea heals with late haze after photorefractive keratectomy or with scarring at the flap edge in LASIK. Copyright 2016, SLACK Incorporated.

  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: roy.zent@vanderbilt.edu [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)

    2010-10-15

    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)

    BARCELLOS-HOFF, M. H; AGGELER, J.; RAM, T. G; BISSELL, M. J

    1989-02-01

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

    Science.gov (United States)

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

    2017-01-01

    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. Antiproteinuric effect of pirfenidone in a rat model of anti-glomerular basement membrane glomerulonephritis.

    Science.gov (United States)

    Takakura, Koji; Mizukami, Kazuhiko; Mitori, Hikaru; Noto, Takahisa; Tomura, Yuichi

    2014-08-15

    While pirfenidone has been established as an effective anti-fibrosis remedy, whether or not its antifibrotic effect contributes to a reduction of proteinuria remains unclear. We investigated the renoprotective properties of pirfenidone in an anti-glomerular basement membrane (GBM) glomerulonephritis model both prophylactically and therapeutically to determine its profile against proteinuria. In the prophylactic regimen, pirfenidone was treated immediately after anti-serum injection. We observed a significant reduction in the progression of proteinuria (Ppirfenidone treatment may have resulted in the decrease of proteinuria. In contrast, when the therapeutic regimen was initiated 2 weeks after nephritis induction, pirfenidone had little effect on the progression of proteinuria, although the decline of renal function and fibrosis were suppressed. Taken together, present findings suggested that pirfenidone prevented the progression of proteinuria only when administered prophylactically but was still able to ameliorate the decline of renal function independent of proteinuria. In conclusion, pirfenidone as a prophylactic regimen reduces proteinuria in anti-GBM nephritis via preservation of podocytes with markedly reduced efficacy when administered as a therapeutic regimen.

  17. 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.

  18. Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma.

    Science.gov (United States)

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

    2016-06-15

    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.

  19. Role of the basement membrane in regulation of cardiac electrical properties.

    Science.gov (United States)

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

    2014-06-01

    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.

  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

    2006-01-01

    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. Does Tensile Rupture of Tumor Basement Membrane Mark the Onset of Cancer Metastasis?

    Science.gov (United States)

    Prakash, Sai

    2015-03-01

    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.

  2. Numerical analysis of viscous flow through fibrous media: a model for glomerular basement membrane permeability.

    Science.gov (United States)

    Palassini, M; Remuzzi, A

    1998-01-01

    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.

  3. Development of the follicular basement membrane during human gametogenesis and early folliculogenesis.

    Science.gov (United States)

    Heeren, A Marijne; van Iperen, Liesbeth; Klootwijk, Daniëlle B; de Melo Bernardo, Ana; Roost, Matthias S; Gomes Fernandes, Maria M; Louwe, Leonie A; Hilders, Carina G; Helmerhorst, Frans M; van der Westerlaken, Lucette A J; Chuva de Sousa Lopes, Susana M

    2015-01-21

    In society, there is a clear need to improve the success rate of techniques to restore fertility. Therefore a deeper knowledge of the dynamics of the complex molecular environment that regulates human gametogenesis and (early) folliculogenesis in vivo is necessary. Here, we have studied these processes focusing on the formation of the follicular basement membrane (BM) in vivo. The distribution of the main components of the extracellular matrix (ECM) collagen IV, laminin and fibronectin by week 10 of gestation (W10) in the ovarian cortex revealed the existence of ovarian cords and of a distinct mesenchymal compartment, resembling the organization in the male gonads. By W17, the first primordial follicles were assembled individually in that (cortical) mesenchymal compartment and were already encapsulated by a BM of collagen IV and laminin, but not fibronectin. In adults, in the primary and secondary follicles, collagen IV, laminin and to a lesser extent fibronectin were prominent in the follicular BM. The ECM-molecular niche compartimentalizes the female gonads from the time of germ cell colonization until adulthood. This knowledge may contribute to improve methods to recreate the environment needed for successful folliculogenesis in vitro and that would benefit a large number of infertility patients.

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

    Directory of Open Access Journals (Sweden)

    Eduardo José Bellotto Monteiro

    2006-02-01

    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. Chitosan facilitates structure formation of the salivary gland by regulating the basement membrane components.

    Science.gov (United States)

    Yang, Tsung-Lin; Hsiao, Ya-Chuan

    2015-10-01

    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.

  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

    1990-01-01

    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. 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;

    1994-01-01

    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...

  8. 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

    2015-01-01

    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...

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

    OpenAIRE

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

    2009-01-01

    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. Comprehensive Characterization of Glycosylation and Hydroxylation of Basement Membrane Collagen IV by High-Resolution Mass Spectrometry.

    Science.gov (United States)

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

    2016-01-04

    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.

  11. Complement and Humoral Adaptive Immunity in the Human Choroid Plexus: Roles for Stromal Concretions, Basement Membranes, and Epithelium.

    Science.gov (United States)

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

    2016-05-01

    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.

  12. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: a comparison of different assays.

    Science.gov (United States)

    Sinico, Renato Alberto; Radice, Antonella; Corace, Caterina; Sabadini, Ettore; Bollini, Bruna

    2006-02-01

    The role of anti-glomerular basement membrane (GBM) antibodies in the pathogenesis of Goodpasture syndrome (GPS) is firmly established. Untreated, the disease may follow a fulminating course. Early identification of patients has important implications in terms of management and prognosis. Therefore, a diagnostic test for the determination of circulating anti-GBM antibodies, of very high sensitivity and specificity, is necessary. A number of assays, using different antigenic substrates, are available, but studies comparing the 'performances' of the different tests are scarce. The aim of our work was to evaluate the sensitivity and specificity of four immunoassay-based anti-GBM antibodies kits. Thirty-four serum samples from 19 GPS patients, 41 pathological and 28 normal controls were studied retrospectively (the follow-up samples were not included in the analysis of performance data). Cut-off limits were derived from receiver operating characteristics curve analysis. All the assays showed a comparable good sensitivity (between 94.7 and 100.0%), whereas specificity varied considerably (from 90.9 to 100.0%). The better performance in terms of sensitivity/specificity was achieved by a fluorescence immunoassay which utilizes a recombinant antigen. All the assays have a good performance, with high sensitivity; however, the specificity may vary considerably.

  13. IgE basement membrane zone antibodies induce eosinophil infiltration and histological blisters in engrafted human skin on SCID mice.

    Science.gov (United States)

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

    2007-05-01

    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.

  14. Putative role of basement membrane for dentinogenesis in the mesenchyme of murine dental papillae in vitro.

    Science.gov (United States)

    Kikuchi, H; Amano, H; Yamada, S

    2001-01-01

    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.

  15. Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules

    Science.gov (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

    2017-01-01

    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

  16. The effect of asthma on the perimeter of the airway basement membrane.

    Science.gov (United States)

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

    2015-11-15

    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.

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

    Directory of Open Access Journals (Sweden)

    Akishi Momose

    2015-02-01

    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.

  18. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

    Science.gov (United States)

    Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

    2014-01-01

    Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional

  19. The deformation matrix theory of basement membrane: a study of water flow through elastic and rigid filaments in the rat.

    Science.gov (United States)

    Fisher, R F

    1988-01-01

    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

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

    Science.gov (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

  1. Differential expression of epithelial basement membrane components nidogens and perlecan in corneal stromal cells in vitro.

    Science.gov (United States)

    Santhanam, Abirami; Torricelli, Andre A M; Wu, Jiahui; Marino, Gustavo K; Wilson, Steven E

    2015-01-01

    The purpose of this study was to examine the expression of corneal epithelial basement membrane (EBM) components in different corneal stromal cell types. In vitro model systems were used to explore the expression of EBM components nidogen-1, nidogen-2, and perlecan that are the primary components in the lamina lucida and the lamina densa that defectively regenerate in corneas with stromal opacity after in -9.0 D photorefractive keratectomy (PRK). Primary rabbit corneal stromal cells were cultured using varying serum concentrations and exogenous growth factors, including fibroblast growth factor (FGF)-2 and transforming growth factor (TGF)-β1, to optimize the growth of each cell type of interest. The expression of the keratocyte-specific marker keratocan and the myofibroblast-specific marker α-smooth muscle actin (α-SMA) were analyzed with real-time PCR, western blot, and immunocytochemical staining to evaluate the specificity of the cell types and select optimal conditions (high keratocan and low α-SMA for keratocytes; low keratocan and high α-SMA for myofibroblasts; low keratocan and low α-SMA for corneal fibroblasts). The expression of the EBM components nidogen-1, nidogen-2, and perlecan was evaluated in each corneal cell type using real-time PCR, immunostaining, and western blotting. In agreement with previous studies, serum-free DMEM was found to be optimal for keratocytes, DMEM with 10% serum and 40 ng/ml FGF-2 yielded the best marker profile for corneal fibroblasts, and DMEM with 1% serum and 2 ng/ml TGF-β1 was found to be optimal for myofibroblasts. Nidogen-1 and nidogen-2 mRNAs were highly expressed in keratocytes, whereas perlecan was highly expressed in myofibroblasts. In keratocytes, nidogen-2 and perlecan proteins were expressed predominantly in intracellular compartments, whereas in myofibroblasts expression of both EBM components was observed diffusely throughout the cell. Although the perlecan mRNA levels were high in the myofibroblasts, the

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

    Directory of Open Access Journals (Sweden)

    Kobayashi A

    2012-07-01

    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

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

    OpenAIRE

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

    2013-01-01

    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...

  4. Basement Membrane Mimics of Biofunctionalized Nanofibers for a Bipolar-Cultured Human Primary Alveolar-Capillary Barrier Model.

    Science.gov (United States)

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

    2017-03-13

    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.

  5. An unusual case of pulmonary-renal syndrome associated with defects in type IV collagen composition and anti-glomerular basement membrane autoantibodies.

    Science.gov (United States)

    Charytan, David; MacDonald, Brian; Sugimoto, Hikaru; Pastan, Stephen; Staton, Gerald; Hennigar, Randy; Kalluri, Raghu

    2005-04-01

    Commercial serological assays for the presence of anti-glomerular basement membrane (GBM) antibodies are thought to be indicative of Goodpasture's syndrome. We report a case in which commercial tests inaccurately suggested that a patient with a pulmonary-renal syndrome had Goodpasture's disease. Additional laboratory testing using recombinant type IV collagen NC1 domain proteins showed that the autoantibodies in question were not directed against the Goodpasture antigen (the alpha3NC1 domain), but against the alpha2NC1 domain of type IV collagen. Our findings represent the first known case of human autoantibodies to the alpha2NC1 domain. Further investigation showed that this patient has decreased alpha3 and alpha5 chain expression in the GBM and defects in type IV collagen, resembling abnormalities in patients with Alport's syndrome.

  6. 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

    1997-01-01

    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...

  7. 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;

    2017-01-01

    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....

  8. Disease: H00579 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available o the missense mutations in the COL4A1 in basement membranes. The renal manifestations include hematuria and...94725 (description, gene) Gubler MC Inherited diseases of the glomerular basement...ic disorders of glomerular basement membranes. Nephron Clin Pract 118:c9-c18 (2011) PMID:18160688 (gene) Pla

  9. 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

    2013-01-01

    We provide the first comprehensive analysis of the extracellular matrix (ECM) composition of peri-islet capsules, composed of the peri-islet basement membrane (BM) and subjacent interstitial matrix (IM), in development of type 1 diabetes in NOD mice and in human type 1 diabetes. Our data...... 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...... IM are reconstituted once inflammation subsides, indicating that the peri-islet BM-producing cells are not lost due to the inflammation, which has important ramifications to islet transplantation studies....

  10. 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

    2016-01-01

    . 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...

  11. 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

    1989-01-01

    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...

  12. 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

    1993-01-01

    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...

  13. ANTI-NUCLEOSOME ANTIBODIES COMPLEXED TO NUCLEOSOMAL ANTIGENS SHOW ANTI-DNA REACTIVITY AND BIND TO RAT GLOMERULAR-BASEMENT-MEMBRANE IN-VIVO

    NARCIS (Netherlands)

    KRAMERS, C; HYLKEMA, MN; VANBRUGGEN, MCJ; VANDELAGEMAAT, R; DIJKMAN, HBPM; ASSMANN, KJM; SMEENK, RJT; BERDEN, JHM; Hylkema, Machteld

    1994-01-01

    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

  14. 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

    1996-01-01

    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

  15. 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;

    1989-01-01

    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...

  16. 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

    2003-02-01

    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.

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

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    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.

  18. 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;

    1982-01-01

    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...

  19. Comparative analysis of fibrillar and basement membrane collagen expression in embryos of the sea urchin, Strongylocentrotus purpuratus.

    Science.gov (United States)

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

    1997-06-01

    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.

  20. 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.

  1. 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

    2013-01-01

    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.

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

    Science.gov (United States)

    Kuzuya, M; Kinsella, J L

    1994-11-01

    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.

  3. 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.

    Science.gov (United States)

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

    2004-06-01

    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.

  4. 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.

    Science.gov (United States)

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

    2012-05-17

    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.

  5. The basement membrane and the sex establishment in the juvenile hermaphroditism during gonadal differentiation of the Gymnocorymbus ternetzi (Teleostei: Characiformes: Characidae).

    Science.gov (United States)

    Mazzoni, Talita Sarah; Grier, Harry J; Quagio-Grassiotto, Irani

    2015-12-01

    Although there are several studies on morphogenesis in Teleostei, until now there is no research describing the role of the basement membrane in the establishment of the germinal epithelium during gonadal differentiation in Characiformes. In attempt to study these events that result in the formation of ovarian and testicular structures, gonads of Gymnocorymbus ternetzi were prepared for light microscopy. During gonadal development in G. ternetzi, all individuals first developed ovarian tissue. The undifferentiated gonad was formed by somatic cells (SC) and primordial germ cells (PGCs). After successive mitosis, the PGCs became oogonia, which entered into meiosis originating oocytes. An interstitial tissue developed. In half of the individuals, presumptive female, prefollicle cells synthesized a basement membrane around oocyte forming a follicle. Along the ventral region of the ovary, the tissue invaginated to form the ovigerous lamellae, bordered by the germinal epithelium. Stroma developed and the follicle complexes were formed. The gonadal aromatase was detected in interstitial cells in the early steps of the gonadal differentiation in both sexes. In another half of the individuals, presumptive male, there was no synthesis of basement membrane. The interstitium was invaded by numerous granulocytes. Pre-Leydig cells proliferated. Apoptotic oocytes were observed and afterward degenerated. Spermatogonia appeared near the degenerating oocytes and associated to SCs, forming testicular tubules. Germinal epithelium developed and the basement membrane was synthesized. Concomitantly, there was decrease of the gonadal aromatase and increase in the 3β-HSD enzyme expression. Thus, the testis was organized on an ovary previously developed, constituting an indirect gonochoristic differentiation. © 2015 Wiley Periodicals, Inc.

  6. Crucial Role of Mesangial Cell-derived Connective Tissue Growth Factor in a Mouse Model of Anti-Glomerular Basement Membrane Glomerulonephritis

    Science.gov (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

    2017-01-01

    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

  7. Fibrillar, fibril-associated and basement membrane collagens of the arterial wall: architecture, elasticity and remodeling under stress.

    Science.gov (United States)

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

    2015-01-01

    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.

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

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    Naoki Morimoto

    2016-01-01

    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.

  9. 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

    2015-10-01

    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.

  10. 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

    2014-09-01

    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.

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

    Science.gov (United States)

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

    2015-10-01

    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.

  12. Laminin and type IV collagen isoform substitutions occur in temporally and spatially distinct patterns in developing kidney glomerular basement membranes.

    Science.gov (United States)

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

    2013-10-01

    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.

  13. Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers.

    Science.gov (United States)

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

    2011-05-01

    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.

  14. The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome.

    Science.gov (United States)

    Wang, Haiyan; Yue, Zhihui; Wu, Jinlang; Liu, Ting; Mo, Ying; Jiang, Xiaoyun; Sun, Liangzhong

    2015-01-01

    The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria proteinuria group (proteinuria ≥50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA-VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS.

  15. 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

    2004-01-01

    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.

  16. Disease: H00582 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00582 Benign familial hematuria; Thin basement membrane nephropathy Benign familia...ildhood. The glomerular basement membrane is uniformly thin, but renal function is normal. Heterozygous muta...tions in COL4A3 or COL4A4 lead to reduced collagen network levels in the basement... Gubler MC Inherited diseases of the glomerular basement membrane. Nat Clin Pract... Nephrol 4:24-37 (2008) PMID:21071975 (gene, description) Kashtan CE, Segal Y Genetic disorders of glomerular basemen

  17. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen.

    Science.gov (United States)

    Wang, Xu-Ping; Fogo, Agnes B; Colon, Selene; Giannico, Giovanna; Abul-Ezz, Sameh R; Miner, Jeffrey H; Borza, Dorin-Bogdan

    2005-12-01

    Alport posttransplantation anti-glomerular basement membrane (GBM) nephritis is mediated by alloantibodies against the noncollagenous (NC1) domains of the alpha3alpha4alpha5(IV) collagen network, which is present in the GBM of the allograft but absent from Alport kidneys. The specificity of kidney-bound anti-GBM alloantibodies from a patient who had autosomal recessive Alport syndrome (ARAS) and developed posttransplantation nephritis was compared with that of Goodpasture autoantibodies from patients with autoimmune anti-GBM disease. Allograft-eluted alloantibodies reacted specifically with alpha3alpha4alpha5 NC1 hexamers, targeting their alpha3NC1 and alpha4NC1 subunits, and recognized a noncontiguous alloepitope formed jointly by the E(A) and E(B) regions of alpha3NC1 domain. In contrast, human Goodpasture autoantibodies recognized the separate E(A) and E(B) autoepitopes of alpha3NC1 but not the composite alloepitope. Molecular modeling of alpha3NC1 revealed that the alloepitope is more accessible within the NC1 hexamers than the partially sequestered Goodpasture autoepitopes. Overall, the specificity of alloantibodies indicated a selective lack of immune tolerance toward the alpha3 and alpha4(IV) collagen chains not expressed in patients with ARAS. Using COL4A3 knockout mice, a model of ARAS, it was shown further that acid-dissociated rather than native alpha3alpha4alpha5 NC1 hexamers elicited murine anti-GBM antibodies most closely resembling human ARAS alloantibodies. In contrast, alpha3NC1 monomers elicited Goodpasture-like murine antibodies, targeting the E(A) and E(B) autoepitopes. Thus, the identity of alpha3NC1 epitopes targeted by anti-GBM antibodies is strongly influenced by the molecular organization of the immunogen. These findings suggest that different isoforms of alpha3(IV) collagen may be implicated in the pathogenesis of ARAS posttransplantation anti-GBM nephritis and Goodpasture disease.

  18. Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus.

    Science.gov (United States)

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

    2011-10-01

    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.

  19. 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

    2001-10-04

    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

  20. 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;

    2013-01-01

    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....

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

    OpenAIRE

    Pitera JE, Scambler PJ, Woolf AS.

    2008-01-01

    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...

  2. 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

    2011-01-01

    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....

  3. β2 and γ3 laminins are critical cortical basement membrane components: ablation of Lamb2 and Lamc3 genes disrupts cortical lamination and produces dysplasia.

    Science.gov (United States)

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

    2013-03-01

    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.

  4. 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

    2005-06-01

    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.

  5. Proteolysis breaks tolerance toward intact α345(IV) collagen, eliciting novel anti-glomerular basement membrane autoantibodies specific for α345NC1 hexamers.

    Science.gov (United States)

    Olaru, Florina; Wang, Xu-Ping; Luo, Wentian; Ge, Linna; Miner, Jeffrey H; Kleinau, Sandra; Geiger, Xochiquetzal J; Wasiluk, Andrew; Heidet, Laurence; Kitching, A Richard; Borza, Dorin-Bogdan

    2013-02-15

    Goodpasture disease is an autoimmune kidney disease mediated by autoantibodies against noncollagenous domain 1 (NC1) monomers of α3(IV) collagen that bind to the glomerular basement membrane (GBM), usually causing rapidly progressive glomerulonephritis (GN). We identified a novel type of human IgG4-restricted anti-GBM autoantibodies associated with mild nonprogressive GN, which specifically targeted α345NC1 hexamers but not α3NC1 monomers. The mechanisms eliciting these anti-GBM autoantibodies were investigated in mouse models recapitulating this phenotype. Wild-type and FcγRIIB(-/-) mice immunized with autologous murine GBM NC1 hexamers produced mouse IgG1-restricted autoantibodies specific for α345NC1 hexamers, which bound to the GBM in vivo but did not cause GN. In these mice, intact collagen IV from murine GBM was not immunogenic. However, in Col4a3(-/-) Alport mice, both intact collagen IV and NC1 hexamers from murine GBM elicited IgG Abs specific for α345NC1 hexamers, which were not subclass restricted. As heterologous Ag in COL4A3-humanized mice, murine GBM NC1 hexamers elicited mouse IgG1, IgG2a, and IgG2b autoantibodies specific for α345NC1 hexamers and induced anti-GBM Ab GN. These findings indicate that tolerance toward autologous intact α345(IV) collagen is established in hosts expressing this Ag, even though autoreactive B cells specific for α345NC1 hexamers are not purged from their repertoire. Proteolysis selectively breaches this tolerance by generating autoimmunogenic α345NC1 hexamers. This provides a mechanism eliciting autoantibodies specific for α345NC1 hexamers, which are restricted to noninflammatory IgG subclasses and are nonnephritogenic. In Alport syndrome, lack of tolerance toward α345(IV) collagen promotes production of alloantibodies to α345NC1 hexamers, including proinflammatory IgG subclasses that mediate posttransplant anti-GBM nephritis.

  6. 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.

    Science.gov (United States)

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

    2016-09-01

    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.

  7. 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

    1989-01-01

    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....

  8. 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

    1993-01-01

    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...

  9. Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for α5(IV) and α2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy.

    Science.gov (United States)

    Masuda, Yukinari; Yamanaka, Nobuaki; Ishikawa, Arimi; Kataoka, Mitue; Arai, Takashi; Wakamatsu, Kyoko; Kuwahara, Naomi; Nagahama, Kiyotaka; Ichikawa, Kaori; Shimizu, Akira

    2015-06-01

    The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis. We examined the alterations of the GBM in 50 renal biopsy cases with IgA nephropathy (31.8 ± 17.6 years old) using double immunostaining for the α2(IV) and α5(IV) chains of type IV collagen, and examining the ultrastructural alterations by transmission electron microscopy (TEM) and low-vacuum scanning electron microscopy (LV-SEM). The GBM of IgA nephropathy cases showed various morphological and qualitative alterations. In the TEM findings, thinning, gaps, rupture, thickening with a lamellar and reticular structure and double contours were detected in the GBM. Double immunostaining for α5(IV) and α2(IV) showed thickening of the GBM with reduced α5(IV) and increased α2(IV), or mosaic images of α5(IV) and α2(IV), and holes, fractures, spiny projections and rupture of α5(IV) in the GBM. In addition, LV-SEM showed an etched image and multiple holes in a widening and wavy GBM. These findings might be associated with the development of a brittle GBM in IgA nephropathy. Glomerular basement membrane alterations were frequently noted in IgA nephropathy, and were easily evaluated by double immunostaining for α2(IV) and α5(IV) of type IV collagen and LV-SEM. The application of these analyses to human renal biopsy specimens may enhance our understanding of the alterations of the GBM that occur in human glomerular diseases.

  10. 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.

    1998-09-30

    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.

  11. 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

    2008-01-01

    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.

  12. [Monoclonal autoantibodies to the epithelial basement membrane cells of human skin and thymus obtained through immunization with Rickettsia prowazekii antigens].

    Science.gov (United States)

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

    1989-05-01

    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.

  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. 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

  15. [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].

    Science.gov (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

    1998-11-01

    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.

  16. 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)

    2016-01-01

    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。

  17. 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.

    1988-10-01

    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.

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

    Science.gov (United States)

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

    2016-08-01

    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.

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

    Science.gov (United States)

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

    2008-12-15

    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.

  20. Goodpasture syndrome. Localization of the epitope for the autoantibodies to the carboxyl-terminal region of the alpha 3(IV) chain of basement membrane collagen.

    Science.gov (United States)

    Kalluri, R; Gunwar, S; Reeders, S T; Morrison, K C; Mariyama, M; Ebner, K E; Noelken, M E; Hudson, B G

    1991-12-15

    The autoantibodies of patients with Goodpasture syndrome are primarily targeted to the noncollagenous (NC1) domain of the alpha 3(IV) chain of basement membrane collagen (Saus, J., Wieslander, J., Langeveld, J. P. M., Quinones, S., and Hudson, B. G. (1988) J. Biol. Chem. 263, 13374-13380). In the present study, the location of the Goodpasture epitope in human alpha 3NC1 was determined, and its structure was partially characterized. This was achieved by identification of regions of alpha 3NC1 which are candidates for the epitope and which are structurally unique among the five known homologous NC1 domains (alpha 1-alpha 5); amino acids that are critical for Goodpasture antibody binding, by selective chemical modifications; and regions that are critical for Goodpasture antibody binding, by synthesis of 12 alpha 3NC1 peptides and measurement of their antibody binding capacity. The carboxyl-terminal region, residues 198-233, was identified as the most likely region for the epitope. By experiment, lysine and cysteine were identified as critical amino acids for antibody binding. Three synthetic peptides were found to inhibit Goodpasture antibody binding to alpha 3NC1 markedly: a 36-mer (residues 198-233), a 12-mer (residues 222-233), and a 5-mer (residues 229-233). Together, these results strongly indicate that the Goodpasture epitope is localized to the carboxyl-terminal region of alpha 3NC1, encompassing residues 198-233 as the primary antibody interaction site and that its structure is discontinuous. These findings provide a conceptual framework for future studies to elucidate a more complete epitope structure by sequential replacement of residues encompassing the epitope using cDNA expression products and peptides synthesized chemically.

  1. [Goodpasture's disease or syndrome? Apropos of a case].

    Science.gov (United States)

    Berti, F; Carnabuci, A; Onetti, A; Polchi, S; Sorrentino, R

    1997-01-01

    Goodpasture's disease is characterized by lung haemorrhage, associated with glomerulus basement membrane antibody glomerulonephritis, and circulating basement membrane antibody. Other diseases (Wegener, LES, arteritis) may have the same kidney and lung involvement. The Authors present a clinical case of rapidly progressive renal failure where renal biopsy showed an extensive extracapillary proliferative glomerulonephritis with linear deposits of antibody in the basement membrane, similar to Goodpasture's disease, with following lung involvement, but without hemoptysis and in absence of circulating antiglomerular basement membrane antibody. The Authors think it could be a case of Goodpasture's disease, even if it did not show the above-mentioned symptoms, whether out of the characteristic clinical course or the exclusion of all the other diseases. The Authors believe that the absence of circulating basement membrane antibody could be due to their sediment in the target organs and suggest a revision of the standards required for the Goodpasture's disease diagnosis.

  2. 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

    1994-05-01

    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

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

    Science.gov (United States)

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

    2000-02-01

    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

  4. Idiopathic membranous nephropathy: an autoimmune disease.

    Science.gov (United States)

    Makker, Sudesh P; Tramontano, Alfonso

    2011-07-01

    For more than 50 years researchers have debated the evidence for an autoimmune basis of human idiopathic membranous nephritis (MN). Work published in the past 2 years has substantially strengthened the belief that MN is indeed an autoimmune disease of the kidney. Autoantibodies of the IgG4 subclass to at least three podocyte membrane proteins including phospholipase A(2)-receptor, aldose reductase, and manganese superoxide dismutase have been detected by immunoblotting in sera as well as in acid eluates prepared from renal biopsy tissue of patients with this disease, using either whole tissue or microdissected glomeruli from frozen sections. In each case the podocyte antigen has been shown to co-localize with the subepithelial glomerular immune deposits in renal tissue of the same patients. It is not certain if any of these podocyte proteins is an inciting/primary autoantigen or whether they are secondary antigens recruited by intermolecular epitope-spreading, initiating from a yet-to-be-discovered autoantigen. Although it is clear that autoantibodies to podocyte membrane proteins are elicited in idiopathic MN and contribute to the formation of the subepithelial deposits, many questions remain concerning the triggers for their development and their contribution toward proteinuria and progression of the disease.

  5. Membranous glomerulopathy and massive cervical lymphadenopathy due to immunoglobulin G4-disease

    Directory of Open Access Journals (Sweden)

    Kamel El-Reshaid

    2017-01-01

    Full Text Available A 32-year-old male presented with acute and severe nephrotic syndrome as well as massive right cervical lymphadenopathy for <2 years. Computed tomography scan of the chest, abdomen, and pelvis did not reveal any lymphadenopathy. Histopathology and immunohistochemical testing of his lymph node biopsy showed infiltrate enriched with immunoglobulin G4 (IgG4-positive plasma cells. His kidney biopsy showed granular membranous deposits of IgG4 in the basement membrane without interstitial infiltrate. Antiphospholipid 2 receptor antibodies were absent excluding its "idiopathic" nature. Since he was allergic to rituximab, he was treated with corticosteroids for two months and a combination of tacrolimus and mycophenolate. His lymphadenopathy disappeared, and his proteinuria abated. The dose of the latter two medications was reduced to half after four months and will be maintained for a minimum of two years to prevent relapse of his disease.

  6. 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

    2012-01-01

    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.

  7. Seismic basement in Poland

    Science.gov (United States)

    Grad, Marek; Polkowski, Marcin

    2016-06-01

    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.

  8. [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].

    Science.gov (United States)

    Dirnhofer, R; Sonnabend, W; Sigrist, T

    1978-05-20

    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.

  9. 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.

    Science.gov (United States)

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

    1987-08-01

    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.

  10. Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

    OpenAIRE

    Cowling, Belinda S; Anne Toussaint; Jean Muller; Jocelyn Laporte

    2012-01-01

    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Too...

  11. Fatty acids, membrane viscosity, serotonin and ischemic heart disease

    OpenAIRE

    Cocchi Massimo; Tonello Lucio; Lercker Giovanni

    2010-01-01

    Abstract Novel markers for ischemic heart disease are under investigation by the scientific community at international level. This work focuses on a specific platelet membrane fatty acid condition of viscosity which is linked to molecular aspects such as serotonin and G proteins, factors involved in vascular biology. A suggestive hypothesis is considered about the possibility to use platelet membrane viscosity, in relation to serotonin or, indirectly, the fatty acid profile, as indicator of i...

  12. Poliomyelitis in MuLV-Infected ICR-SCID Mice after Injection of Basement Membrane Matrix Contaminated with Lactate Dehydrogenase-Elevating Virus

    OpenAIRE

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

    2011-01-01

    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 Fv1n 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 si...

  13. Evidence for a membrane defect in Alzheimer disease brain

    Science.gov (United States)

    Nitsch, R. M.; Blusztajn, J. K.; Pittas, A. G.; Slack, B. E.; Growdon, J. H.; Wurtman, R. J.

    1992-01-01

    To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.

  14. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

    Institute of Scientific and Technical Information of China (English)

    Konstantinos Dean BOUDOULAS; Peter J MOHLER

    2011-01-01

    Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects ("channelopathies" - the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2),ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAPg), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease.

  15. Eosinophil localization to the basement membrane zone is autoantibody- and complement-dependent in a human cryosection model of bullous pemphigoid.

    Science.gov (United States)

    Messingham, Kelly N; Wang, Jeffrey W; Holahan, Heather M; Srikantha, Rupasree; Aust, Samantha C; Fairley, Janet A

    2016-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by antibodies (IgG and IgE) targeting cell-substrate adhesion proteins. A variety of BP models suggest that autoantibody-dependent neutrophil degranulation is essential for blister formation. However, lesional biopsies reveal a predominance of eosinophils and few neutrophils. Our goal was to evaluate the role of antibodies and complement in eosinophil localization, degranulation and split formation at the dermo-epidermal junction (DEJ) utilizing a human skin cryosection model of BP paired with a human eosinophilic cell line, 15HL-60. Expression of receptors for IgG (FcγRII), IgE (FcεRI) and complement (CR1 and CR3) was confirmed on 15HL-60 cells using flow cytometry. 15HL-60 expression of granule protein [eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO)] mRNA and their degranulation in vitro was confirmed using RT-PCR and ELISA, respectively. For cryosection experiments, BP or control sera or IgG and IgE antibodies purified from BP sera were utilized in combination with 15HL-60 cells ± fresh complement. Both BP serum and fresh complement were required for localization of 15-HL60 cells to the DEJ. Interestingly, eosinophil localization to the DEJ was dependent on IgG, but not IgE, and complement. However, no subepidermal split was observed. Additionally, the 15HL-60 cells did not degranulate under any experimental conditions and direct application of cell lysate to cryosections did not result in a split. Our observation that eosinophil localization to the DEJ is dependent on IgG mediated complement fixation provides additional insight into the sequence of events during the development of BP lesions.

  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

    2008-01-01

    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. Hereditary skin diseases of hemidesmosomes

    NARCIS (Netherlands)

    Jonkman, MF

    1999-01-01

    Studies of hereditary blistering skin diseases (epidermolysis bullosa) and targeted gene mutation experiments in knockout mice have greatly improved our understanding of hemidesmosomes and their associated structures in the cytoskeleton and basement membrane of the skin and mucous membranes. At leas

  18. Enfermedad de la mucosa oral: Penfigoide de las membranas mucosas Oral mucosal disease: Mucouse membrane pemphigoid

    Directory of Open Access Journals (Sweden)

    N. Discepoli

    2009-04-01

    Full Text Available Los trastornos vesículobullosos subepiteliales representan desordenes autoinmunitarios que cogen origen de reacciones dirigidas hacia componentes de los hemidesmosomas o bien de las Zonas de la Membrana Basal (ZMB de los epitelios escamosos estratificados. A estos trastornos ha sido conferidoel término de enfermedades ampollosa subepiteliales inmunomediadas (EASIM y el penfigoide de las membranas mucosas (PMM es el más frecuente. Todas las enfermedades subepiteliales vesiculobullosas se presentan como lesiones ampollosas y descamativas, y el diagnostico debe de ser confirmado por una biopsia junta a tinción inmunológica. No hay un único tratamiento capaz de controlar todas las enfermedades subepiteliales vesiculoampollosas; las diferencias inmunológicas entre las EASIM proporciona diferencias en las respuestas al tratamiento. Hoy en día el tratamiento inmunorregulador es usado para controlar la lesión oral de PMM.Subepithelial vesiculobullous conditions are chronic autoimmune disorders that arise from reactions directed against components of the hemidesmosomes or basement membrane zones (BMZ of stratified squamous epithelium to which the term immune-mediated subepithelial blistering diseases (IMSEBD has been given. Mucous membrane pemphigoid (MMP is the most common, but variants do exist. All subepithelial vesiculobullous disorders present as blisters and erosions, and diagnosis must be confirmed by biopsy examination with immunostaining, sometimes supplemented by other investigations. No single treatment reliably controls all subepithelial vesiculobullous disorders; the immunological differences within IMSEBD may account for differences in responses to treatment. Currently, as well as improving oral hygiene, immunomodulatory treatment is used to control the oral lesions of MMP, but it is not known if its specific subsets reliably respond to different agents.

  19. Epiretinal membrane removal in patients with Stargardt disease

    Directory of Open Access Journals (Sweden)

    Muna Bhende

    2015-01-01

    Full Text Available Epiretinal membranes (ERMs in Stargardt disease have been known to undergo spontaneous separation in children. Results of surgical intervention in adult patients with Stargardt disease have rarely been reported. A retrospective review of results of surgical intervention for ERM causing visual impairment in two adult patients of Stargardt disease was carried out. Both patients developed ERM in one eye during their follow-up period with the resultant drop in their preexisting visual acuity. Postsurgery, restoration of foveal contour with some improvement in visual acuity was observed in both patients. No adverse effect of surgery was noted.

  20. Effects of chronic kidney disease on blood cells membrane properties.

    Science.gov (United States)

    Kaderjakova, Z; Lajdova, I; Horvathova, M; Morvova, M; Sikurova, L

    2012-10-01

    Chronic kidney disease (CKD) is progressive loss of renal function associated among others with increased intracellular calcium concentration. The purpose of this study was to identify the effects of CKD on cell membrane properties such as human red blood cell Ca(2+) ATPase activity, lymphocyte plasma membrane P2X(7) receptor expression and function. This could help us in elucidating the origin of increased calcium concentration in blood cells. We found out Ca(2+) ATPase activity is decreased in early stage CKD patients resulting in altered calcium removal from cytoplasm. By means of flow cytometry we assessed that P2X(7) receptor expression on lymphocyte membrane is 1.5 fold increased for CKD patients. Moreover, we detected an increased uptake of ethidium bromide through this receptor in CKD at basal conditions. It means CKD lymphocyte membranes contain more receptors which are more permeable thus allowing increased calcium influx from extracellular milieu. Finally, we can state alterations in blood cell membranes are closely linked to CKD and may be responsible for intracellular calcium accumulation.

  1. Measure Guideline: Basement Insulation Basics

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-01

    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.

  2. basement reservoir geometry and properties

    Science.gov (United States)

    Walter, bastien; Geraud, yves; Diraison, marc

    2017-04-01

    Basement reservoirs are nowadays frequently investigated for deep-seated fluid resources (e.g. geothermal energy, groundwater, hydrocarbons). The term 'basement' generally refers to crystalline and metamorphic formations, where matrix porosity is negligible in fresh basement rocks. Geothermal production of such unconventional reservoirs is controlled by brittle structures and altered rock matrix, resulting of a combination of different tectonic, hydrothermal or weathering phenomena. This work aims to characterize the petro-structural and petrophysical properties of two basement surface analogue case studies in geological extensive setting (the Albert Lake rift in Uganda; the Ifni proximal margin of the South West Morocco Atlantic coast). Different datasets, using field structural study, geophysical acquisition and laboratory petrophysical measurements, were integrated to describe the multi-scale geometry of the porous network of such fractured and weathered basement formations. This study points out the multi-scale distribution of all the features constituting the reservoir, over ten orders of magnitude from the pluri-kilometric scale of the major tectonics structures to the infra-millimetric scale of the secondary micro-porosity of fractured and weathered basements units. Major fault zones, with relatively thick and impermeable fault core structures, control the 'compartmentalization' of the reservoir by dividing it into several structural blocks. The analysis of these fault zones highlights the necessity for the basement reservoirs to be characterized by a highly connected fault and fracture system, where structure intersections represent the main fluid drainage areas between and within the reservoir's structural blocks. The suitable fluid storage areas in these reservoirs correspond to the damage zone of all the fault structures developed during the tectonic evolution of the basement and the weathered units of the basement roof developed during pre

  3. OUTCOME OF VENTILATION IN HYALINE MEMBRANE DISEASE: THE INDIAN EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Nayana Prabha

    2016-06-01

    Full Text Available OBJECTIVE To study the short-term outcome of both preterm and term babies requiring assisted ventilation for hyaline membrane disease and report the complications contributing to morbidity and mortality of these patients from a regional medical college with limited resources. DESIGN Retrospective file review. SETTING Regional Medical College. PARTICIPANTS All babies ventilated for HMD over a 6-year period from June 2008 to June 2014. OUTCOME MEASURES Outcome of ventilation and factors contributing to mortality. RESULTS Out of 100 babies with hyaline membrane disease who were ventilated, 82% survived. Increasing gestational age and birth weight was associated with survival. The commonest complication was shock (77% and the commonest cause of mortality was septicaemia (77%. Septicaemia, Disseminated Intravascular Coagulation (DIC and pulmonary haemorrhage were significantly more common complications babies who died (p<0.05. Binary logistic regression analysis showed that DIC (Odds ratio 5.2 [Confidence intervals (C.I. 1.1-27.1] and pulmonary haemorrhage (OR 18 [1.72-45.2] to be predictors of mortality. The incidence of intraventricular haemorrhage was 1% and that of pneumothorax was 2%. The initial peak inspiratory pressure administered was significantly lower (p=0.033 and maximum peak end expiratory pressure was significantly higher in those who expired (p=0.027. CONCLUSION Outcome of ventilation for hyaline membrane disease improves with increasing gestational age and birth weight. The commonest cause of mortality and morbidity were septicaemia and shock respectively.

  4. Viruses in the Oceanic Basement.

    Science.gov (United States)

    Nigro, Olivia D; Jungbluth, Sean P; Lin, Huei-Ting; Hsieh, Chih-Chiang; Miranda, Jaclyn A; Schvarcz, Christopher R; Rappé, Michael S; Steward, Grieg F

    2017-03-07

    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 × 10(5) to 2 × 10(5) 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.IMPORTANCE The hydrothermally active ocean basement is voluminous and likely provided conditions critical to the origins of life, but the microbiology of this vast habitat is not

  5. Defective membrane remodeling in neuromuscular diseases: insights from animal models.

    Directory of Open Access Journals (Sweden)

    Belinda S Cowling

    Full Text Available Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1, and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1 a common molecular pathway underlying these different neuromuscular diseases, and (2 tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.

  6. An 80-year-old female with double positive disease: Case report and brief review of literature.

    Science.gov (United States)

    Almouradi, Tarek; Hart, Peter; Muram-Zborovski, Talia

    2013-01-01

    Goodpasture's syndrome is a triad of alveolar hemorrhage, Glomerulonephritis and circulating anti Glomerular basement membrane antibodies, 25% of cases test positive for ANCA antibodies, this association is known as Double positive disease. This article describes a rare presentation of this entity and reviews available literature. 80 year old female presented with hemoptysis and renal failure, she tested positive for both p ANCA and anti glomerular basement membrane antibodies, and despite aggressive medical treatment, she suffered a frustrating outcome. Double positive disease accounts for 25% of cases of Goodpasture's syndrome, a suggested Pathophysiology of this association is the renal involvement in ANCA Vasculitis leading to the exposure of antigens from the basement membrane and the formation of antibodies. This entity is believed to carry better prognosis when compared to isolated anti glomerular basement membrane disease.

  7. Differential expression of laminin isoforms in diabetic nephropathy and other renal diseases.

    Science.gov (United States)

    Setty, Suman; Michael, Alfred A; Fish, Alfred J; Michael Mauer, S; Butkowski, Ralph J; Virtanen, Ismo; Kim, Youngki

    2012-06-01

    Laminin a non-collagenous glycoprotein is a major component of the renal glomerular basement membrane and mesangium. Thus far eleven distinct chains have been described, permutations of which make up 15 laminin isoforms. Laminin molecules interact with cells and other matrix molecules during organ development and differentiation. We studied the distribution of laminin isoforms in patients with type 1 diabetic nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis and IgA nephropathy/ Henoch-Schönlein purpura. Immunofluorescence microscopic studies with laminin-chain-specific antibodies to the α1, α2, α5, β1, β2 and γ1 chains detected α2, β1 and γ1 chain expression in the normal mesangium and α5, β2 and γ1 in normal glomerular basement membrane. Significantly, constituents of the glomerular basement membrane, α5, β2 and γ1 chains were overexpressed in kidneys with diabetic nephropathy. Initially the constituents of the mesangium increased commensurate with the degree of mesangial expansion and degree of diabetic nephropathy. Reduction in α2 chain intensity was observed with severe mesangial expansion and in the areas of nodular glomerulosclerosis. In addition, with late disease aberrant expression of α2 and β2 chains was observed in the mesangium. Glomerular basement membrane in renal disease overexpressed molecules normally present in that location. In summary, the alterations in basement membrane composition in various renal diseases seem to not only reflect the balance between synthesis and degradation of normal basement membrane constituents, but also their aberrant expression.

  8. Viruses in the Oceanic Basement

    Science.gov (United States)

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

    2017-01-01

    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

  9. 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

    2010-01-01

    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.

  10. 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

    2008-01-01

    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

  11. Membranous nephropathy PLA2R+ associated with Chagas disease.

    Science.gov (United States)

    Xavier-Júnior, José Cândido Caldeira; Silva, Vanessa Dos Santos; Viero, Rosa Marlene

    2015-01-01

    Chagas disease (CD) - a tropical parasitic disease caused by the protozoan Trypanosoma cruzi - is a major health problem in Latin America. The immune response against the parasite is responsible for chronic CD lesions. Currently, there are no reports of an association between CD and membranous nephropathy (MN). The detection of the phospholipase A2 receptor (PLA2R) as a target antigen in idiopathic MN can improve the differential diagnosis of primary and secondary forms of MN. The authors report the case of a male patient with positive serology for CD who presented sudden death and underwent autopsy. Histological sections of the heart showed multifocal inflammatory infiltrate composed mainly of mononuclear cells, leading to myocardiocytes necrosis and interstitial fibrosis. The kidneys showed a MN with positive expression for PLA2R. As far as we know, this is the first report of a case of primary MN in a patient with CD, with severe chronic cardiomyopathy and heart failure.

  12. 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

    2016-01-01

    ) Mutations in COL4A5 gene were detected.Mann-Whitney test and x2 test were used.Result Totally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative.The two groups of patients were compared, the median age at analysis was 11.0 vs.7.2 years (Z =-1.839, P =0.066), the 24-hour urine protein was 1.50 vs.0.57 g/d (Z =-1.212, P =0.226), the rate of hearing loss was 28% vs.53% (x2 =3.619, P =0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs.12 (x2 =2.377,P =0.128), the median age of ESRD was 31.0 vs.16.6 years (Z =-2.554, P =0.011), the rate of missense mutations in COL4A5 gene was 67% vs.52% (x2 =1.424, P =0.313).Conclusion Compared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene.But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.

  13. Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease

    Science.gov (United States)

    Dauvergne, Maxime; Moktefi, Anissa; Rabant, Marion; Vigneau, Cécile; Kofman, Tomek; Burtey, Stephane; Corpechot, Christophe; Stehlé, Thomas; Desvaux, Dominique; Rioux-Leclercq, Nathalie; Rouvier, Philippe; Knebelmann, Bertrand; Boffa, Jean-Jacques; Frouget, Thierry; Daugas, Eric; Jablonski, Mathieu; Dahan, Karine; Brocheriou, Isabelle; Remy, Philippe; Grimbert, Philippe; Lang, Philippe; Chazouilleres, Oliver; Sahali, Dil; Audard, Vincent

    2015-01-01

    Abstract The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined. We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens. The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating. Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN. PMID:26222864

  14. Hyaline membrane disease (HMD: the role of the perinatal pathologist

    Directory of Open Access Journals (Sweden)

    Giorgia Locci

    2014-06-01

    Full Text Available Hyaline membrane disease (HMD, the pathologic correlate of respiratory distress syndrome (RDS of the newborn, is an acute lung disease of premature infant caused by inadequate amounts of surfactant. Decreased surfactant results in insufficient surface tension in the alveolus during expiration, leading to atelectasis, decreased gas exchange, severe hypoxia and acidosis. HMD predominantly occurs in infants younger than 32 weeks of gestation and weighing less than 1,200 g. In the interpretation of perinatal lung pathology, it is necessary to consider the development of the immature lung, particulary in the third trimester. Microscopically HMD is characterized by the occurrence of dilated terminal and respiratory bronchioles and of alveolar ducts lined by acellular eosinophilic hyaline membranes. The membranes are composed of necrotic alveolar lining cells, amniotic fluid constituents and fibrin. Retinopathy of prematurity and bronchopulmonary dysplasia are late complications of RDS that usually occur in infants who weigh less than 1,500 g and were maintained on a mechanical respiration more than 6 days. Here a pratical approach to a microscopic analysis of the lung in newborns died with the clinical setting of RDS is presented. The most important pathological findings for a complete clinical pathological diagnosis are: the evaluation of the architectural lung development; the endothelial cell lesions; the interstitial edema; the occurrence of disseminated intravascular coagulation; the presence of associated inflammatory lesions. The usefulness of some immunohistochemical stains is also underlined, including anti-surfactant, anti-smooth muscle actin and anti-CD31 to better evaluate surfactant production, pulmonary artery maturation and endothelial cell damage, respectively. Finally, the prevalent role of endothelial dysfunction and endothelial barrier loss is underlined, representing a major pathological event in the deposition of HMD

  15. 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

    2015-01-01

    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

  16. A case of subepidermal blistering disease with autoantibodies to multiple laminin subunits who developed later autoantibodies to alpha-5 chain of type IV collagen associated with membranous glomerulonephropathy.

    Science.gov (United States)

    Sueki, Hirohiko; Sato, Yoshinori; Ohtoshi, Shinpei; Nakada, Tokio; Yoshimura, Ashio; Tateishi, Chiharu; Borza, Dorin-Bogdan; Fader, William; Ghohestani, Reza F; Hirako, Yoshiaki; Koga, Hiroshi; Ishii, Norito; Tsuchisaka, Atsunari; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi

    2015-09-01

    We report a 68-year-old Japanese female patient with subepidermal blistering disease with autoantibodies to multiple laminins, who subsequently developed membranous glomerulonephropathy. At skin disease stage, immunofluorescence demonstrated IgG anti-basement membrane zone antibodies reactive with dermal side of NaCl-split skin. Immunoblotting of human dermal extract, purified laminin-332, hemidesmosome-rich fraction and laminin-521 trimer recombinant protein (RP) detected laminin γ-1 and α-3 and γ-2 subunits of laminin-332. Three years after skin lesions disappeared, nephrotic symptoms developed. Antibodies to α-3 chain of type IV collagen (COL4A3) were negative, thus excluding the diagnosis of Goodpasture syndrome. All anti-laminin antibodies disappeared. Additional IB and ELISA studies of RPs of various COL4 chains revealed reactivity with COL4A5, but not with COL4A6 or COL4A3. Although diagnosis of anti-laminin γ-1 (p200) pemphigoid or anti-laminin-332-type mucous membrane pemphigoid could not be made, this case was similar to previous cases with autoantibodies to COL4A5 and/or COL4A6.

  17. [An autopsy case of Goodpasture syndrome preceded with membranous glomerulonephritis].

    Science.gov (United States)

    Takeuchi, K; Takeda, T; Sakai, I; Taneichi, K; Shibaki, H

    1997-12-01

    Goodpasture syndrome (GS) is an autoimmune disorder characterized by the association of pulmonary hemorrhage and rapidly progressive glomerulonephritis. The pathogenesis of GS is still unknown, but was shown to be the result that antibodies directed against glomerular basement membrane (GBM) antigens could injure both glomerular and pulmonary alveolar basement membrane. And membranous glomerulonephritis (MGN) is a glomerular disease characterized by epimembranous immune deposits and basement membrane thickening. MGN typically presents with the onset of nephrotic syndrome, but it often presents with only asymptomatic proteinuria. We reported an autopsy case of GS preceded with MGN. A 70-year-old man was admitted to our hospital with acute renal failure in May 2, 1996. Percutaneous renal biopsy demonstrated a crescentic glomerulonephritis associated with MGN and linear immunofluorescent staining of the basement membrane with antibodies to IgG. Two weeks later on admission he began to develop slight hemoptysis and chest X-ray showed pulmonary hemorrhage, Furthermore, his serum anti-GBM antibodies titer was very high. He was diagnosed as GS associated with MGN and treated with plasma exchange, glucocorticoid, and cyclophosphamide. Though his symptom was improved for intensive support, he suddenly died on June 22. Autopsied lungs showed focal pulmonary hemorrhage, but were not considered to be life-threatening. The cause of the death remained unclear.

  18. Disease: H00877 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available basement-membrane integrity and cerebral small-vessel disease. The COL4A1 stroke syndrome. Curr Med Chem 17:...COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. Ann Neurol 62:177-84 (2007) ...

  19. Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome.

    Science.gov (United States)

    Kalluri, R; Wilson, C B; Weber, M; Gunwar, S; Chonko, A M; Neilson, E G; Hudson, B G

    1995-10-01

    Antiglomerular basement membrane (GBM) antibodies can cause glomerulonephritis or pulmonary hemorrhage by themselves or Goodpasture syndrome when they occur together. It is unknown if variations in antibody reactivity contribute to the different patterns of organ involvement seen in this disease. This study examines the reactivity of the alpha 1-alpha 6 NC1 domains of Type IV collagen, the putative autoantigen, in sera from patients with anti-GBM antibodies after various clinical presentations of lung hemorrhage and renal injury. Serum or plasma containing anti-GBM antibodies from 35 patients with combined glomerulonephritis and pulmonary hemorrhage, 19 with glomerulonephritis alone, and 4 with pulmonary hemorrhage alone were compared with samples from 19 normal controls and 32 patients with other kidney diseases. Four different immunologic assays were performed with bovine alpha 1-alpha 6(IV) and recombinant human type alpha 1-alpha 5(IV) collagen NC1 domains. The study found that the anti-GBM antibodies from all patients reacted with the alpha 3(IV) NC1 (85% exclusively). Additional limited reactivity with the alpha 1(IV) NC1 and alpha 4(IV) NC1 was found in 15 and 3%, respectively. This non-alpha 3(IV) NC1 reactivity was most frequent in the patients with anti-GBM antibodies and glomerulonephritis alone. None of the patients had reactivity to other basement membrane components like laminin, fibronectin, heparan sulfate proteoglycan, entactin, or the 7S and triple helical fragments of Type IV collagen. The observed alpha-chain NC1 reactivity was confined to patients with anti-GBM antibodies with no additional reactivities detected among a large number of other kidney diseases controls. The correlation of alpha 1-alpha 6(IV) NC1 reactivity in a large number of patients with anti-GBM antibodies defined by classic assays definitively establishes that reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary for the expression of autoimmune disease

  20. Membraner

    DEFF Research Database (Denmark)

    Bach, Finn

    2009-01-01

    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...

  1. Detection of Membrane Fluidity in Submitochondrial Particles of Platelets and Erythrocyte Membranes from Mexican Patients with Alzheimer Disease by Intramolecular Excimer Formation of 1,3 Dipyrenylpropane

    Directory of Open Access Journals (Sweden)

    G.G. Ortiz

    2008-01-01

    Full Text Available It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes.

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

    Directory of Open Access Journals (Sweden)

    Chia-Chao Wu

    2011-01-01

    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. Structural elucidation of the interaction between neurodegenerative disease-related tau protein with model lipid membranes

    Science.gov (United States)

    Jones, Emmalee M.

    A protein's sequence of amino acids determines how it folds. That folded structure is linked to protein function, and misfolding to dysfunction. Protein misfolding and aggregation into beta-sheet rich fibrillar aggregates is connected with over 20 neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized in part by misfolding, aggregation and deposition of the microtubule associated tau protein into neurofibrillary tangles (NFTs). However, two questions remain: What is tau's fibrillization mechanism, and what is tau's cytotoxicity mechanism? Tau is prone to heterogeneous interactions, including with lipid membranes. Lipids have been found in NFTs, anionic lipid vesicles induced aggregation of the microtubule binding domain of tau, and other protein aggregates induced ion permeability in cells. This evidence prompted our investigation of tau's interaction with model lipid membranes to elucidate the structural perturbations those interactions induced in tau protein and in the membrane. We show that although tau is highly charged and soluble, it is highly surface active and preferentially interacts with anionic membranes. To resolve molecular-scale structural details of tau and model membranes, we utilized X-ray and neutron scattering techniques. X-ray reflectivity indicated tau aggregated at air/water and anionic lipid membrane interfaces and penetrated into membranes. More significantly, membrane interfaces induced tau protein to partially adopt a more compact conformation with density similar to folded protein and ordered structure characteristic of beta-sheet formation. This suggests possible membrane-based mechanisms of tau aggregation. Membrane morphological changes were seen using fluorescence microscopy, and X-ray scattering techniques showed tau completely disrupts anionic membranes, suggesting an aggregate-based cytotoxicity mechanism. Further investigation of protein constructs and a "hyperphosphorylation" disease mimic helped

  4. Linear IgA disease: clinical presentation, diagnosis, and pathogenesis.

    Science.gov (United States)

    Venning, Vanessa A

    2012-05-01

    Linear IgA disease is one of the rarer subepidermal blistering diseases. Linear IgA disease is a chronic, acquired, autoimmune blistering disease that is characterized by subepidermal blistering and linear deposition of IgA basement membrane antibodies. The disease affects both children and adults and, although there are some differences in their clinical presentations, there is considerable overlap with shared immunopathology and immunogenetics. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Autophagocytosis of the apical membrane in microvillus inclusion disease

    OpenAIRE

    Reinshagen, K; Naim, H. Y.; Zimmer, K-P

    2002-01-01

    Backgrounds: Microvillus inclusion disease (MID) is a disorder with the clinical signs of intractable diarrhoea in the newborn and infancy. The typical pathological features of the disease are well known whereas the pathophysiology is still unclear.

  6. Common Membrane Trafficking Defects of Disease Associated Dynamin 2 Mutations

    OpenAIRE

    Liu, Ya-Wen; Lukiyanchuk, Vasyl; Schmid, Sandra L.

    2011-01-01

    Dynamin (Dyn) is a multidomain and multifunctional GTPase best known for its essential role in clathrin-mediated endocytosis (CME). Dyn2 mutations have been linked to two human diseases, Centronuclear Myopathy (CNM) and Charcot-Marie-Tooth (CMT) disease. Paradoxically, although Dyn2 is ubiquitously expressed and essential for embryonic development, the disease-associated Dyn2 mutants are autosomal dominant, but result in slowly progressing and tissue-specific diseases. Thus, although the cell...

  7. Erythrocyte membrane stability to hydrogen peroxide is decreased in Alzheimer disease.

    Science.gov (United States)

    Gilca, Marilena; Lixandru, Daniela; Gaman, Laura; Vîrgolici, Bogdana; Atanasiu, Valeriu; Stoian, Irina

    2014-01-01

    The brain and erythrocytes have similar susceptibility toward free radicals. Therefore, erythrocyte abnormalities might indicate the progression of the oxidative damage in Alzheimer disease (AD). The aim of this study was to investigate erythrocyte membrane stability and plasma antioxidant status in AD. Fasting blood samples (from 17 patients with AD and 14 healthy controls) were obtained and erythrocyte membrane stability against hydrogen peroxide and 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH), serum Trolox equivalent antioxidant capacity (TEAC), residual antioxidant activity or gap (GAP), erythrocyte catalase activity (CAT), erythrocyte superoxide dismutase (SOD) activity, erythrocyte nonproteic thiols, and total plasma thiols were determined. A significant decrease in erythrocyte membrane stability to hydrogen peroxide was found in AD patients when compared with controls (Perythrocyte membrane stability to hydrogen peroxide. Reduced erythrocyte membrane stability may be further evaluated as a potential peripheral marker for oxidative damage in AD.

  8. Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases

    OpenAIRE

    Fantini, Jacques; Yahi, Nouara

    2010-01-01

    Alzheimer, Parkinson and other neurodegenerative diseases involve a series of brain proteins, referred to as ‘amyloidogenic proteins’, with exceptional conformational plasticity and a high propensity for self-aggregation. Although the mechanisms by which amyloidogenic proteins kill neural cells are not fully understood, a common feature is the concentration of unstructured amyloidogenic monomers on bidimensional membrane lattices. Membrane-bound monomers undergo a series of lipid-dependent co...

  9. Fibulins and Their Role in Cardiovascular Biology and Disease

    DEFF Research Database (Denmark)

    Cangemi, Claudia; Hansen, Maria Lyck; Argraves, William Scott

    2014-01-01

    Fibulins are a group of extracellular matrix proteins of which many are present in high amounts in the cardiovascular system. They share common biochemical properties and are often found in relation to basement membranes or elastic fibers. Observations in humans with specific mutations in fibulin...... as a cardiovascular disease marker....

  10. Changes in the plasma membrane in metabolic disease: impact of the membrane environment on G protein-coupled receptor structure and function.

    Science.gov (United States)

    Desai, Aditya J; Miller, Laurence J

    2017-07-10

    Drug development targeting GPCRs often utilizes model heterologous cell expression systems, reflecting an implicit assumption that the membrane environment has little functional impact on these receptors or on their responsiveness to drugs. However, much recent data have illustrated that membrane components can have an important functional impact on intrinsic membrane proteins. This review is directed toward gaining a better understanding of the structure of the plasma membrane in health and disease, and how this organelle can influence GPCR structure, function and regulation. It is important to recognize that the membrane provides a potential mode of lateral allosteric regulation of GPCRs and can affect the effectiveness of drugs and their biological responses in various disease states, which can even vary among individuals across the population. The type 1 cholecystokinin receptor is reviewed as an exemplar of a class A GPCR that is affected in this way by changes in the plasma membrane. © 2017 The British Pharmacological Society.

  11. Deoxygenation affects tyrosine phosphoproteome of red cell membrane from patients with sickle cell disease.

    Science.gov (United States)

    Siciliano, Angela; Turrini, Franco; Bertoldi, Mariarita; Matte, Alessandro; Pantaleo, Antonella; Olivieri, Oliviero; De Franceschi, Lucia

    2010-04-15

    Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder related to the production of a defective form of hemoglobin, hemoglobin S (HbS). One of the hallmarks of SCD is the presence of dense, dehydrate highly adhesive sickle red blood cells (RBCs) that result from persistent membrane damage associated with HbS polymerization, abnormal activation of membrane cation transports and generation of distorted and rigid red cells with membrane perturbation and cytoskeleton dysfunction. Although modulation of phosphorylation state of the proteins from membrane and cytoskeleton networks has been proposed to participate in red cell homeostasis, much still remains to be investigated in normal and diseased red cells. Here, we report that tyrosine (Tyr-) phosphoproteome of sickle red cells was different from normal controls and was affected by deoxygenation. We found proteins, p55 and band 4.1, from the junctional complex, differently Tyr-phosphorylated in SCD RBCs compared to normal RBCs under normoxia and modulated by deoxygenation, while band 4.2 was similarly Tyr-phosphorylated in both conditions. In SCD RBCs we identified the phosphopeptides for protein 4.1R located in the protein FERM domain (Tyr-13) and for alpha-spectrin located near or in a linker region (Tyr-422 and Tyr-1498) involving protein areas crucial for their functions in the context of red cell membrane properties, suggesting that Tyr-phosphorylation may be part of the events involved in maintaining membrane mechanical stability in SCD red cells.

  12. Phospholipases A2 and neural membrane dynamics: implications for Alzheimer's disease.

    Science.gov (United States)

    Lee, James C-M; Simonyi, Agnes; Sun, Albert Y; Sun, Grace Y

    2011-03-01

    Phospholipases A(2) (PLA(2)s) are essential enzymes in cells. They are not only responsible for maintaining the structural organization of cell membranes, but also play a pivotal role in the regulation of cell functions. Activation of PLA(2) s results in the release of fatty acids and lysophospholipids, products that are lipid mediators and compounds capable of altering membrane microdomains and physical properties. Although not fully understood, recent studies have linked aberrant PLA(2) activity to oxidative signaling pathways involving NADPH oxidase that underlie the pathophysiology of a number of neurodegenerative diseases. In this paper, we review studies describing the involvement of cytosolic PLA(2) in oxidative signaling pathways leading to neuronal impairment and activation of glial cell inflammatory responses. In addition, this review also includes information on the role of cytosolic PLA(2) and exogenous secretory PLA(2) on membrane physical properties, dynamics, and membrane proteins. Unraveling the mechanisms that regulate specific types of PLA(2)s and their effects on membrane dynamics are important prerequisites towards understanding their roles in the pathophysiology of Alzheimer's disease, and in the development of novel therapeutics to retard progression of the disease.

  13. Chronic kidney disease predicts impaired membrane microviscosity of red blood cells in hypertensive and normotensive subjects.

    Science.gov (United States)

    Tsuda, Kazushi

    2013-01-01

    Current evidence indicates that abnormalities in physical properties of the cell membranes may be strongly linked to hypertension and other circulatory disorders. Recent studies have shown that chronic kidney disease (CKD) might be a risk factor for cardiovascular and cerebrovascular outcomes. The purpose of the present study was to examine the possible relationship between kidney function and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive subjects using an electron spin resonance (ESR) and spin-labeling method. The order parameter (S) for the ESR spin-label agent (5-nitroxide stearate) in RBC membranes was significantly higher in hypertensive subjects than in normotensive subjects, indicating that membrane fluidity was decreased in hypertension. The order parameter (S) of RBCs was inversely correlated with estimated glomerular filtration rate (eGFR), suggesting that a decreased eGFR value might be associated with reduced membrane fluidity of RBCs. Multivariate regression analysis also demonstrated that, after adjustment for general risk factors, eGFR might be a significant predictor of membrane fluidity of RBCs. The reduced levels of both membrane fluidity of RBCs and eGFR were associated with increased plasma 8-iso-prostaglandin F2α (an index of oxidative stress) and decreased plasma nitric oxide (NO)-metabolites, suggesting that kidney function could be a determinant of membrane microviscosity of RBCs, at least in part, via oxidative stress- and NO-dependent mechanisms. The ESR study suggests that CKD might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory disorders in hypertensive subjects.

  14. Pulmonary Changes in Preterm Neonates with Hyaline Membrane Disease (a Clinicomorphological Study

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2009-01-01

    Full Text Available Objective: to reveal lung morphological changes in preterm neonatal infants with hyaline membrane disease (HMD in the use of exogenous surfactants and artificial ventilation. Materials and methods. Case histories and autopsy protocols were analyzed in 90 preterm neonates who had died from severe respiratory failure. All the neonates were divided into 4 groups: 1 20 (22.2% infants who had received the exogenous surfactant Curosurf in the combined therapy of HMD; 2 19 (21.1% babies with HMD who had taken Surfactant BL; 3 25 (27.8% surfactant-untreated infants who had died from HMD; 4 26 (28.9% very preterm neonates with extremely low birth weight who had died within the first hour of life. The lungs were histologically and morphometrically examined. Results. The study demonstrated the specific course of HMD when exogenous surfactants and artificial ventilation were used. The contributors to the development of the disease are intranatal amniotic fluid aspiration and intranatal fetal hypoxia. Conclusion. Artificial ventilation and the use of exogenous surfactants do not block the generation of hyaline membranes. The latter differ in formation time, form, and location. The differences in a cell response to hyaline membranes were found in the neonatal infants receiving exogenous surfactants. The characteristic morphological signs of the disease for all the neonates enrolled in the study are alveolar and bronchial epithelial damages and microcirculatory disorders. Key words: preterm neonatal infants, hyaline membrane disease, exogenous surfactants, artificial ventilation, histology, morphometry.

  15. Goodpasture disease as a consequence of melioidosis.

    Science.gov (United States)

    Mackintosh, D; Mantha, M; Oliver, K

    2016-12-01

    We describe a case of anti-glomerular basement membrane (GBM) antibody-mediated disease in association with concomitant Burkholderia pseudomallei (melioidosis) bacteraemia. The temporal profile of the illness and initial absence of circulating anti-GBM antibodies, in light of the subsequent definitive histological diagnosis of anti-GBM disease, makes this case interesting and unusual. Additionally, there have been no prior case reports suggesting melioidosis as a cause of biopsy-proven glomerulonephritis. © 2016 Royal Australasian College of Physicians.

  16. Attachment of cells to basement membrane collagen type IV

    OpenAIRE

    1986-01-01

    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...

  17. Mouse endometrial stromal cells produce basement-membrane components

    DEFF Research Database (Denmark)

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

    1986-01-01

    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...

  18. Bullous Pemphigoid With a Dual Pattern of Glomerular Immune Complex Disease

    NARCIS (Netherlands)

    Hoorn, Ewout J.; Taams, Noor E.; Hurskainen, Tiina; Salih, Mahdi; Weening, Jan J.; Jonkman, Marcel F.; Pas, Hendri H.; Schreurs, Marco W. J.

    2016-01-01

    A 75-year-old man presented with a blistering skin disease and nephrotic syndrome. Bullous pemphigoid was diagnosed by linear immunoglobulin G (IgG) and C3 staining along the basement membrane zone of a skin biopsy specimen and by the presence of circulating IgG recognizing the 180-kDa bullous pemph

  19. Bone marrow stroma in idiopathic myelofibrosis and other haematological diseases. An immunohistochemical study

    DEFF Research Database (Denmark)

    Lisse, I; Hasselbalch, H; Junker, P

    1991-01-01

    Bone marrow stroma was investigated immunohistochemically in 31 patients with haematological diseases, mainly idiopathic myelofibrosis (n = 8) and related chronic myeloproliferative disorders (n = 14). The bone marrow from patients with idiopathic myelofibrosis and some CML patients showed marked...... and capillarization, with the development of continuous sheets of basement membrane material beneath endothelial cells....

  20. Bullous Pemphigoid With a Dual Pattern of Glomerular Immune Complex Disease

    NARCIS (Netherlands)

    Hoorn, Ewout J.; Taams, Noor E.; Hurskainen, Tiina; Salih, Mahdi; Weening, Jan J.; Jonkman, Marcel F.; Pas, Hendri H.; Schreurs, Marco W. J.

    A 75-year-old man presented with a blistering skin disease and nephrotic syndrome. Bullous pemphigoid was diagnosed by linear immunoglobulin G (IgG) and C3 staining along the basement membrane zone of a skin biopsy specimen and by the presence of circulating IgG recognizing the 180-kDa bullous

  1. Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting.

    Science.gov (United States)

    Rajendran, Lawrence; Schneider, Anja; Schlechtingen, Georg; Weidlich, Sebastian; Ries, Jonas; Braxmeier, Tobias; Schwille, Petra; Schulz, Jörg B; Schroeder, Cornelia; Simons, Mikael; Jennings, Gary; Knölker, Hans-Joachim; Simons, Kai

    2008-04-25

    beta-Secretase plays a critical role in beta-amyloid formation and thus provides a therapeutic target for Alzheimer's disease. Inhibitor design has usually focused on active-site binding, neglecting the subcellular localization of active enzyme. We have addressed this issue by synthesizing a membrane-anchored version of a beta-secretase transition-state inhibitor by linking it to a sterol moiety. Thus, we targeted the inhibitor to active beta-secretase found in endosomes and also reduced the dimensionality of the inhibitor, increasing its local membrane concentration. This inhibitor reduced enzyme activity much more efficiently than did the free inhibitor in cultured cells and in vivo. In addition to effectively targeting beta-secretase, this strategy could also be used in designing potent drugs against other membrane protein targets.

  2. Report on the 53rd Annual Meeting of the Canadian Society of Biochemistry, Molecular and Cellular Biology: "Membrane Proteins in Health and Disease".

    Science.gov (United States)

    Reithmeier, Reinhart A F; Casey, Joseph R

    2011-04-01

    The meeting "Membrane Proteins in Health and Disease" featured 6 sessions and 2 satellite meetings. At the opening session, Gunnar von Heijne delivered a plenary lecture entitled Insertion of Membrane Proteins into the Endoplasmic Reticulum. The following session topics were Membrane Protein Trafficking and Folding, Regulation of Membrane Proteins, Membrane Protein Structure, Membrane Proteins in Diverse Species, and Membrane Proteins and Diseases. The satellite meetings discussed bicarbonate transporters and Na+/H+ exchangers. Together the 21 lectures and 106 posters presented at the meeting spanned the full spectrum of current research into membrane protein structure and function.

  3. Knockdown of cytosolic glutaredoxin 1 leads to loss of mitochondrial membrane potential: implication in neurodegenerative diseases.

    Directory of Open Access Journals (Sweden)

    Uzma Saeed

    Full Text Available Mitochondrial dysfunction including that caused by oxidative stress has been implicated in the pathogenesis of neurodegenerative diseases. Glutaredoxin 1 (Grx1, a cytosolic thiol disulfide oxido-reductase, reduces glutathionylated proteins to protein thiols and helps maintain redox status of proteins during oxidative stress. Grx1 downregulation aggravates mitochondrial dysfunction in animal models of neurodegenerative diseases, such as Parkinson's and motor neuron disease. We examined the mechanism underlying the regulation of mitochondrial function by Grx1. Downregulation of Grx1 by shRNA results in loss of mitochondrial membrane potential (MMP, which is prevented by the thiol antioxidant, alpha-lipoic acid, or by cyclosporine A, an inhibitor of mitochondrial permeability transition. The thiol groups of voltage dependent anion channel (VDAC, an outer membrane protein in mitochondria but not adenosine nucleotide translocase (ANT, an inner membrane protein, are oxidized when Grx1 is downregulated. We then examined the effect of beta-N-oxalyl amino-L-alanine (L-BOAA, an excitatory amino acid implicated in neurolathyrism (a type of motor neuron disease, that causes mitochondrial dysfunction. Exposure of cells to L-BOAA resulted in loss of MMP, which was prevented by overexpression of Grx1. Grx1 expression is regulated by estrogen in the CNS and treatment of SH-SY5Y cells with estrogen upregulated Grx1 and protected from L-BOAA mediated MMP loss. Our studies demonstrate that Grx1, a cytosolic oxido-reductase, helps maintain mitochondrial integrity and prevents MMP loss caused by oxidative insult. Further, downregulation of Grx1 leads to mitochondrial dysfunction through oxidative modification of the outer membrane protein, VDAC, providing support for the critical role of Grx1 in maintenance of MMP.

  4. Bullous Pemphigoid With a Dual Pattern of Glomerular Immune Complex Disease.

    Science.gov (United States)

    Hoorn, Ewout J; Taams, Noor E; Hurskainen, Tiina; Salih, Mahdi; Weening, Jan J; Jonkman, Marcel F; Pas, Hendri H; Schreurs, Marco W J

    2016-02-01

    A 75-year-old man presented with a blistering skin disease and nephrotic syndrome. Bullous pemphigoid was diagnosed by linear immunoglobulin G (IgG) and C3 staining along the basement membrane zone of a skin biopsy specimen and by the presence of circulating IgG recognizing the 180-kDa bullous pemphigoid antigen (BP180; type XVII collagen). A kidney biopsy specimen showed endocapillary inflammation without crescents. Direct immunofluorescence showed strong IgG and C3 staining in a combined granular and linear pattern along the glomerular basement membrane. Electron microscopy showed subepithelial deposits. In serum, no antibodies against the Goodpasture antigen (type IV collagen) or phospholipase A2 receptor were detected. Indirect immunofluorescence studies using the patient's serum showed a strikingly linear but not granular IgG pattern along the epithelial basement membranes of monkey esophagus and kidney. Although type XVII collagen was recently identified in the glomerulus, the patient's serum did not produce a 180-kDa band on immunoblot of kidney tissue and still stained glomeruli of BP180 knockout mice by indirect immunofluorescence. The patient was treated with prednisone and azathioprine, which resulted in complete remission of skin and kidney manifestations. Although bullous pemphigoid has been reported previously in association with anti-glomerular basement membrane disease or membranous nephropathy, this case demonstrates both elements in 1 patient. This concurrence and the linear pattern on indirect immunofluorescence support the possibility of cross-reactive or parallel autoantibodies to basement membranes with a secondary membranous component. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  5. Models of plasma membrane organization can be applied to mitochondrial membranes to target human health and disease with polyunsaturated fatty acids.

    Science.gov (United States)

    Raza Shaikh, Saame; Brown, David A

    2013-01-01

    Bioactive n-3 polyunsaturated fatty acids (PUFA), abundant in fish oil, have potential for treating symptoms associated with inflammatory and metabolic disorders; therefore, it is essential to determine their fundamental molecular mechanisms. Recently, several labs have demonstrated the n-3 PUFA docosahexaenoic acid (DHA) exerts anti-inflammatory effects by targeting the molecular organization of plasma membrane microdomains. Here we briefly review the evidence that DHA reorganizes the spatial distribution of microdomains in several model systems. We then emphasize how models on DHA and plasma membrane microdomains can be applied to mitochondrial membranes. We discuss the role of DHA acyl chains in regulating mitochondrial lipid-protein clustering, and how these changes alter several aspects of mitochondrial function. In particular, we summarize effects of DHA on mitochondrial respiration, electron leak, permeability transition, and mitochondrial calcium handling. Finally, we conclude by postulating future experiments that will augment our understanding of DHA-dependent membrane organization in health and disease.

  6. Hyaline membrane disease or respiratory distress syndrome? A new approach for an old disease

    Directory of Open Access Journals (Sweden)

    Lidia Grappone

    2014-06-01

    Full Text Available The term “hyaline membrane disease” refers to the histological aspect of the most frequent pulmonary pathology in preterm newborn patients. The lung of the preterm baby is morphologically and functionally immature. Surfactant deficiency in the immature lungs causes alveolar instability and collapse, capillary edema and the formation of hyaline membrane. Thus, the hyaline membranes are epiphenomena and are not the cause of respiratory failure in infants with immature lungs. This definition is presently used to indicate surfactant deficit alone and should not be used for other causes of respiratory distress. Clinicians prefer to talk of “respiratory distress syndrome” (RDS. Improvement in neonatal treatment has changed the natural course of the illness, its clinical and radiological features and has enabled extremely low birth weight newborns (ELBW to survive. Alveoli paucity and pulmonary interstitial thickness in ELBW impair gas exchange and may necessitate prolonged ventilation treatment, increasing the risk of ventilator-induced lung injury (VILI and bronchopulmonary dysplasia (BPD. RDS, therefore, is a complex illness where pulmonary immaturity and surfactant deficit play a role together with other pathological conditions that determine the course of the illness and both short and long-term results. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  7. Oral manifestations caused by the linear IgA disease.

    Science.gov (United States)

    Eguia del Valle, Asier; Aguirre Urízar, José Manuel; Martínez Sahuquillo, Angel

    2004-01-01

    The Linear IgA deposit related disease or Linear IgA disease (LAD) is a chronic, uncommon and autoimmunological mucocutaneous disease, characterised by linear IgA deposits along the basement membrane zone. In mainly cases, moreover cutaneous lesions, there are oral mucosal and other mucosal lesions. There are also, some cases published of Linear IgA disease limited to oral mucosa. The known of this disease is important for the establishment of a correct differential diagnosis in cases of blistering mucocutaneous diseases. In this paper, we analyze the most important features of this disease, attending specially to the oral manifestations.

  8. A case of membranous nephropathy as a manifestation of graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Jae Hyun Han

    2013-03-01

    Full Text Available Nephrotic syndrome (NS rarely occurs after hematopoietic stem cell transplantation (HSCT as a late manifestation of graft-versus-host disease (GVHD. Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.

  9. Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria.

    Science.gov (United States)

    Schönfeld, P; Struy, H

    1999-08-27

    Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a branched chain fatty acid accumulating in Refsum disease to high levels throughout the body, induces uncoupling of rat liver mitochondria similar to non-branched fatty acids (e.g. palmitic acid), but the contribution of the ADP/ATP carrier or the aspartate/glutamate carrier in phytanic acid-induced uncoupling is of minor importance. Possible deleterious effects of phytanic acid on membrane-linked energy coupling processes were studied by ESR spectroscopy using rat liver mitochondria and a membrane preparation labeled with the lipid-specific spin probe 5-doxylstearic acid (5-DSA) or the protein-specific spin probe MAL-TEMPO (4-maleimido-2,2,6, 6-tetramethyl-piperidine-1-oxyl). The effects of phytanic acid on phospholipid molecular dynamics and on the physical state of membrane proteins were quantified by estimation of the order parameter or the ratio of the amplitudes of the weakly to strongly immobilized MAL-TEMPO binding sites (W/S ratio), respectively. It was found, that phytanic acid (1) increased the mobility of phospholipid molecules (indicated by a decrease in the order parameter) and (2) altered the conformational state and/or the segmental mobility of membrane proteins (indicated by a drastic decrease in the W/S ratio). Unsaturated fatty acids with multiple cis-double bonds (e.g. linolenic or arachidonic acid), but not non-branched FFA (ranging from chain length C10:0 to C18:0), also decrease the W/S ratio. It is hypothesized that the interaction of phytanic acid with transmembrane proteins might stimulate the proton permeability through the mitochondrial inner membrane according to a mechanism, different to a protein-supported fatty acid cycling.

  10. Treatment of periodontal disease with guided tissue regeneration technique using a hydroxyapatite and polycaprolactone membrane

    Directory of Open Access Journals (Sweden)

    L.M.A. Martins

    Full Text Available ABSTRACT The aim of this study was to evaluate the use of a malleable membrane composed of hydroxyapatite (60% and polycaprolactone (40% as treatment of periodontal disease experimentally induced in dogs. A bone defect of standardized dimensions was created between the roots of the third and fourth premolar of 12 dogs for periodontal disease induction. Six dogs had the defect covered by the membrane and six dogs received only standard treatment for periodontal disease, also applied to dogs in the treated group. The animals were clinically monitored during the experiment. Radiographs were taken after surgery and at 60 days after treatment initiation. Clinical attachment level was also assessed in those moments. On the 60th day, dental sample of all animals, containing tooth, defect and periodontal tissues, were harvested, fixed in formalin and analyzed by microtomography and histology. During the experimental period, the animals showed no pain and purulent discharge, however, there was dehiscence in 50% of animals and membrane exposure in five out of six animals in the treated group. Clinical attachment level showed no difference between groups. Radiographs showed radiopacity equal to the alveolar bone in both groups. The microtomography revealed that the control group had higher bone volume in the defect compared to the treated group; however, the furcation was not filled by new alveolar bone in any animal. Histological analysis revealed that junctional epithelium invasion was lighter in the control group. New bone was only observed in the apical edge of the defect in both groups. Although the composite is biocompatible and able to keep the space of the defect, it did not promote periodontal tissue regeneration within 60 days of observation.

  11. Choroideremia Is a Systemic Disease With Lymphocyte Crystals and Plasma Lipid and RBC Membrane Abnormalities

    Science.gov (United States)

    Zhang, Alice Yang; Mysore, Naveen; Vali, Hojatollah; Koenekoop, Jamie; Cao, Sang Ni; Li, Shen; Ren, Huanan; Keser, Vafa; Lopez-Solache, Irma; Siddiqui, Sorath Noorani; Khan, Ayesha; Mui, Jeannie; Sears, Kelly; Dixon, Jim; Schwartzentruber, Jeremy; Majewski, Jacek; Braverman, Nancy; Koenekoop, Robert K.

    2015-01-01

    Purpose Photoreceptor neuronal degenerations are common, incurable causes of human blindness affecting 1 in 2000 patients worldwide. Only half of all patients are associated with known mutations in over 250 disease genes, prompting our research program to identify the remaining new genes. Most retinal degenerations are restricted to the retina, but photoreceptor degenerations can also be found in a wide variety of systemic diseases. We identified an X-linked family from Sri Lanka with a severe choroidal degeneration and postulated a new disease entity. Because of phenotypic overlaps with Bietti's crystalline dystrophy, which was recently found to have systemic features, we hypothesized that a systemic disease may be present in this new disease as well. Methods For phenotyping, we performed detailed eye exams with in vivo retinal imaging by optical coherence tomography. For genotyping, we performed whole exome sequencing, followed by Sanger sequencing confirmations and cosegregation. Systemic investigations included electron microscopy studies of peripheral blood cells in patients and in normal controls and detailed fatty acid profiles (both plasma and red blood cell [RBC] membranes). Fatty acid levels were compared to normal controls, and only values two standard deviations above or below normal controls were further evaluated. Results The family segregated a REP1 mutation, suggesting choroideremia (CHM). We then found crystals in peripheral blood lymphocytes and discovered significant plasma fatty acid abnormalities and RBC membrane abnormalities (i.e., elevated plasmalogens). To replicate our discoveries, we expanded the cohort to nine CHM patients, genotyped them for REP1 mutations, and found the same abnormalities (crystals and fatty acid abnormalities) in all patients. Conclusions Previously, CHM was thought to be restricted to the retina. We show, to our knowledge for the first time, that CHM is a systemic condition with prominent crystals in lymphocytes and

  12. Treatment strategies in mucous membrane pemphigoid

    Directory of Open Access Journals (Sweden)

    Ann G Neff

    2008-06-01

    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

  13. Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.

    Science.gov (United States)

    Pinheiro, Marina; Giner-Casares, Juan J; Lúcio, Marlene; Caio, João M; Moiteiro, Cristina; Lima, José L F C; Reis, Salette; Camacho, Luis

    2013-02-01

    This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N'-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents.

  14. Mitochondrial-dependent Autoimmunity in Membranous Nephropathy of IgG4-related Disease

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    Simona Buelli

    2015-05-01

    Full Text Available The pathophysiology of glomerular lesions of membranous nephropathy (MN, including seldom-reported IgG4-related disease, is still elusive. Unlike in idiopathic MN where IgG4 prevails, in this patient IgG3 was predominant in glomerular deposits in the absence of circulating anti-phospholipase A2 receptor antibodies, suggesting a distinct pathologic process. Here we documented that IgG4 retrieved from the serum of our propositus reacted against carbonic anhydrase II (CAII at the podocyte surface. In patient's biopsy, glomerular CAII staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls. Patient's IgG4 caused a drop in cell pH followed by mitochondrial dysfunction, excessive ROS production and cytoskeletal reorganization in cultured podocytes. These events promoted mitochondrial superoxide-dismutase-2 (SOD2 externalization on the plasma membrane, becoming recognizable by complement-binding IgG3 anti-SOD2. Among patients with IgG4-related disease only sera of those with IgG4 anti-CAII antibodies caused low intracellular pH and mitochondrial alterations underlying SOD2 externalization. Circulating IgG4 anti-CAII can cause podocyte injury through processes of intracellular acidification, mitochondrial oxidative stress and neoantigen induction in patients with IgG4 related disease. The onset of MN in a subset of patients could be due to IgG4 antibodies recognizing CAII with consequent exposure of mitochondrial neoantigen in the context of multifactorial pathogenesis of disease.

  15. Radiologic and histologic features of hyaline membrane diseases of the newbone

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Seung Yon; Choi, Kyung Hee; Suh, Jeong Soo; Rhee, Chung Sik; Kim, Hee Seup [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    1984-12-15

    This study represents the radiologic, histologic features and clinical analysis of hyaline membrane diseases in 47 newbone infants who were delivered in Ewha Womans Univ. Hospital and expired caused by respiratory distress and confirmed by autopsy, during Jan. 1981 to June. 1984. The results were as follows: 1. Classification of radiographic stage (by Wolfson's criteria); Stage III (34.1%) was the most frequent. 2. Male to female ratio was 2.4 : 1. 3. Method of delivery; Cesarean section (44.7%) was the highest frequency, compared with percent of cesarean section to total delivery (29.0%) 4. Distribution of birth weight; 1.0-2.0 kg (48.9%) was the most frequent. 5. Distribution of gestational period; 32-36 weeks (29.8%) was the most frequent. 6. Complication; pulmonary hemorrhage (31.9%) was the most frequent, in order, subarachnoid hemorrhage and pneumothorax were followed. 7. Final diagnosis of hyaline membrane diseases was based on histo-pathologic diagnosis.

  16. Antibodies against analogous heptad repeat peptide HR212 of Newcastle Disease Virus inhibit virus-cell membrane fusion

    Institute of Scientific and Technical Information of China (English)

    LI Ying; TIEN Po

    2007-01-01

    Membrane fusion is a key step in enveloped virus entry. Highly conserved heptad repeat regions (HR1 and HR2) of Newcastle disease virus (NDV) fusion protein (F) are critical functional domains for viral membrane fusion. They display different conformations in the membrane fusion states and are viewed as candidate targets for neutralizing antibody responses. We previously reported that an analog of heptad repeat peptides HR2-HR1-HR2(HR212) and HR2 could inhibit NDV induced cell-cell membrane fusion. Here, we show that HR212 can induce the production of highly potent antibody in immunized rabbits, which could recognize full length peptides of both HR1 and HR2, and inhibit NDV hemagglutination and NDV entry. These suggest that either HR212 or its antibody could be an inhibitor of virus-induced cell-cell membrane fusion.

  17. Role of Mitochondria-Associated Endoplasmic Reticulum Membrane in Inflammation-Mediated Metabolic Diseases.

    Science.gov (United States)

    Thoudam, Themis; Jeon, Jae-Han; Ha, Chae-Myeong; Lee, In-Kyu

    2016-01-01

    Inflammation is considered to be one of the most critical factors involved in the development of complex metabolic diseases such as type 2 diabetes, cancer, and cardiovascular disease. A few decades ago, the discovery of mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) was followed by the identification of its roles in regulating cellular homeostatic processes, ranging from cellular bioenergetics to apoptosis. MAM provides an excellent platform for numerous signaling pathways; among them, inflammatory signaling pathways associated with MAM play a critical role in cellular defense during pathogenic infections and metabolic disorders. However, induction of MAM causes deleterious effects by amplifying mitochondrial reactive oxygen species generation through increased calcium transfer from the ER to mitochondria, thereby causing mitochondrial damage and release of mitochondrial components into the cytosol as damage-associated molecular patterns (DAMPs). These mitochondrial DAMPs rapidly activate MAM-resident inflammasome components and other inflammatory factors, which promote inflammasome complex formation and release of proinflammatory cytokines in pathological conditions. Long-term stimulation of the inflammasome instigates chronic inflammation, leading to the pathogenesis of metabolic diseases. In this review, we summarize the current understanding of MAM and its association with inflammation-mediated metabolic diseases.

  18. Magnetotelluric inversion for depth-to-basement estimation

    DEFF Research Database (Denmark)

    Cai, Hongzhu; Zhdanov, Michael

    2015-01-01

    The magnetotelluric (MT) method can be effectively applied for depth-to-basement estimation, because there exists a strong contrast in resistivity between a conductive sedimentary basin and a resistive crystalline basement. Conventional inversions of MT data are usually aimed at determining...

  19. Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease: A Retrospective Study of 10 Cases.

    Science.gov (United States)

    Dauvergne, Maxime; Moktefi, Anissa; Rabant, Marion; Vigneau, Cécile; Kofman, Tomek; Burtey, Stephane; Corpechot, Christophe; Stehlé, Thomas; Desvaux, Dominique; Rioux-Leclercq, Nathalie; Rouvier, Philippe; Knebelmann, Bertrand; Boffa, Jean-Jacques; Frouget, Thierry; Daugas, Eric; Jablonski, Mathieu; Dahan, Karine; Brocheriou, Isabelle; Remy, Philippe; Grimbert, Philippe; Lang, Philippe; Chazouilleres, Oliver; Sahali, Dil; Audard, Vincent

    2015-07-01

    The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens.The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating.Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN.

  20. Cerebral involvement in a patient with Goodpasture's disease due to shortened induction therapy: a case report

    Directory of Open Access Journals (Sweden)

    Preul Christoph

    2009-11-01

    Full Text Available Abstract Introduction Goodpasture's disease is a rare immunological disease with formation of pathognomonic antibodies against renal and pulmonary basement membranes. Cerebral involvement has been reported in several cases in the literature, yet the pathogenetic mechanism is not entirely clear. Case presentation A 21-year-old Caucasian man with Goodpasture's disease and end-stage renal disease presented with two generalized seizures after a period of mild cognitive disturbance. Blood pressure and routine laboratory tests did not exceed the patient's usual values, and examination of cerebrospinal fluid was unremarkable. Cerebral magnetic resonance imaging (MRI revealed multiple cortical and subcortical lesions on fluid-attenuated inversion recovery sequences. Since antiglomerular basement membrane antibodies were found to be positive with high titers, plasmapheresis was started. In addition, cyclophosphamide pulse therapy was given on day 13. Encephalopathy and MRI lesions disappeared during this therapy, and antiglomerular basement membrane antibodies were significantly reduced. Previous immunosuppressive therapy was performed without corticosteroids and terminated early after 3 months. The differential diagnostic considerations were cerebral vasculitis and posterior reversible encephalopathy syndrome. Vasculitis could be seen as an extrarenal manifestation of the underlying disease. Posterior reversible encephalopathy syndrome, on the other hand, can be triggered by immunosuppressive therapy and may appear without a hypertensive crisis. Conclusion A combination of central nervous system symptoms with a positive antiglomerular basement membrane test in a patient with Goodpasture's disease should immediately be treated as an acute exacerbation of the disease with likely cross-reactivity of antibodies with the choroid plexus. In our patient, a discontinuous strategy of immunosuppressive therapy may have favored recurrence of Goodpasture's disease.

  1. Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

    Science.gov (United States)

    Liu, Kui; Li, Quan-Zhen; Delgado-Vega, Angelica M.; Abelson, Anna-Karin; Sánchez, Elena; Kelly, Jennifer A.; Li, Li; Liu, Yang; Zhou, Jinchun; Yan, Mei; Ye, Qiu; Liu, Shenxi; Xie, Chun; Zhou, Xin J.; Chung, Sharon A.; Pons-Estel, Bernardo; Witte, Torsten; de Ramón, Enrique; Bae, Sang-Cheol; Barizzone, Nadia; Sebastiani, Gian Domenico; Merrill, Joan T.; Gregersen, Peter K.; Gilkeson, Gary G.; Kimberly, Robert P.; Vyse, Timothy J.; Kim, Il; D’Alfonso, Sandra; Martin, Javier; Harley, John B.; Criswell, Lindsey A.; Wakeland, Edward K.; Alarcón-Riquelme, Marta E.; Mohan, Chandra

    2009-01-01

    Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody–induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody–induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody–induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody–induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody–induced nephritis and lupus. PMID:19307730

  2. Influence of denture plaque biofilm on oral mucosal membrane in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Przybyłowska, D; Mierzwińska-Nastalska, E; Rubinsztajn, R; Chazan, R; Rolski, D; Swoboda-Kopeć, E

    2015-01-01

    Patients with chronic obstructive pulmonary disease (COPD) have the lower airways colonized with pathogenic bacteria in a stable period of the disease and during exacerbations. The etiology of bacterial exacerbations of COPD depends on the underlying disease, the frequency of exacerbations and antibiotic therapy. Microorganisms can be aspirated off the denture plaque biofilm into the lower respiratory tract and could reduce the patient's immunity and cause pneumonia. COPD patients, who are using acrylic dentures in oral cavity, are exposed to denture stomatitis and oral candidiasis. The aim of this study was to establish the composition of denture plaque biofilm and its impact on the oral mucosa in COPD patients. The study included patients in a stable phase of COPD using removable denture and the control group included healthy wearer's appliances. Examinations concerned the oral mucosal membrane and the hygienic condition of prosthetic restorations. Microbiological examinations were performed by taking a direct swab from the surface of acrylic dentures. Seventeen bacterial and fungal strains were isolated from denture plaque of COPD patients, which could be a reservoir of pathogens in the upper and lower airways. The results showed a greater frequency of prosthetic stomatitis complicated by mucosal infections among COPD patients compared to healthy subjects.

  3. Changes of cerebral hemodynamics following the administration of surfactant in the hyaline membrane disease of prematurity

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Jeong Hyun; Kim, Kyung Hee [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    2000-09-15

    To evaluate the changes of cerebral blood flow velocity according to the time, before and after surfactant administration in hyaline membrane disease using Doppler ultrasonography. The patients were 15 premature babies who were clinically and radiologically diagnosed HMD. The ratio of male : female was 11:4, the mean gestational age was 30.1 {+-} 2.5 wks, mean body weight was 1.4 {+-} 0.6 kg,mean Apgar score at 5 min was 6.28, and type of delivery was C-section : vaginal delivery 9.6. Before and after, 10 mm, 30 min, 1 hr, 6 hr, 12 hr, 1 day, 3 day, 5 day and 7 day after surfactant administration, peak systolic and end-diastolic cerebral blood flow velocity (PSFV, EDFV) and resistive index (RI) were estimated by Doppler ultrasonography measuring MCA flow velocity using temporal window. The averages of all data according to the time were obtained and analyzed statistical significance. For the evaluation of the clinical status systemic BP, FiO2, pH, and respiratory rate were also checked according to the same time. The clinical status of FiO2, metabolic acidosis, and tachypnea was significantly improved after surfactant administration. There was no significant change of cerebral blood flow velocity (PSFV, EDFV) after the surfactant administration. The change of RI was nor statistically significant. The changes of the systemic BP had no significant changes. In spite of clinical improvement, there were no significant increases of cerebral blood flow velocity and changes of RI after surfactant administration in hyaline membrane disease.

  4. [Goodpasture disease].

    Science.gov (United States)

    Fomegné, G; Dratwa, M; Wens, R; Mesquita, M; Van der Straaten, M; Vanden Haute, K; Fosso, C

    2006-01-01

    We report one case of acute renal failure with oliguria, microscopic haematuria and normocytic anemia in a 86-year old Swedish woman. A full investigation led to the diagnosis of Goodpasture disease, an isolated form of Goodpasture syndrome. Goodpasture disease is and autoimmune disorder characterized by the development of autoantibodies to the NC1 domain of the alpha3 chain of type IV collagen, found mainly in glomerular basement membranes (GBM). When the disease affects both the lung and the kidney, it is called Goodpasture syndrome but the pulmonary or renal involvement can be isolated or separated in years. Its pathogenesis is not well known. It occurs essentially in Caucasian subjects, preferentially from Nordic and Anglo-Saxon countries (higher prevalence of HLA DR B1-15 and B1-4 group). Are also mentioned, the exposure to hydrocarbons, rustproof, insecticides and greasy solvents. The annual incidence of Goodpasture syndrome is rare and has been estimated in Europe to be about 0.5 to 1 case per million inhabitants. The isolated renal form represents about 1/3 of the cases. The clinical presentation is characterized by rapidly progressive renal failure with oliguria or anuria and in case of lung involvement, pulmonary hemorrhage responsible of hemoptysis, sometimes massive. Renal biopsy and immunofluorescence analysis play a key role in the diagnosis. The presence of both linear deposits of IgG along the glomerular basement membrane (GBM) and circulating anti-GBM antibodies is of paramount importance. The treatment, which depends on the degree of renal involvement, is based on the association of corticosteroids, cyclophosphamide and plasma exchanges.

  5. Effect of Clopidogrel on Platelet Membrane CD40 Ligand in Coronary Artery Disease Patients Undertaking Percutaneous Coronary Intervention

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To investigate the change and clinical significance of clopidogrel on platelet membrane CD40L in coronary artery disease patients before and after percutaneous coronary intervention (PCI). Methods 30 cases who were diagnosis coronary artery diseases(CAD) by coronary angiography, mean age 56 ± 9 years old. All the patients who had no antiplatelet aggregation contraindication, were treated with standard anti angina pectoris drugs. Before PCI, all the patients took clopidogrel 75 mg per day. Activated platelet membrane CD40L express rate was measured by flow cytometry before and after PCI 6 hours. Results Activated platelet membrane CD40L express rate were 3.73 ± 2.15and 2.46 ± 0.90, respectively in 30 patients before and after PCI 6 hours. Activated platelet membrane CD40L express rate was significantly decrease after PCI 6 hours than that before PCI ( P < 0.01 ). Conclusions Clopidogrel has significance effect on platelet membrane CD40L in coronary artery disease patients undergoing PCI. Clopidogrel can suppression platelet activation and prevent thromboembolism event occurrence.

  6. Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes.

    Directory of Open Access Journals (Sweden)

    Thomas J Carney

    2010-04-01

    Full Text Available Using forward genetics, we have identified the genes mutated in two classes of zebrafish fin mutants. The mutants of the first class are characterized by defects in embryonic fin morphogenesis, which are due to mutations in a Laminin subunit or an Integrin alpha receptor, respectively. The mutants of the second class display characteristic blistering underneath the basement membrane of the fin epidermis. Three of them are due to mutations in zebrafish orthologues of FRAS1, FREM1, or FREM2, large basement membrane protein encoding genes that are mutated in mouse bleb mutants and in human patients suffering from Fraser Syndrome, a rare congenital condition characterized by syndactyly and cryptophthalmos. Fin blistering in a fourth group of zebrafish mutants is caused by mutations in Hemicentin1 (Hmcn1, another large extracellular matrix protein the function of which in vertebrates was hitherto unknown. Our mutant and dose-dependent interaction data suggest a potential involvement of Hmcn1 in Fraser complex-dependent basement membrane anchorage. Furthermore, we present biochemical and genetic data suggesting a role for the proprotein convertase FurinA in zebrafish fin development and cell surface shedding of Fras1 and Frem2, thereby allowing proper localization of the proteins within the basement membrane of forming fins. Finally, we identify the extracellular matrix protein Fibrillin2 as an indispensable interaction partner of Hmcn1. Thus we have defined a series of zebrafish mutants modelling Fraser Syndrome and have identified several implicated novel genes that might help to further elucidate the mechanisms of basement membrane anchorage and of the disease's aetiology. In addition, the novel genes might prove helpful to unravel the molecular nature of thus far unresolved cases of the human disease.

  7. Extracorporeal membrane oxygenation in the neonate with congenital renal disease and pulmonary hypoplasia.

    Science.gov (United States)

    Caesar, R E; Packer, M G; Kaplan, G W; Dudell, G G; Guerrant, A L; Griswold, W R; Lemire, J M; Mendoza, S A; Reznik, V M

    1995-11-01

    Extracorporeal membrane oxygenation (ECMO) is an effective treatment modality for the newborn with refractory hypoxemia. Oligohydramnios can be associated with congenital renal disease (CRD) and can result in respiratory insufficiency from pulmonary hypoplasia, delayed lung maturation, and persistent pulmonary hypertension of the newborn. In this retrospective study, the authors reviewed the outcome of four children with CRD who required ECMO in the neonatal period. Between October 1987 and December 1995, ECMO was used in four newborns with CRD and pulmonary hypoplasia unresponsive to maximal medical management. The causes of CRD were urinary obstruction (2), renal dysplasia (1), and vesicoureteral reflux (1). Neonatal survivors of ECMO with CRD had regular follow-up with a nephrologist, urologist, and pediatrician. Developmental history, assessment of renal function, and a nutritional evaluation were recorded on each visit. The follow-up period ranged from 6 months to 5 years. All patients with CRD were successfully weaned from ECMO. One child died, at 1 month of age, because of renal failure. The estimated glomerular filtration rates in the three survivors were 20, 24, and 60 mL/min/1.73 m2. Growth and development have been delayed in two patients. Based on the author's experience, ECMO may improve the survival of neonates with pulmonary hypoplasia and CRD. Factors associated with successful long-term outcome include (1) renal disease amenable to surgical correction, (2) aggressive nutritional support, and (3) a reliable social support system.

  8. An antibody that confers plant disease resistance targets a membrane-bound glyoxal oxidase in Fusarium.

    Science.gov (United States)

    Song, Xiu-Shi; Xing, Shu; Li, He-Ping; Zhang, Jing-Bo; Qu, Bo; Jiang, Jin-He; Fan, Chao; Yang, Peng; Liu, Jin-Long; Hu, Zu-Quan; Xue, Sheng; Liao, Yu-Cai

    2016-05-01

    Plant germplasm resources with natural resistance against globally important toxigenic Fusarium are inadequate. CWP2, a Fusarium genus-specific antibody, confers durable resistance to different Fusarium pathogens that infect cereals and other crops, producing mycotoxins. However, the nature of the CWP2 target is not known. Thus, investigation of the gene coding for the CWP2 antibody target will likely provide critical insights into the mechanism underlying the resistance mediated by this disease-resistance antibody. Immunoblots and mass spectrometry analysis of two-dimensional electrophoresis gels containing cell wall proteins from Fusarium graminearum (Fg) revealed that a glyoxal oxidase (GLX) is the CWP2 antigen. Cellular localization studies showed that GLX is localized to the plasma membrane. This GLX efficiently catalyzes hydrogen peroxide production; this enzymatic activity was specifically inhibited by the CWP2 antibody. GLX-deletion strains of Fg, F. verticillioides (Fv) and F. oxysporum had significantly reduced virulence on plants. The GLX-deletion Fg and Fv strains had markedly reduced mycotoxin accumulation, and the expression of key genes in mycotoxin metabolism was downregulated. This study reveals a single gene-encoded and highly conserved cellular surface antigen that is specifically recognized by the disease-resistance antibody CWP2 and regulates both virulence and mycotoxin biosynthesis in Fusarium species. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  9. Periodontal disease and intra-amniotic complications in women with preterm prelabor rupture of membranes.

    Science.gov (United States)

    Radochova, Vladimira; Kacerovska Musilova, Ivana; Stepan, Martin; Vescicik, Peter; Slezak, Radovan; Jacobsson, Bo; Kacerovsky, Marian

    2017-08-04

    Periodontal disease is frequently suggested as a possible causal factor for preterm delivery. The link between periodontal disease and preterm delivery is a possible translocation of periopathogenic bacteria to the placenta and amniotic fluid as well as a systemic response to this chronic inflammatory disease. However, there is a lack of information on whether there is an association between clinical periodontal status in women with preterm prelabor rupture of membranes (PPROM) and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI). Therefore, the main aim of this study was to evaluate the incidence and severity of periodontal disease in women with PPROM. The secondary aim was to characterize an association between periodontal status and the presence of intra-amniotic PPROM complications (MIAC and/or IAI). Seventy-eight women with PPROM at gestational ages between 24 + 0 and 36 + 6 weeks were included in this study. The samples of amniotic fluid were obtained at admission via transabdominal amniocentesis, and amniotic fluid interleukin (IL)-6 concentrations were determined using a point-of-care test. All women had a full-mouth recording to determine the periodontal and oral hygiene status. Probing pocket depth and clinical attachment loss were measured at four sites on each fully erupted tooth. In total, 45% (35/78) of women with PPROM had periodontal disease. Mild, moderate, and severe periodontal disease was present in 19% (15/78), 19% (15/78), and 6% (5/78) of women, respectively. The presence of MIAC and IAI was found in 28% (22/78) and 26% (20/78) of women, respectively. Periopathogenic bacteria (2 × Streptococcus intermedius and 1 × Fusobacterium nucleatum) was found in the amniotic fluid of 4% (3/78) of women. There were no differences in periodontal status between women with MIAC and/or IAI and women without these intra-amniotic complications. The presence of MIAC and IAI was not related

  10. Deforming Etna's Basement: Implications for Edifice stability.

    Science.gov (United States)

    Bakker, Richard; Benson, Philip; Vinciguerra, Sergio

    2013-04-01

    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. Extracorporeal membrane oxygenation in children with heart disease and down syndrome: a multicenter analysis.

    Science.gov (United States)

    Gupta, Punkaj; Gossett, Jeffrey M; Rycus, Peter T; Prodhan, Parthak

    2014-12-01

    The data on the outcomes of children with heart disease and Down syndrome receiving extracorporeal membrane oxygenation (ECMO) for cardiac or respiratory failure are limited. This study aimed to evaluate morbidity and mortality associated with ECMO in children with Down syndrome and heart disease. Children younger than 18 years undergoing heart surgery and ECMO reported in the Extracorporeal Life Support Organization (ELSO) registry (1998-2011) were included in the study. The registry was queried for the following five heart defects: common atrioventricular (AV) canal, tetralogy of Fallot, truncus arteriosus, transposition of great vessels, and interrupted aortic arch. Data collection included patient characteristics, ECMO characteristics, and outcomes. The outcomes evaluated included mortality, ECMO duration, and length of hospital stay for patients with Down syndrome and those with no Down syndrome. The study enrolled 2,815 patients qualified for inclusion. Of these patients, 121 had Down syndrome, whereas 2,694 had no genetic syndrome and were included in the control group. The median age of the patients was 45 days (interquartile range [IQR] 9-192 days), and the median weight was 3.8 kg (IQR 3.0-6.1 kg). The most common cardiac defects in Down syndrome group were common AV canal (63 %) and tetralogy of Fallot (40 %). The Down syndrome group included older patients with greater body weight than the control group. The mortality rate was lower in the Down syndrome group than in the control group (44 vs. 56 %; p = 0.01). The duration of ECMO and length of hospital stay were similar in the two groups. The findings showed that ECMO can be used for children with heart disease and Down syndrome with good results. The outcomes were comparable between the children with Down syndrome and the children without Down syndrome.

  12. Role of platelet plasma membrane Ca2+-ATPase in health and disease

    Institute of Scientific and Technical Information of China (English)

    William; L; Dean

    2010-01-01

    Platelets have essential roles in both health and disease. Normal platelet function is required for hemostasis.Inhibition of platelet function in disease or by pharmacological treatment results in bleeding disorders.On the other hand,hyperactive platelets lead to heart attack and stroke.Calcium is a major second messenger in platelet activation,and elevated intracellular calcium leads to hyperactive platelets.Elevated platelet calcium has been documented in hypertension and diabetes;both conditions increase the likelihood of heart attack and stroke. Thus,proper regulation of calcium metabolism in the platelet is extremely important.Plasma membrane Ca2+-ATPase(PMCA)is a major player in platelet calcium metabolism since it provides the only significant route for calcium efflux.In keeping with the important role of calcium in platelet function,PMCA is a highly regulated transporter.In human platelets,PMCA is activated by Ca2+/calmodulin,by cAMP-dependent phosphorylation and by calpain-dependent removal of the inhibitory peptide.It is inhibited by tyrosine phosphorylation and calpain-dependent proteolysis.In addition,the cellular location of PMCA is regulated by a PDZ-domain-dependent interaction with the cytoskeleton during platelet activation.Rapid regulation by phosphorylation results in changes in the rate of platelet activation,whereas calpain-dependent proteolysis and interaction with the cytoskeleton appears to regulate later events such as clot retraction.In hypertension and diabetes,PMCA expression is upregulated while activity is decreased, presumably due to tyrosine phosphorylation.Clearly,a more complete understanding of PMCA function in human platelets could result in the identification of new ways to control platelet function in disease states.

  13. Basement configuration of KG offshore basin from magnetic anomalies

    Science.gov (United States)

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

    2016-04-01

    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.

  14. Building America Top Innovations 2012: Basement Insulation Systems

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2013-01-01

    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.

  15. Membrane Biophysics

    CERN Document Server

    Ashrafuzzaman, Mohammad

    2013-01-01

    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.

  16. Basement domain map of the conterminous United States and Alaska

    Science.gov (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

    2015-01-01

    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.

  17. Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ramón Peces

    2011-01-01

    Full Text Available We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD and concomitant nephrotic syndrome secondary to membranous nephropathy (MN. A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI and an angiotensin II receptor blocker (ARB for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

  18. Nephrotic syndrome and idiopathic membranous nephropathy associated with autosomal-dominant polycystic kidney disease.

    Science.gov (United States)

    Peces, Ramón; Martínez-Ara, Jorge; Peces, Carlos; Picazo, Mariluz; Cuesta-López, Emilio; Vega, Cristina; Azorín, Sebastián; Selgas, Rafael

    2011-05-05

    We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

  19. Nuclear membrane protein emerin: roles in gene regulation, actin dynamics and human disease.

    Science.gov (United States)

    Wilson, Katherine L; Holaska, James M; Montes de Oca, Rocio; Tifft, Kathryn; Zastrow, Michael; Segura-Totten, Miriam; Mansharamani, Malini; Bengtsson, Luiza

    2005-01-01

    Loss of emerin, a nuclear membrane protein, causes Emery-Dreifuss muscular dystrophy (EDMD), characterized by muscle weakening, contractures of major tendons and potentially lethal cardiac conduction system defects. Emerin has a LEM-domain and therefore binds barrier-to-autointegration factor (BAF), a conserved chromatin protein essential for cell division. BAF recruits emerin to chromatin and regulates higher-order chromatin structure during nuclear assembly. Emerin also binds filaments formed by A-type lamins, mutations in which also cause EDMD. Other partners for emerin include nesprin-1alpha and transcriptional regulators such as germ cell-less (GCL). The binding affinities of these partners range from 4nM (nesprin-1alpha) to 200 nM (BAF), and are physiologically significant. Biochemical studies therefore provide a valid means to predict the properties of emerin-lamin complexes in vivo. Emerin and lamin A together form stable complexes with either BAF or GCL in vitro. BAF, however, competes with GCL for binding to emerin in vitro. These and additional partners, notably actin and nuclear myosin II, suggest disease-relevant roles for emerin in gene regulation and the mechanical interity of the nucleus.

  20. Roentgenographic findings in hyaline membrane disease treated with exogenous surfactant: comparison with control group

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Kyoung; Lim, Chae Ha; Lim, Woo Young; Kim, Young Sook; Byen, Ju Nam; Oh, Jae Hee; Kim, Young Chul [Chosun Univ. College of Medicine, Kwangju (Korea, Republic of)

    1997-01-01

    To compare, with the use of chest radiographic findings, improvement and complications in newborns treated with exogenous surfactant for hyaline membrane disease (HMD), and an untreated control group. Thirty-six patients with HMD were randomly assigned to a control group (n=18) or surfactant treated group (n=18). As part of an initial evaluation of their pulmonary status, we then performed a retrospective statistical analysis of chest radiographic findings obtained in exogenous surfactant treated and untreated infants within the first 90 minutes of life. Subsequent examinations were performed at less than 24 hours of age. Chest radiograph before treatment showed no significant differences between the two groups, but significant improvement was noted in the surfactant treated group, in contrast to the control group. The most common chest radiographic finding after surfactant administration was uniform (n=15) or disproportionate (n=2) improvement of pulmonary aeration. Patent ductus arteriosus developed in three treated neonates and in four cases in the control group. Air leak occurred in three cases in the treated group and in five cases in the control group. In one treated patient pulmonary hemorrhage developed and intracranial hemorrhage occurred in three treated neonates and in four cases in the control group. Bronchopulmonary dysplasia was developed in 6 cases of treated group and 3 cases of control group. A chest radiograph is considered to be helpful in the evaluation of improvement and complications of HMD in infants treated with surfactant.

  1. Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran

    1997-01-01

    properties of the vessel wall, and the growth regulation of intimal smooth muscle cells. Recent studies have shown that heparin increases the biosynthesis of heparan sulfate in endothelial cell cultures and prevents the characteristic glomerular basement membrane thickening when given to diabetic rats...... in susceptible patients is unknown, but increasing evidence has suggested that loss of the proteoglycan heparan sulfate in the vasculature may explain the widespread nature of the disease. Heparan sulfate is important for the glomerular endothelial cell and basement membrane charge densities, the anticoagulant......Insulin-dependent diabetic patients with increased urinary albumin excretion are characterized by elevated blood pressure and declining kidney function. In addition, such patients have a high risk of atherosclerotic vascular disease, proliferative retinopathy, and cardiomyopathy, suggesting...

  2. Juvenile nephropathy in a Boxer dog resembling the human nephronophthisis-medullary cystic kidney disease complex.

    Science.gov (United States)

    Basile, Angelo; Onetti-Muda, Andrea; Giannakakis, Konstantinos; Faraggiana, Tullio; Aresu, Luca

    2011-12-01

    A juvenile nephropathy in a 4-year-old male Boxer dog, closely resembling the Nephronophthisis (NPHP)-Medullary Cystic Kidney Disease Complex (MCKD) in humans is described. Gross examination of the kidneys revealed several multiple cysts at the corticomedullary junction and in the medulla. Histological examination was characterized by a widespread tubular atrophy and dilatation, with a marked thickening of the tubular basement membrane, interstitial lymphocytic infiltration and fibrosis. Ultrastructural studies revealed dilated tubules with irregular basement membrane thickening and splitting. Lectin histochemistry investigation revealed that the cysts originated in the distal convoluted tubule and collecting duct. Having excluded all other known cystic diseases of the kidney, and based on the lectin histochemistry results, the macroscopic and histological findings of our case are highly compatible with a diagnosis of the NPHP-MCKD complex. To our knowledge, this is the first report describing this particular lesion.

  3. Basement Fault Reactivation by Fluid Injection into Sedimentary Reservoirs

    Science.gov (United States)

    Peter, Eichhubl; Fan, Zhiqiang; Zhu, Cheng

    2017-04-01

    Many suspected injection-induced earthquakes occur in crystalline basement rather than in the overlying sedimentary injection reservoir. To address why earthquakes nucleate in the basement rather than the injection layer we investigate the relationship between pore pressure diffusion, rock matrix deformation, and induced fault reactivation through 3D fully coupled poroelastic finite element models. These models simulate the temporal and spatial perturbation of pore pressure and solid stresses within a basement fault that extends into overlying sedimentary layers and that is conductive for flow along the fault but a barrier for flow across. We compare the effects of direct pore pressure communication and indirect poroelastic stress transfer from the injection reservoir to the fault on increasing the Coulomb failure stress that could reactivate the basement fault for normal, reverse, and strike-slip faulting stress regimes. Our numerical results demonstrate that volumetric expansion of the reservoir causes a bending of the fault near the injector and induces shear tractions along the downdip direction of the fault in the basement. These induced shear tractions act to increase the Coulomb failure stress for a normal faulting stress regime, and decrease the Coulomb failure stress for a reverse faulting regime. For a strike-slip faulting stress regime, the induced shear tractions increase the Coulomb failure stress both in the reservoir and basement. The induced normal traction on the fault reduces the Coulomb failure stress in all three tectonic regimes, but is larger in the reservoir than in the basement due to the more pronounced poroelastic effect in the reservoir. As a result, strike-slip stress regimes favor fault reactivation in the basement. Whereas the magnitude of the direct pore pressure increase exceeds the magnitude of induced poroelastic stress change, the poroelastic stress change increases the Coulomb failure stress in the basement fault for the normal

  4. The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease.

    OpenAIRE

    Snow, A. D.; Mar, H.; Nochlin, D.; Kimata, K.; Kato, M; Suzuki, S.; Hassell, J.; Wight, T. N.

    1988-01-01

    Two immunocytochemical probes were used to specifically identify and localize heparan sulphate proteoglycans (HSPGs) in 17 cases of Alzheimer's disease (AD). A monoclonal (HK-102) and an affinity-purified polyclonal antibody, each recognizing specific domains on the protein core of a basement membrane-derived HSPG, localized HSPGs to the amyloid fibrils present in neuritic plaques (NPs) and congophilic angiopathy (CA) in the brains of Alzheimer's patients, with weak to no immunostaining in ne...

  5. Linear IgA dermatosis, coeliac disease, and extraintestinal B cell lymphoma.

    OpenAIRE

    Kapur, A.; Isaacs, P E; Kelsey, P R

    1995-01-01

    Linear IgA dermatosis is a malignancy associated rare bullous disorder similar to dermatitis herpetiformis. Linear IgA dermatosis differs from dermatitis herpetiformis in that the IgA deposits in the epidermal basement membrane are linear rather than granular. A patient is presented with coeliac disease who presented with linear IgA dermatosis and anaemia caused by chronic low grade B cell lymphoma.

  6. Meningococcal Outer Membrane Protein NhhA Is Essential for Colonization and Disease by Preventing Phagocytosis and Complement Attack▿

    OpenAIRE

    Sjölinder, Hong; Eriksson, Jens; Maudsdotter, Lisa; Aro, Helena; Jonsson, Ann-Beth

    2008-01-01

    Neisseria meningitidis is a leading cause of meningitis and septicemia worldwide, with a rapid onset of disease and a high morbidity and mortality. NhhA is a meningococcal outer membrane protein included in the family of trimeric autotransporter adhesins. The protein binds to the extracellular matrix proteins heparan sulfate and laminin and facilitates attachment to host epithelial cells. In this study, we show that NhhA is essential for bacterial colonization of the nasopharyngeal mucosa in ...

  7. MEMBRANE BILE ACID RECEPTOR TGR5 - A NEW TARGET IN THE STUDY OF METABOLIC, INFLAMMATORY AND NEOPLASTIC DISEASES

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2016-01-01

    Full Text Available TGR5 are G-protein-linked, membrane bile acids receptors that widely express in tissues of animals and humans. Namely tissue localization of TGR5 determines biological effects of activation of these receptors. This review focuses on the role of TGR5 as a new pharmacological target for the treatment of patients with metabolic syndrome, diabetes, obesity, atherosclerosis, liver disease and cancer processes.

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

    Directory of Open Access Journals (Sweden)

    Ulybin Aleksey

    2016-01-01

    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.

  9. Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

    Science.gov (United States)

    Pérez-Cañamás, A; Benvegnù, S; Rueda, C B; Rábano, A; Satrústegui, J; Ledesma, M D

    2017-05-01

    Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient. Impaired activity of the plasma membrane calcium ATPase (PMCA) increases intracellular calcium. SM induces PMCA decreased activity, which causes oxidative stress. Incubating ASMko-cultured neurons in the histone deacetylase inhibitor, SAHA, restores PMCA activity and calcium homeostasis and, consequently, reduces the increased levels of oxidative stress. No recovery occurs when PMCA activity is pharmacologically impaired or genetically inhibited in vitro. Oral administration of SAHA prevents oxidative stress and neurodegeneration, and improves behavioral performance in ASMko mice. These results demonstrate a critical role for plasma membrane SM in neuronal calcium regulation. Thus, we identify changes in PMCA-triggered calcium homeostasis as an upstream mediator for NPA pathology. These findings can stimulate new approaches for pharmacological remediation in a disease with no current clinical treatments.

  10. Involvement of plasma membrane peroxidases and oxylipin pathway in the recovery from phytoplasma disease in apple (Malus domestica).

    Science.gov (United States)

    Patui, Sonia; Bertolini, Alberto; Clincon, Luisa; Ermacora, Paolo; Braidot, Enrico; Vianello, Angelo; Zancani, Marco

    2013-06-01

    Apple trees (Malus domestica Borkh.) may be affected by apple proliferation (AP), caused by 'Candidatus Phytoplasma mali'. Some plants can spontaneously recover from the disease, which implies the disappearance of symptoms through a phenomenon known as recovery. In this article it is shown that NAD(P)H peroxidases of leaf plasma membrane-enriched fractions exhibited a higher activity in samples from both AP-diseased and recovered plants. In addition, an increase in endogenous SA was characteristic of the symptomatic plants, since its content increased in samples obtained from diseased apple trees. In agreement, phenylalanine ammonia lyase (PAL) activity, a key enzyme of the phenylpropanoid pathway, was increased too. Jasmonic acid (JA) increased only during recovery, in a phase subsequent to the pathological state, and in concomitance to a decline of salicylic acid (SA). Oxylipin pathway, responsible for JA synthesis, was not induced during the development of AP-disease, but it appeared to be stimulated when the recovery occurred. Accordingly, lipoxygenase (LOX) activity, detected in plasma membrane-enriched fractions, showed an increase in apple leaves obtained from recovered plants. This enhancement was paralleled by an increase of hydroperoxide lyase (HPL) activity, detected in leaf microsomes, albeit the latter enzyme was activated in either the disease or recovery conditions. Hence, a reciprocal antagonism between SA- and JA-pathways could be suggested as an effective mechanism by which apple plants react to phytoplasma invasions, thereby providing a suitable defense response leading to the establishment of the recovery phenomenon. Copyright © Physiologia Plantarum 2012.

  11. Basement structure of the Granada basin, Betic Cordilleras, southern Spain

    Science.gov (United States)

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

    1990-06-01

    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.

  12. Phospholipases A2 and neural membrane dynamics: Implications for Alzheimer's disease

    OpenAIRE

    Lee, James C-M.; Simonyi, Agnes; Albert Y Sun; Sun, Grace Y.

    2011-01-01

    Phospholipases A2 (PLA2s) are essential enzymes in cells. They are not only responsible for maintaining the structural organization of cell membranes, but also play a pivotal role in the regulation of cell functions. Activation of PLA2s results in the release of fatty acids and lysophospholipids, products that are lipid mediators and compounds capable of altering membrane microdomains and physical properties. Although not fully understood, recent studies have linked aberrant PLA2 activity to ...

  13. PrPSc accumulation in neuronal plasma membranes links Notch-1 activation to dendritic degeneration in prion diseases

    Directory of Open Access Journals (Sweden)

    DeArmond Stephen J

    2010-01-01

    Full Text Available Abstract Prion diseases are disorders of protein conformation in which PrPC, the normal cellular conformer, is converted to an abnormal, protease-resistant conformer rPrPSc. Approximately 80% of rPrPSc accumulates in neuronal plasma membranes where it changes their physical properties and profoundly affects membrane functions. In this review we explain how rPrPSc is transported along axons to presynaptic boutons and how we envision the conversion of PrPC to rPrPSc in the postsynaptic membrane. This information is a prerequisite to the second half of this review in which we present evidence that rPrPSc accumulation in synaptic regions links Notch-1 signaling with the dendritic degeneration. The hypothesis that the Notch-1 intracellular domain, NICD, is involved in prion disease was tested by treating prion-infected mice with the γ-secretase inhibitor (GSI LY411575, with quinacrine (Qa, and with the combination of GSI + Qa. Surprisingly, treatment with GSI alone markedly decreased NICD but did not prevent dendritic degeneration. Qa alone produced near normal dendritic trees. The combined GSI + Qa treatment resulted in a richer dendritic tree than in controls. We speculate that treatment with GSI alone inhibited both stimulators and inhibitors of dendritic growth. With the combined GSI + Qa treatment, Qa modulated the effect of GSI perhaps by destabilizing membrane rafts. GSI + Qa decreased PrPSc in the neocortex and the hippocampus by 95%, but only by 50% in the thalamus where disease was begun by intrathalamic inoculation of prions. The results of this study indicate that GSI + Qa work synergistically to prevent dendrite degeneration and to block formation of PrPSc.

  14. Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring.

    Directory of Open Access Journals (Sweden)

    Bruce Chesebro

    2010-03-01

    Full Text Available Prion diseases are fatal neurodegenerative diseases of humans and animals characterized by gray matter spongiosis and accumulation of aggregated, misfolded, protease-resistant prion protein (PrPres. PrPres can be deposited in brain in an amyloid-form and/or non-amyloid form, and is derived from host-encoded protease-sensitive PrP (PrPsen, a protein normally anchored to the plasma membrane by glycosylphosphatidylinositol (GPI. Previously, using heterozygous transgenic mice expressing only anchorless PrP, we found that PrP anchoring to the cell membrane was required for typical clinical scrapie. However, in the present experiments, using homozygous transgenic mice expressing two-fold more anchorless PrP, scrapie infection induced a new fatal disease with unique clinical signs and altered neuropathology, compared to non-transgenic mice expressing only anchored PrP. Brain tissue of transgenic mice had high amounts of infectivity, and histopathology showed dense amyloid PrPres plaque deposits without gray matter spongiosis. In contrast, infected non-transgenic mice had diffuse non-amyloid PrPres deposits with significant gray matter spongiosis. Brain graft studies suggested that anchored PrPsen expression was required for gray matter spongiosis during prion infection. Furthermore, electron and light microscopic studies in infected transgenic mice demonstrated several pathogenic processes not seen in typical prion disease, including cerebral amyloid angiopathy and ultrastructural alterations in perivascular neuropil. These findings were similar to certain human familial prion diseases as well as to non-prion human neurodegenerative diseases, such as Alzheimer's disease.

  15. Combination treatment of low fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane secondary to angioid streaks in Paget′s disease - 12 month results

    Directory of Open Access Journals (Sweden)

    Varsha V Prabhu

    2011-01-01

    Full Text Available Angioid streaks also called Knapp striae are small breaks in the Bruch′s membrane and have been reported with a host of systemic diseases. Rupture of streaks or development of secondary choroidal neovascular membrane (CNVM carries a dismal visual prognosis. We report the successful treatment of CNVM secondary to Paget′s disease using low fluence photodynamic therapy (PDT and intravitreal ranibizumab.

  16. The change of serum leptin and its relationship with platelet membrane glycoprotein Ib in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    XIA Dasheng; SONG Yanqiu; LI Chao; ZHANG Feng; WEI Minxin

    2007-01-01

    The aim of this paper was to investigate the change of serum leptin and its relationship with platelet membrane glycoprotein lb(GP Ib)in patients with coronary heart disease(CHD).The enrolled included 50 patients with CHD (CHD group)and 30 patients without CHD(control group)who were diagnosed by coronary angiography.The positive percentage and the average fluorescence intensity of platelet membrane GP Ib were detected by full-blood flow cytometry.Serum leptin was detected by enzyme linked immunosorbent assay.The positive percentage and the average fluorescence intensity of platetet membrane GP Ib in the CHD group were significantly lower than those in the control group (P<0.05).After correcting the differences of systolic blood pressure,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol (HDL-C),fasting glucose,PPBS,fasting insulin and quantita tive insulin sensitive index,serum leptin level in the CHD group was significantly higher than that in the control group (P<0.05).Single factor correlative analysis revealed that serum leptin in CHD patients was negatively correlated with the average fluorescence intensity of platelet membrane GP Ib(P<0.05).Multifactorial stepwise regression analysis showed that serum leptin in CHD patients was independently negatively correlated with the average fluorescence intensity of platelet membrane GP Ib(P<0.05).Logistic analysis demonstrated that serum leptin was independently correlated with the risk of CHD(P<0.05).Hyperleptinemia was veri fied in CHD patients.The increase of serum leptin could affect blood platelet activation.Hyperleptinemia may play an important role in the pathogenesis of CHD.

  17. Basement configuration of KG offshore basin from magnetic anomalies

    Digital Repository Service at National Institute of Oceanography (India)

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

    T dipping at 53◦. This interpretation 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. This is consistent with the known data for the depth to the acous- tic...

  18. De novo glomerular diseases after renal transplantation.

    Science.gov (United States)

    Ponticelli, Claudio; Moroni, Gabriella; Glassock, Richard J

    2014-08-07

    Glomerular diseases developing in the kidney allograft are more often recurrences of the original disease affecting the native kidneys. However, in an undefined number of cases de novo, glomerular diseases unrelated to the original disease in the native kidneys can develop in the transplanted kidney. The clinical presentation and histologic features of de novo diseases are often similar to those features observed in patients with primary or secondary GN in the native kidneys. However, in transplanted kidneys, the glomerular, vascular, and tubulointerstitial changes are often intertwined with structural abnormalities already present at the time of transplant or caused by antibody- or cell-mediated allograft rejection, immunosuppressive drugs, or superimposed infection (most often of a viral nature). The pathophysiology of de novo glomerular diseases is quite variable. In rare cases of de novo minimal change disease, circulating factors increasing the glomerular permeability likely participate. Maladaptive hemodynamic changes and tissue fibrosis caused by calcineurin inhibitors or other factors may be involved in the pathogenesis of de novo FSGS. The exposure of cryptic podocyte antigens may favor the development of de novo membranous nephropathy. Many cases of de novo membranoproliferative GN are related to hepatitis C virus infection. Patients with Alport syndrome lacking antigenic epitopes in their glomerular basement membrane may develop antibodies against these glomerular basement membrane antigens expressed in the transplanted kidney. Infection may cause acute GN to have a heterogeneous clinical presentation and outcome. De novo pauci-immune GN in renal transplant is rare. Preexisting or acquired intolerance to glucose may, in the long term, cause diabetic nephropathy. The prognosis of de novo diseases depends on the type of GN, the severity of lesions caused by the alloimmune response, or the efficacy of immunosuppressive therapy. In most cases, the management

  19. Dense deposit disease in a child with febrile sore throat

    Directory of Open Access Journals (Sweden)

    Giovanni Conti

    2017-01-01

    Full Text Available Dense deposit disease or membranoproliferative glomerulonephritis type II is a rare glomerulopathy characterized on renal biopsy by deposition of abnormal electron-dense material in the glomerular basement membrane. The pathophysiologic basis is uncontrolled systemic activation of the alternate pathway of the complement cascade. C3 nephritic factor, an autoantibody directed against the C3 convertase of the alternate pathway, plays a key role. In some patients, complement gene mutations have been identified. We report the case of a child who had persistent microscopic hematuria, proteinuria, and hypocomplementemia C3 for over 2 months. Renal biopsy confirmed the diagnosis of dense deposit disease.

  20. Mitochondria-Associated Membranes (MAMs): Overview and Its Role in Parkinson's Disease

    NARCIS (Netherlands)

    Rodríguez-Arribas, M; Yakhine-Diop, S M S; Pedro, J M Bravo-San; Gómez-Suaga, P; Gómez-Sánchez, R; Martínez-Chacón, G; Fuentes, J M; González-Polo, R A; Niso-Santano, M

    2016-01-01

    Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by PARK genes and some of n

  1. 新生儿肺透明膜病的护理%Nursing care for neonates with hyaline membrane disease

    Institute of Scientific and Technical Information of China (English)

    黎婷; 彭间英; 罗冰贤

    2013-01-01

    目的 总结讨论新生儿肺透明膜病的护理体会,加强护理意识与方法.方法 对我院收治的82例新生儿肺透明膜病患儿进行系统的回顾性分析,对其护理方法进行总结.结果 经过采取综合护理后大部分患儿康复出院,少数患儿发生并发症,其中4例因肺出血合并弥漫性血管内凝血(DIC)死亡.结论 在积极治疗新生儿肺透明膜病的过程中,采取行之有效的综合护理可显著降低其病死率,提高生存率.%Objective To summarize the nursing experience on neonates with hyaline membrane disease,and to strengthen nursing consciousness and measures.Methods The data on 82 neonates with hyaline membrane disease who had been treated in our hospital were retrospectively analyzed.The nursing methods were summarized.Results After receiving comprehensive nursing care,most of the infants were discharged with rehabilitation.Complications occurred in a few of patients,4 of whom were dead due to pulmonary hemorrhage complicated by disseminated intravascular coagulation (DIC).Conclusions Effective nursing care can significantly reduce the mortality rate and improve the survival rate in the treatment of neonates with hyaline membrane disease.

  2. [A case of membranous nephropathy with ANCA-associated necrotizing glomerulonephritis during oral administration of PTU for Graves' disease].

    Science.gov (United States)

    Fujii, Takayuki; Kawamata, Toyotaka; Ueda, Shiro; Akikusa, Bunshiro; Hasegawa, Shigeru; Tsukahara, Tsunemichi; Iesato, Kenji; Ogawa, Makoto; Saisho, Hiromitsu

    2003-01-01

    We experienced a coincidental case of two types of glomerulopathy associated with Graves' disease. A 64-year-old man, who had been treated with propylthiouracil(PTU) for Graves' disease for 15 years, was admitted to our hospital for macroscopic hematuria and rapidly progressive deterioration of renal function. Although his thyroid function had been within the normal range during treatment, the level of thyrotropin receptor antibody(TRAb) gradually increased from a year before admission. Serological tests revealed that he was positive for myeloperoxidase-antineutrophil cytoplasmic antibody(MPO-ANCA). The renal biopsy specimen showed necrotizing and crescentic glomerulonephritis(GN) superimposed on membranous nephropathy(MN). This is a rare case of MN complicated with ANCA associated crescentic GN in a Graves' disease patient. Association of these two renal alterations was not clearly defined. MN involved with Graves' disease also has been rarely reported. Some reports demonstrated deposition of thyroglobulin and other thyroid related antigens in the glomeruli. In the present case, long-term impairment of Graves' disease and elevation of TRAb might have been responsible for the formation and deposition of thyroid-associated immune complex in the glomeruli. As for crescentic GN, PTU might have induced ANCA-associated GN independently of MN. This case is instructive for considering the relation between Graves' disease and renal injury.

  3. Vancomycin-associated linear IgA disease mimicking toxic epidermal necrolysis*

    Science.gov (United States)

    Pereira, Amanda Regio; de Moura, Luis Henrique Barbizan; Pinheiro, Jhonatan Rafael Siqueira; Pasin, Victor Pavan; Enokihara, Milvia Maria Simões e Silva; Porro, Adriana Maria

    2016-01-01

    Linear IgA dermatosis is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. In the last three decades, many different drugs have been associated with the drug-induced form of the disease, especially vancomycin. We report a case of vancomycin-induced linear IgA disease mimicking toxic epidermal necrolysis. The aim of this work is to emphasize the need to include this differential diagnosis in cases of epidermal detachment and to review the literature on the subject and this specific clinical presentation. PMID:28300888

  4. 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.

    deeper basement was observed throughout. Horst and graben basement structure inferred from our studies can be spatially correlated to the basement structure obtained from Deep Seismic Sounding (DSS) studies13 on the adjacent coastal region. Shallow... in the Mahanadi delta area, India from deep seismic soundings, J Geol Soc India, 29(1987)293-308. ...

  5. Membranous nephropathy in autologous hematopoietic stem cell transplant: autologous graft-versus-host disease or autoimmunity induction?

    Science.gov (United States)

    Abudayyeh, Ala; Truong, Luan D.; Beck, Laurence H.; Weber, Donna M.; Rezvani, Katy; Abdelrahim, Maen

    2015-01-01

    With the increasing utility of hematopoietic stem cell transplantation (SCT) as a treatment for cancer and noncancerous disorders, more challenges and complications associated with SCT have emerged. Renal injury immediately after transplant is common and well understood, but long-term renal injury is becoming more evident. Chronic graft-versus-host disease (GVHD) is a known long-term complication of SCT, and membranous nephropathy (MN) is emerging as the most common cause of SCT-associated glomerular pathology. In this case report, we present a patient who developed features of anti-PLA2R antibody-negative MN following autologous SCT. The renal injury responded well to steroids and further response to rituximab therapy was noted, suggesting antibody-mediated autoimmune glomerular disease. We also present a review of the literature on autologous GVHD and the role of T and B cells in induction of autoimmunity by SCT. PMID:26251713

  6. Importance of pH Homeostasis in Metabolic Health and Diseases: Crucial Role of Membrane Proton Transport

    Directory of Open Access Journals (Sweden)

    Wataru Aoi

    2014-01-01

    Full Text Available Protons dissociated from organic acids in cells are partly buffered. If not, they are transported to the extracellular fluid through the plasma membrane and buffered in circulation or excreted in urine and expiration gas. Several transporters including monocarboxylate transporters and Na+/H+ exchanger play an important role in uptake and output of protons across plasma membranes in cells of metabolic tissues including skeletal muscle and the liver. They also contribute to maintenance of the physiological pH of body fluid. Therefore, impairment of these transporters causes dysfunction of cells, diseases, and a decrease in physical performance associated with abnormal pH. Additionally, it is known that fluid pH in the interstitial space of metabolic tissues is easily changed due to little pH buffering capacitance in interstitial fluids and a reduction in the interstitial fluid pH may mediate the onset of insulin resistance unlike blood containing pH buffers such as Hb (hemoglobin and albumin. In contrast, habitual exercise and dietary intervention regulate expression/activity of transporters and maintain body fluid pH, which could partly explain the positive effect of healthy lifestyle on disease prognosis.

  7. Basement configuration of KG offshore basin from magnetic anomalies

    Indian Academy of Sciences (India)

    V Subrahmanyam; K V Swamy; Neetha Raj

    2016-04-01

    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.

  8. Immunoadsorption in Autoimmune Diseases Affecting the Kidney.

    Science.gov (United States)

    Stummvoll, Georg; Aringer, Martin; Handisurya, Ammon; Derfler, Kurt

    2017-09-01

    Autoantibodies play an important role in the pathophysiology of renal involvement in systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic vasculitis, and anti-glomerular basement membrane disease (or Goodpasture syndrome). Direct removal of autoantibodies therefore has been tried in various ways, first by plasma exchange. Today, immunoadsorption is the extracorporeal method that most effectively removes (pathogenic) immune complexes and antibodies. Although past data have shown efficacy and biocompatibility of immunoadsorption in (renal) SLE, it is still an experimental and expensive procedure, and evidence from randomized controlled trials is needed. Nevertheless, immunoadsorption is being used as a rescue therapy in life-threatening situations of SLE patients because of its fast mode of action and its acceptable safety profile. In granulomatosis with polyangiitis (GPA) (or Wegener's granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane disease, the current standard is plasma exchange. Immunoadsorption, which probably would reduce the autoantibody burden more effectively, might be an even better more effective option, but sufficient evidence is lacking. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Dismenorreia membranosa: uma doença esquecida Membranous dysmenorrhea: a forgotten disease

    Directory of Open Access Journals (Sweden)

    Patrícia Pereira de Oliveira

    2009-06-01

    Full Text Available OBJETIVO: apresentar uma série de casos de dismenorreia membranosa. MÉTODOS: todas as pacientes foram selecionadas a partir da suspeição diagnóstica, após atendimento clínico em consultório privado por relato de dismenorreia dolorosa associada à eliminação espontânea de material elástico com formato semelhante a útero. Apenas fatos relevantes foram descritos do quadro álgico, história médica atual e pregressa e hábitos de vida. O material eliminado foi encaminhado para laboratório de patologia no qual ocorreu a análise macro e microscópica. Os casos em que não se pode provar a eliminação de material com característica membranácea não foram selecionados. Após a confirmação diagnóstica, realizou-se uma revisão da literatura até o ano de 2008 utilizando o método MeSH com o termo "membranous dysmenorrhea". RESULTADOS: três casos clínicos de dismenorreia foram transcritos. Todos os casos, além do quadro característico de dor e eliminação vaginal de material elástico, foram associados ao uso de métodos anticoncepcionais hormonais. CONCLUSÕES: embora haja apenas escassos relatos de caso de dismenorreia membranosa na literatura científica, sua etiologia deve ser suspeita em casos de dor associada a sangramento vaginal com eliminação de material elástico ou firme. O diagnóstico final é dependente do exame anatomopatológico que nunca deve ser dispensado. Observamos necessidade de mais discussões sobre esta patologia com o objetivo de manter o profissional atualizado para exercer diagnóstico e terapêutica adequados.PURPOSE: to present a series of cases of membranous dysmenorrhea. METHODS: all the patients selected were under diagnostic suspicion, after being clinically attended in a private medical office due to the report of painful dysmenorrhea associated with spontaneous elimination of elastic material with uterine shape. Only relevant facts about the pain condition have been described, together with

  10. Analisis Risiko pada Proyek Pembangunan Parkir Basement Jalan Sulawesi Denpasar

    Directory of Open Access Journals (Sweden)

    I Wayan Muka

    2015-04-01

    Full Text Available Construction of Basement Parking Sulawesi Road Denpasar is a government attempt to tackle congestion and parking problems in the city of Denpasar. This activity is highly correlated with the location of Badung Market. This study aims to identify risks arising, assess the level of acceptance of risk analysis, risk mitigation and ownership of dominant risk. The results showed 25 risks identified. Of the risks identified are 24 risk dominant with 5 risk category is unacceptable occurrence of accidents in the project, the landslide during basement excavation, the lack of security fence project that can cause accidents especially hazard fell during basement excavation, the damage caused by natural disasters and the workers were not using safety equipment. Additionally identified 19 risk category is undesirable, one acceptable risk category. Dominant risk is unacceptable risks do 11 mitigation measures such as building damage due to natural disasters (force majeure, which is also a risk with follow-up by reducing the risk that anticipated early preparing for disasters and transfer risk to another party by insuring the work to others. Ownership is the most dominant risk of the contractor. The parties should consider the risks unacceptable category and also should pay attention to the risks classified as undesirable.

  11. Effects of Basement, Structure, and Stratigraphic Heritages on Volcano Behavior

    Science.gov (United States)

    Lagmay, Alfredo Mahar Francisco A.

    2006-06-01

    Effective natural hazard mitigation requires that the science surrounding geophysical events be thoroughly explored. With millions of people living on the flanks of volcanoes, understanding the parameters that effect volcanic behavior is critically important. In particular, basements can influence the occurrence of volcanic eruptions and landslides. This control by the substrate on volcano behavior usually has been considered questionable or less important than the conditions of the deep magma source. However, due to recent findings, this view is changing, specifically with regard to approaches in assessing volcanic hazards. The November 2005 AGU Chapman Conference ``Effects of Basement, Structure, and Stratigraphic Heritages on Volcano Behavior'' brought together geologists and geophysicists from North and South America, Europe, and Asia to discuss the results of their research on the reciprocal effects of the interaction between volcanos and their basements. The conference also highlighted the importance of holding Chapman conferences in developing countries such as the Philippines because many hazardous volcanos are situated in these countries. Apart from having natural field laboratories, these are the very same places that need to promote scientific discourse on volcano research, which can lead to more effective hazard mitigation programs.

  12. The Grenville-age basement of the Andes

    Science.gov (United States)

    Ramos, Victor A.

    2010-01-01

    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.

  13. Lipid composition of membrane rafts, isolated with and without detergent, from the spleen of a mouse model of Gaucher disease.

    Science.gov (United States)

    Hattersley, Kathryn J; Hein, Leanne K; Fuller, Maria

    2013-12-01

    Biological membranes are composed of functionally relevant liquid-ordered and liquid-disordered domains that coexist. Within the liquid-ordered domains are low-density microdomains known as rafts with a unique lipid composition that is crucial for their structure and function. Lipid raft composition is altered in sphingolipid storage disorders, and here we determined the lipid composition using a detergent and detergent-free method in spleen tissue, the primary site of pathology, in a mouse model of the sphingolipid storage disorder, Gaucher disease. The accumulating lipid, glucosylceramide, was 30- and 50-fold elevated in the rafts with the detergent and detergent-free method, respectively. Secondary accumulation of di- and trihexosylceramide resided primarily in the rafts with both methods. The phospholipids distributed differently with more than half residing in the rafts with the detergent-free method and less than 10% with the detergent method, with the exception of the fully saturated species that were primarily in the rafts. Individual isoforms of sphingomyelin correlated with detergent-free extraction and more than half resided in the raft fractions. However, this correlation was not seen with the detergent extraction method as sphingomyelin species were spread across both the raft and non-raft domains. Therefore caution must be exercised when interpreting phospholipid distribution in raft domains as it differs considerably depending on the method of isolation. Importantly, both methods revealed the same lipid alterations in the raft domains in the spleen of the Gaucher disease mouse model highlighting that either method is appropriate to determine membrane lipid changes in the diseased state.

  14. Drug induced linear IgA disease with unusual features: Koebner phenomenon, local insulin sensitivity and annular blister of the nipples.

    Science.gov (United States)

    Rashid Dar, Nasser; Raza, Naeem

    2008-01-01

    Linear IgA disease is an autoimmune subepidermal bullous disease in which linear IgA deposits are found at the basement membrane zone. It is classically idiopathic but may be drug induced. We report on a patient with drug induced linear IgA disease who exhibited certain unusual and interesting clinical features including isomorphic Koebner response, annular blister of the nipples and local insulin sensitivity. To the best of our knowledge, these clinical features have not yet been reported in linear IgA disease.

  15. 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

    1992-01-01

    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...

  16. [ANALYSIS OF ARACHIDONIC ACID RELATIVE CONTENT CHANGES IN ERYTHROCYTES AND PLATELETS PHOSPHOLIPIDS MEMBRANES FEATURES IN CORONARY HEART DISEASE WITH ATRIAL FIBRILLATION PATIENTS].

    Science.gov (United States)

    Lizogub, V G; Zavalska, T V; Merkulova, I O; Bryuzgina, T S

    2015-01-01

    Erythrocytes and platelets phospholipid membranes fatty acid spectrum was detected in coronary heart disease and atrial fibrillation patients and in patients with coronary heart disease without atrial fibrillation. 87 patients were investigated. Significant decrease in the arachidonic acid relative content in coronary heart disease patients compared with healthy individuals was related. As well as a significant decrease in the arachidonic acid relative content in coronary heart disease and atrial fibrillation patients compared with coronary heart disease patients without atrial fibrillation was related too. These dates may indicate that decreasing relative content arachidonic acid can be possible pathogenetic link in the development of arrhythmias.

  17. Pathophysiological advances in membranous nephropathy: time for a shift in patient's care.

    Science.gov (United States)

    Ronco, Pierre; Debiec, Hanna

    2015-05-16

    Membranous nephropathy is a major cause of nephrotic syndrome of non-diabetic origin in adults. It is the second or third leading cause of end-stage renal disease in patients with primary glomerulonephritis, and is the leading glomerulopathy that recurs after kidney transplantation (occurring in about 40% of patients). Treatment with costly and potentially toxic drugs remains controversial and challenging, partly because of insufficient insight into the pathogenesis of the disease and absence of sensitive biomarkers of disease activity. The disease is caused by the formation of immune deposits on the outer aspect of the glomerular basement membrane, which contain podocyte or planted antigens and circulating antibodies specific to those antigens, resulting in complement activation. In 2002, podocyte neutral endopeptidase was identified as an antigenic target of circulating antibodies in alloimmune neonatal nephropathy, and in 2009, podocyte phospholipase A2 receptor (PLA2R) was reported as an antigenic target in autoimmune adult membranous nephropathy. These major breakthroughs were translated to clinical practice very quickly. Measurement of anti-PLA2R antibodies in serum and detection of PLA2R antigen in glomerular deposits can now be done routinely. Anti-PLA2R antibodies have high specificity (close to 100%), sensitivity (70-80%), and predictive value. PLA2R detection in immune deposits allows for retrospective diagnosis of PLA2R-related membranous nephropathy in archival kidney biopsies. These tests already have a major effect on diagnosis and monitoring of treatment, including after transplantation.

  18. Secreted and membrane-bound mucins and idiopathic peptic ulcer disease.

    Science.gov (United States)

    Niv, Yaron; Boltin, Doron

    2012-01-01

    The incidence of Helicobacter pylori and non-steroidal anti-inflammatory drug (NSAID)-negative peptic ulcer disease has increased over the last two decades, especially in the Western world and in countries with low H. pylori infection rates. Idiopathic peptic ulcer disease is a recently described entity which relates to peptic ulcers not caused by H. pylori, NSAID/aspirin therapy, other ulcerogenic organisms and drugs, or other rare malignant and benign diseases. Structural and secreted mucins create the unstirred gastric mucus layer and maintain a stable pH above the gastric mucosa. This mucous layer prevents enzymatic attack by acid and pepsin. Inhibition of cyclooxygenase by NSAID and aspirin inhibits prostaglandin production, inhibits mucin and bicarbonate secretion, and exposes the mucosa to the toxic effects of acid and intragastric enzymes. There is also a complex relationship between H. pylori and different mucin subtypes which on one hand facilitates mucin invasion but on the other hand protects the gastric mucosa. Genetic and epigenetic changes in the mucin molecule may be responsible for idiopathic peptic ulcer disease, but this hypothesis must be further investigated. Herein, the mucin hypothesis of idiopathic peptic ulcer disease is explored.

  19. Human Amnion Membrane Serves as a Substratum for Growing Axons in vitro and in vivo

    Science.gov (United States)

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

    1987-05-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    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.

  1. Formation and Evolution of the Junggar basin basement

    Science.gov (United States)

    He, D.

    2015-12-01

    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

  2. Heterogeneous disease: a child case of lichen planus pemphigoides triggered by varicella.

    Science.gov (United States)

    İlknur, Turna; Akarsu, Sevgi; Uzun, Soner; Özer, Erdener; Fetil, Emel

    2011-07-01

    Lichen planus pemphigoides (LPP) is a rare and controversial disease. It is characterized clinically by tense bullae arising both on lichen planus papules and on uninvolved skin, histologically by the demonstration of subepidermal bullae and by linear deposits of immunoglobulin G and C3 along the basement membrane zone on immunofluorescence of peribullous skin. Some authors consider LPP as the combination of lichen planus and bullous pemphigoid. Others think that it most likely encompasses a heterogeneous group of subepidermal autoimmune blistering disorders occurring in association with lichen planus. We present a child case that supports the heterogeneous condition of this disease triggered by varicella.

  3. Podocyturia: A Clue for the Rational Use of Amiloride in Alport Renal Disease

    Directory of Open Access Journals (Sweden)

    H. Trimarchi

    2016-01-01

    Full Text Available No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment. Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. However, as any hereditary disease, it is expressed as early as in the intrauterine life, and usually an index case is helpful to detect family-related cases. As no specific treatment exists, pathophysiologically based approaches are useful. The present case illustrates the reduction rate of urinary podocyte loss and proteinuria after amiloride administration and suggests the molecular pathways involved in Alport renal disease. Finally, podocyturia rather than proteinuria should be considered as an earlier biomarker of kidney involvement and disease progression in Alport disease.

  4. Podocyturia: A Clue for the Rational Use of Amiloride in Alport Renal Disease

    Science.gov (United States)

    Trimarchi, H.; Canzonieri, R.; Muryan, A.; Schiel, A.; Araoz, A.; Paulero, M.; Andrews, J.; Rengel, T.; Forrester, M.; Lombi, F.; Pomeranz, V.; Iriarte, R.; Zotta, E.

    2016-01-01

    No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment. Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. However, as any hereditary disease, it is expressed as early as in the intrauterine life, and usually an index case is helpful to detect family-related cases. As no specific treatment exists, pathophysiologically based approaches are useful. The present case illustrates the reduction rate of urinary podocyte loss and proteinuria after amiloride administration and suggests the molecular pathways involved in Alport renal disease. Finally, podocyturia rather than proteinuria should be considered as an earlier biomarker of kidney involvement and disease progression in Alport disease. PMID:26942026

  5. Antimicrobial Peptides: Insights into Membrane Permeabilization, Lipopolysaccharide Fragmentation and Application in Plant Disease Control

    OpenAIRE

    Datta, A.; Ghosh, A; Airoldi, C; Sperandeo, P; Mroue, K; Jimenez-Barbero, J; Kundu, P.; Ramamoorthy, A; Bhunia, A

    2015-01-01

    The recent increase in multidrug resistance against bacterial infections has become a major concern to human health and global food security. Synthetic antimicrobial peptides (AMPs) have recently received substantial attention as potential alternatives to conventional antibiotics because of their potent broad-spectrum antimicrobial activity. These peptides have also been implicated in plant disease control for replacing conventional treatment methods that are polluting and hazardous to the en...

  6. Diagnosis and classification of Goodpasture's disease (anti-GBM).

    Science.gov (United States)

    Hellmark, Thomas; Segelmark, Mårten

    2014-01-01

    Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM autoantibodies. The disease is a prototype of autoimmune disease, where the patients develop autoantibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1(∗)1501 and DRB1(∗)1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV): lessons from past programs and implications for the future.

    Science.gov (United States)

    Holst, Johan; Oster, Philipp; Arnold, Richard; Tatley, Michael V; Næss, Lisbeth M; Aaberge, Ingeborg S; Galloway, Yvonne; McNicholas, Anne; O'Hallahan, Jane; Rosenqvist, Einar; Black, Steven

    2013-06-01

    The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004-2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains.

  8. [Modern ultrasonographic techniques for the study of the synovial membrane in rheumatic diseases].

    Science.gov (United States)

    Jeka, Sławomir; Sokólska, Elzbieta; Ignaczak, Piotr; Dura, Marta

    2010-01-01

    In recent years ultrasonography has become one of basic imaging techniques used by radiologists, orthopedists, and rheumatologists for the study of the musculoskeletal system, particularly in patients with rheumatic diseases. This position of ultrasonography is the result of rapid technical advances. Contemporary ultrasound scanners have little in common with those used when ultrasonography was introduced into medicine. Modern ultrasound scanners offer additional options like tissue harmonic imaging, power color Doppler, volumetric ultrasonography (3D/4D imaging), and contrast-enhanced ultrasonography. Moreover, image resolution during examination has significantly been improved thanks to high-resolution transducers and software for image analysis. This article discusses modern ultrasonographic techniques and their use.

  9. Safety review: two outer membrane vesicle (OMV) vaccines against systemic Neisseria meningitidis serogroup B disease.

    Science.gov (United States)

    Nøkleby, H; Aavitsland, P; O'Hallahan, J; Feiring, B; Tilman, S; Oster, P

    2007-04-20

    MenBvac is an OMV vaccine against systemic serogroup B Neisseria meningitidis disease. MenBvac was developed for control of a B:15:P1.7,16 subtype epidemic in Norway and administered to 180,000 subjects in 28 clinical studies. MeNZB, a daughter vaccine of MenBvac, was developed for a clonal B:4:P1.7b,4 epidemic in New Zealand and administered to 1 million people OMV-based vaccines containing 25 microg antigen can be considered safe for use in all age groups.

  10. Provenance of Neoproterozoic sedimentary basement of northern Iran, Kahar Formation

    Science.gov (United States)

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

    2015-11-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    YAN Xiangbin; LI Tiejun; ZHANG Tao

    2004-01-01

    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.

  12. Erythrocyte membrane proteins and membrane skeleton

    Institute of Scientific and Technical Information of China (English)

    LU Yiqin; LIU Junfan

    2007-01-01

    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.

  13. Discovery of novel DENN proteins: implications for the evolution of eukaryotic intracellular membrane structures and human disease

    Directory of Open Access Journals (Sweden)

    Dapeng eZhang

    2012-12-01

    Full Text Available The tripartite DENN module, comprised of a N-terminal longin domain, followed by DENN and d-DENN domains, is a GDP-GTP exchange factor (GEFs for Rab GTPases, which are regulators of practically all membrane trafficking events in eukaryotes. Using sequence and structure analysis we identify multiple novel homologs of the DENN module, many of which can be traced back to the ancestral eukaryote. These findings provide unexpected leads regarding key cellular processes such as autophagy, vesicle-vacuole interactions, chromosome segregation and human disease. Of these, SMCR8, the folliculin interacting protein-1 and 2 (FNIP1 and FNIP2, nitrogen permease regulator 2 (NPR2 and NPR3 are proposed to function in recruiting Rab GTPases during different steps of autophagy, fusion of autophagosomes with the vacuole and regulation of cellular metabolism. Another novel DENN protein identified in this study is C9ORF72; expansions of the hexanucleotide GGGGCC in its first intron have been recently implicated in amyotrophic lateral sclerosis (ALS and fronto-temporal dementia (FTD. While this mutation is proposed to cause a RNA-level defect, the identification of C9ORF72 as a potential DENN-type GEF raises the possibility that at least part of the pathology might relate to a specific Rab-dependent vesicular trafficking process, as has been observed in the case of some other neurological conditions with similar phenotypes. We present evidence that the longin domain, such as those found in the DENN module, are likely to have been ultimately derived from the related domains found in prokaryotic GTPase-activating proteins of MglA-like GTPases. Thus, the origin of the longin domains from this ancient GTPase-interacting domain, concomitant with the radiation of GTPases, especially of the Rab clade, played an important role in the dynamics of eukaryotic intracellular membrane systems.

  14. Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    A. A. Daak

    2011-01-01

    Full Text Available The cytotoxic compound hydroxyurea (HU is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19 and HU-untreated (n=17 sickle cell patients and controls (n=20. The HU-treated compared with the HU-untreated patients had lower arachidonic (AA acid level in ethanolamine, physphoglycerids (EPG (22.9±1.2   versus   24.0±1.1%,  P<0.05 serine SPG (22.13±2.2   versus   24.9±2.3%,  P<0.01 phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG. In contrast, the untreated group had significantly (P<0.05 lower DHA and total n-3 compared with the controls in EPG (2.7±0.4   versus   3.2±0.6% and 4.6±0.5   versus   5.2±0.7% and CPG (0.7±0.2   versus   1.0±0.2% and 1.2±0.2   versus   1.4±0.3. HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

  15. Plasma membrane proteome analysis of the early effect of alcohol on liver:implications for alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Lijun Zhang; Ye Zheng; Pengyuan Yang; Zhenghong Yuan; Xiaofang Jia; Yanling Feng; Xia Peng; Zhiyong Zhang; Wenjiang Zhou; Zhanqing Zhang; Fang Ma; Xiaohui Liu

    2011-01-01

    In humans, the over-consumption of alcohol can lead to serious liver disease. To examine the early effects of alcohol on liver disease, rats were given sufficient ethanol to develop liver cirrhosis. Rats before the onset of fibrosis were studied in this work. Plasma membranes (PM) of liver were extracted by twice sucrose density gradient centrifugation. The proteome profiles of PM from ethanol-treated rats and the controls were analyzed using two-dimensional gel electrophoresis (2-DE) and isobaric tag for relative and absolute quantitation (iTRAQ) tech-nology. Ethanol treatment altered the amount of 15 differ-ent liver proteins: 10 of them were detected by 2-DE and 5 by iTRAQ. Keratin 8 was detected by both methods.Gene ontology analysis of these differentially detected proteins indicated that most of them were involved in important cell functions such as binding activity (includ-ing ion, DNA, ATP binding, etc.), cell structure, or enzyme activity. Among these, annexin A2, keratin 8, and keratin 18 were further verified using western blot analy-sis and annexin A2 was verified by immunohistochemis-try. Our results suggested that alcohol has the potential to affect cell structure, adhesion and enzyme activity by altering expression levels of several relevant proteins in the PM. To the best of our knowledge, this is the first time to study the effect of alcohol on the liver PM pro-teome and it might be helpful for understanding the poss-ible mechanisms of alcohol-induced liver disease.

  16. Anti-GBM Disease in Pregnancy

    Directory of Open Access Journals (Sweden)

    Mohammed Muqeet Adnan MD

    2015-12-01

    Full Text Available Antiglomerular basement membrane (GBM disease presenting during pregnancy is uncommon. We present a case of a pregnant female who presented with acute renal failure requiring dialysis due to anti-GBM disease. She responded well to plasma exchange, high-dose steroids, and hemodialysis. Cyclophosphamide was discussed but not given at the patient’s request due to concerns for the well-being of the fetus. Unfortunately, she suffered a spontaneous abortion in her eighth week of pregnancy. Subsequently, she had progressive improvement in her renal function and became hemodialysis independent at 2 weeks after diagnosis. Her renal function returned to baseline 3 months after diagnosis. We present this case in detail and review the literature regarding anti-GBM disease in pregnancy.

  17. Effects of phytanic acid on the vitamin E status, lipid composition and physical properties of retinal cell membranes: implications for adult Refsum disease.

    Science.gov (United States)

    Young, S P; Johnson, A W; Muller, D P

    2001-12-01

    Adult Refsum disease is an inherited disorder in which phytanic acid accumulates in tissues and serum. Two hypotheses have been proposed to explain the pathogenesis of this condition. The molecular distortion hypothesis suggests that phytanic acid may alter membrane composition and structure, thereby affecting membrane function(s). The anti-metabolite hypothesis suggests that an accumulation of phytanic acid in membranes may interfere with vitamin E function. These two hypotheses were investigated by studying the effects of modulating phytanic acid and alpha-tocopherol concentrations on the fatty acid composition and certain physical parameters of cultured retinal cells. Results showed that (a) the phospholipid fraction of retinal cells readily incorporated phytanic acid, (b) the incorporation of phytanic acid increased membrane fluidity, (c) there was no competition for uptake between phytanic acid and alpha-tocopherol, and (d) the incorporation of phytanic acid did not increase the susceptibility of membranes to lipid peroxidation in vitro. These results obtained with cultured retinal cells suggest that the molecular distortion hypothesis, but not the anti-metabolite hypothesis, could explain the pathogenesis of adult Refsum disease. In vitro tissue culture models can, however, only approximate to the much more complex situation that occurs in vivo.

  18. Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms.

    Science.gov (United States)

    Nanagara, R; Duray, P H; Schumacher, H R

    1996-10-01

    To perform the first systematic electronmicroscopic (EM) and immunoelectron microscopy (IEM) study of the pathological changes and the evidence of spirochete presence in synovial membranes and synovial fluid (SF) cells of patients with chronic Lyme arthritis. EM examination was performed on four synovial membrane and eight SF cell samples from eight patients with chronic Lyme disease. Spirochetal antigens in the samples were sought by IEM using monoclonal antibody to Borrelia burgdorferi outer surface protein A (OspA) as the immunoprobe. Prominent ultrastructural findings were surface fibrin-like material, thickened synovial lining cell layer and signs of vascular injury. Borrelia-like structures were identified in all four synovial membranes and in two of eight SF cell samples. The presence of spirochetal antigens was confirmed by IEM in all four samples studied (one synovial membrane and three SF cell samples). OspA labelling was in perivascular areas, deep synovial stroma among collagen bundles, and in vacuoles of fibroblasts in synovial membranes; and in cytophagosomes of mononuclear cells in SF cell samples. Electron microscopy adds further evidence for persistence of spirochetal antigens in the joint in chronic Lyme disease. Locations of spirochetes or spirochetal antigens both intracellulary and extracellulary in deep synovial connective tissue as reported here suggest sites at which spirochaetes may elude host immune response and antibiotic treatment.

  19. Structural analysis of a fractured basement reservoir, central Yemen

    Science.gov (United States)

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

    2013-04-01

    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

  20. Gravitational salt tectonics above a rising basement plateau offshore Algeria

    Science.gov (United States)

    Gaullier, Virginie; Vendeville, Bruno C.; Besème, Grégoire; Legoux, Gaetan; Déverchère, Jacques; Lymer, Gaël

    2017-04-01

    Seismic data (survey "MARADJA 1", 2003) offshore the Algerian coast have imaged an unexpected deformation pattern of the Messinian salt (Mobile Unit; MU) and its sedimentary overburden (Messinian Upper Unit and Plio-Quaternary) above an actively rising plateau in the subsalt basement. From a geodynamic point of view, the region is undergoing crustal convergence, as attested by the Boumerdes earthquake (2003, magnitude 6.8). The rise of this plateau, forming a 3D promontory restricted to the area offshore Algiers, is associated with that geodynamic setting. The seismic profiles show several subsalt thrusts (Domzig et al. 2006). The data provided additional information on the deformation of the Messinian mobile evaporitic unit and its Plio-Quaternary overburden. Margin-perpendicular profiles show mostly compressional features (anticlines and synclines) that had little activity during Messinian times, then grew more during Plio-Quaternary times. A few normal faults are also present, but are not accompanied by salt rise. By contrast, margin-parallel profiles clearly show that extensional, reactive salt diapiric ridges (symptomatic with their triangular shape in cross section) formed early, as early as the time of deposition of the Messinian Upper Unit, as recorded by fan-shaped strata. These ridges have recorded E-W, thin-skinned gravity gliding above the Messinian salt, as a response to the rise of the basement plateau. We tested this hypothesis using two analogue models, one where we assumed that the rise of the plateau started after Messinian times (initially tabular salt across the entire region), the second model assumed that the plateau had already risen partially as the Messininan Mobile Unit was deposited (salt initially thinner above the plateau than in the adjacent regions). In both experiments, the rise of the plateau generated preferential E-W extension above the salt, combined with N-S shortening. Extension was caused by gravity gliding of the salt from

  1. Membranes, peptides, and disease: unraveling the mechanisms of viral proteins with solid state nuclear magnetic resonance spectroscopy.

    Science.gov (United States)

    Eddy, Matthew T; Yu, Tsyr-Yan

    2014-01-01

    The interplay between peptides and lipid bilayers drives crucial biological processes. For example, a critical step in the replication cycle of enveloped viruses is the fusion of the viral membrane and host cell endosomal membrane, and these fusion events are controlled by viral fusion peptides. Thus such membrane-interacting peptides are of considerable interest as potential pharmacological targets. Deeper insight is needed into the mechanisms by which fusion peptides and other viral peptides modulate their surrounding membrane environment, and also how the particular membrane environment modulates the structure and activity of these peptides. An important step toward understanding these processes is to characterize the structure of viral peptides in environments that are as biologically relevant as possible. Solid state nuclear magnetic resonance (ssNMR) is uniquely well suited to provide atomic level information on the structure and dynamics of both membrane-associated peptides as well as the lipid bilayer itself; further ssNMR can delineate the contribution of specific membrane components, such as cholesterol, or changing cellular conditions, such as a decrease in pH on membrane-associating peptides. This paper highlights recent advances in the study of three types of membrane associated viral peptides by ssNMR to illustrate the more general power of ssNMR in addressing important biological questions involving membrane proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. ENFORCEMENT OF FINANCIAL BASEMENTS AS A FACTOR OF TERRITORIES DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    E.N. Sidorova

    2007-06-01

    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.

  3. Predicted vs observed effectiveness of outer membrane vesicle (OMV) vaccines against meningococcal serogroup B disease: Systematic review.

    Science.gov (United States)

    Harder, Thomas; Koch, Judith; Wichmann, Ole; Hellenbrand, Wiebke

    2017-08-01

    Human serum bactericidal antibody levels (hSBA) are commonly used as an immune correlate of protection after vaccination against meningococcal disease. We performed a systematic review of how well this marker correlates with protection induced by outer membrane vesicle (OMV) vaccines against meningococcal B (MenB) disease. To compare vaccine effectiveness (VE) of OMV vaccines against MenB predicted by hSBA (predicted protection) to VE from clinical studies (observed protection). Studies identified by searching Medline, Embase, Global Health, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects. Studies reporting hSBA after vaccination with OMV vaccines and subsequent efficacy/effectiveness in a MenB outbreak were included. Data extraction and risk of bias assessments were performed by two independent investigators. Predicted VE and observed VE measured during MenB outbreaks. We included 19 studies (eleven randomized controlled trials, six cohort studies, two case-control studies). Four different OMV vaccines were applied during nine different outbreaks (six countries, 1987-2009). A comparison between predicted and observed VE was possible using results from studies performed during five outbreaks. Predicted VE differed from observed VE by 2-59%, with greater differences observed in younger age groups. In general, predicted VE tended to be lower than observed VE. CONCLUSION AND RELEVANCE: hSBA induced by OMV vaccines correlates moderately well with protection against MenB in older children and adults. The correlation was poor at very young ages, for which low VE was observed. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  4. Phase I Safety and Immunogenicity Study of a Candidate Meningococcal Disease Vaccine Based on Neisseria lactamica Outer Membrane Vesicles▿

    Science.gov (United States)

    Gorringe, Andrew R.; Taylor, Stephen; Brookes, Charlotte; Matheson, Mary; Finney, Michelle; Kerr, Moyra; Hudson, Michael; Findlow, Jamie; Borrow, Ray; Andrews, Nick; Kafatos, George; Evans, Cariad M.; Read, Robert C.

    2009-01-01

    Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal Neisseria species, including Neisseria lactamica. We have previously demonstrated that outer membrane vesicles (OMVs) from N. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an N. lactamica OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup B Neisseria meningitidis, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing ≥4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, this N. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response to N. meningitidis. PMID:19553555

  5. Dietary supplementation with docosahexanoic acid (DHA) increases red blood cell membrane flexibility in mice with sickle cell disease.

    Science.gov (United States)

    Wandersee, Nancy J; Maciaszek, Jamie L; Giger, Katie M; Hanson, Madelyn S; Zheng, Suilan; Guo, YiHe; Mickelson, Barbara; Hillery, Cheryl A; Lykotrafitis, George; Low, Philip S; Hogg, Neil

    2015-02-01

    Humans and mice with sickle cell disease (SCD) have rigid red blood cells (RBCs). Omega-3 fatty acids, such as docosahexanoic acid (DHA), may influence RBC deformability via incorporation into the RBC membrane. In this study, sickle cell (SS) mice were fed natural ingredient rodent diets supplemented with 3% DHA (DHA diet) or a control diet matched in total fat (CTRL diet). After 8weeks of feeding, we examined the RBCs for: 1) stiffness, as measured by atomic force microscopy; 2) deformability, as measured by ektacytometry; and 3) percent irreversibly sickled RBCs on peripheral blood smears. Using atomic force microscopy, it is found that stiffness is increased and deformability decreased in RBCs from SS mice fed CTRL diet compared to wild-type mice. In contrast, RBCs from SS mice fed DHA diet had markedly decreased stiffness and increased deformability compared to RBCs from SS mice fed CTRL diet. Furthermore, examination of peripheral blood smears revealed less irreversibly sickled RBCs in SS mice fed DHA diet as compared to CTRL diet. In summary, our findings indicate that DHA supplementation improves RBC flexibility and reduces irreversibly sickled cells by 40% in SS mice. These results point to potential therapeutic benefits of dietary omega-3 fatty acids in SCD.

  6. Phase I safety and immunogenicity study of a candidate meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.

    Science.gov (United States)

    Gorringe, Andrew R; Taylor, Stephen; Brookes, Charlotte; Matheson, Mary; Finney, Michelle; Kerr, Moyra; Hudson, Michael; Findlow, Jamie; Borrow, Ray; Andrews, Nick; Kafatos, George; Evans, Cariad M; Read, Robert C

    2009-08-01

    Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal Neisseria species, including Neisseria lactamica. We have previously demonstrated that outer membrane vesicles (OMVs) from N. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an N. lactamica OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup B Neisseria meningitidis, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing > or =4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, this N. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response to N. meningitidis.

  7. An outer membrane vesicle vaccine for prevention of serogroup A and W-135 meningococcal disease in the African meningitis belt.

    Science.gov (United States)

    Norheim, G; Tunheim, G; Næss, L M; Kristiansen, P A; Caugant, D A; Rosenqvist, E

    2012-08-01

    The bacterium Neisseria meningitidis of serogroups A and W-135 has in the recent decade caused most of the cases of meningococcal meningitis in the African meningitis belt, and there is currently no efficient and affordable vaccine available demonstrated to protect against both these serogroups. Previously, deoxycholate-extracted outer membrane vesicle (OMV) vaccines against serogroup B meningococci have been shown to be safe and induce protection in humans in clonal outbreaks. The serogroup A and W-135 strains isolated from meningitis belt epidemics demonstrate strikingly limited variation in major surface-exposed protein structures. We have here investigated whether the OMV vaccine strategy also can be applied to prevent both serogroups A and W-135 meningococcal disease. A novel vaccine combining OMV extracted from recent African serogroup A and W-135 strains and adsorbed to aluminium hydroxide was developed and its antigenic characteristics and immunogenicity were studied in mice. The specificity of the antibody responses was analysed by immunoblotting and serum bactericidal activity (SBA) assays. Moreover, the bivalent A+W-135 vaccine was compared with monovalent A and W-135 OMV vaccines. The bivalent OMV vaccine was able to induce similar SBA titres as the monovalent A or W-135 OMV towards both serogroups. High SBA titres were also observed against a meningococcal serogroup C strain. These results show that subcapsular antigens may be of importance when developing broadly protective and affordable vaccines for the meningitis belt. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

  8. Basement structures over Rio Grande Rise from gravity inversion

    Science.gov (United States)

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

    2017-04-01

    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.

  9. FLUORESCENCE OVERLAY ANTIGEN MAPPING OF THE EPIDERMAL BASEMENT-MEMBRANE ZONE .2. COLOR FIDELITY

    NARCIS (Netherlands)

    BRUINS, S; DEJONG, MCJM; HEERES, K; WILKINSON, MHF; JONKMAN, MF; VANDERMEER, JB

    In this second report on the fluorescence overlay antigen mapping (FOAM) technique, we highlight some of the errors that may influence faithful color rendition of slide preparations using triple antigen immunofluorescence staining. Reliable interpretation of multicolor fluorescence images requires

  10. FLUORESCENCE OVERLAY ANTIGEN MAPPING OF THE EPIDERMAL BASEMENT-MEMBRANE ZONE .1. GEOMETRIC ERRORS

    NARCIS (Netherlands)

    BRUINS, S; DEJONG, MCJM; HEERES, K; WILKINSON, MHF; JONKMAN, MF; VANDERMEER, JB

    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

  11. 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

    1989-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Wilhelm eKriz

    2014-12-01

    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.

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

    Science.gov (United States)

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

    2014-01-01

    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.

  14. FLUORESCENCE OVERLAY ANTIGEN MAPPING OF THE EPIDERMAL BASEMENT-MEMBRANE ZONE .1. GEOMETRIC ERRORS

    NARCIS (Netherlands)

    BRUINS, S; DEJONG, MCJM; HEERES, K; WILKINSON, MHF; JONKMAN, MF; VANDERMEER, JB

    1994-01-01

    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

  15. FLUORESCENCE OVERLAY ANTIGEN MAPPING OF THE EPIDERMAL BASEMENT-MEMBRANE ZONE .1. GEOMETRIC ERRORS

    NARCIS (Netherlands)

    BRUINS, S; DEJONG, MCJM; HEERES, K; WILKINSON, MHF; JONKMAN, MF; VANDERMEER, JB

    1994-01-01

    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

  16. Matrigel Basement Membrane Matrix influences expression of microRNAs in cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Price, Karina J. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6008 (Australia); Tsykin, Anna [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Giles, Keith M. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Sladic, Rosemary T. [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); Epis, Michael R. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Ganss, Ruth [Laboratory for Cancer Medicine Angiogenesis Unit, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Goodall, Gregory J. [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Department of Medicine, University of Adelaide, Adelaide, SA 5005 (Australia); Leedman, Peter J., E-mail: peter.leedman@waimr.uwa.edu.au [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6008 (Australia)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Matrigel alters cancer cell line miRNA expression relative to culture on plastic. Black-Right-Pointing-Pointer Many identified Matrigel-regulated miRNAs are implicated in cancer. Black-Right-Pointing-Pointer miR-1290, -210, -32 and -29b represent a Matrigel-induced miRNA signature. Black-Right-Pointing-Pointer miR-32 down-regulates Integrin alpha 5 (ITGA5) mRNA. -- Abstract: Matrigel is a medium rich in extracellular matrix (ECM) components used for three-dimensional cell culture and is known to alter cellular phenotypes and gene expression. microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have roles in cancer. While miRNA profiles of numerous cell lines cultured on plastic have been reported, the influence of Matrigel-based culture on cancer cell miRNA expression is largely unknown. This study investigated the influence of Matrigel on the expression of miRNAs that might facilitate ECM-associated cancer cell growth. We performed miRNA profiling by microarray using two colon cancer cell lines (SW480 and SW620), identifying significant differential expression of miRNAs between cells cultured in Matrigel and on plastic. Many of these miRNAs have previously been implicated in cancer-related processes. A common Matrigel-induced miRNA signature comprised of up-regulated miR-1290 and miR-210 and down-regulated miR-29b and miR-32 was identified using RT-qPCR across five epithelial cancer cell lines (SW480, SW620, HT-29, A549 and MDA-MB-231). Experimental modulation of these miRNAs altered expression of their known target mRNAs involved in cell adhesion, proliferation and invasion, in colon cancer cell lines. Furthermore, ITGA5 was identified as a novel putative target of miR-32 that may facilitate cancer cell interactions with the ECM. We propose that culture of cancer cell lines in Matrigel more accurately recapitulates miRNA expression and function in cancer than culture on plastic and thus is a valuable approach to the in vitro study of miRNAs.

  17. 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

    1985-01-01

    -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...

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

    DEFF Research Database (Denmark)

    Albrechtsen, R; Nielsen, M; Wewer, U

    1981-01-01

    with molecular weights of 400,000 and 200,000 of rat laminin in sodium dodecyl sulfate:polyacrylamide gel electrophoresis. The neoplastic cells in malignant breast tissues showed strong cytoplasmic staining for laminin, and a positive reaction was aslo found in lymph node metastases. In some cases in which only...

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

    DEFF Research Database (Denmark)

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

    1989-01-01

    -[(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...

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

    DEFF Research Database (Denmark)

    He, Xiaowen; Liu, Jie; Qi, Yanmei

    2010-01-01

    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...

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    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...

  2. Basement domain map of the conterminous U.S.A. and Alaska

    Data.gov (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...

  3. Basement domain map of the conterminous U.S.A. and Alaska

    Data.gov (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...

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

    OpenAIRE

    1990-01-01

    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...

  5. Cell proliferation in human epiretinal membranes: characterization of cell types and correlation with disease condition and duration

    OpenAIRE

    Lesnik Oberstein, S.Y.; Byun, J; Herrera, D; Chapin, E.A.; Fisher, S K; Lewis, G.P.

    2011-01-01

    Purpose To quantify the extent of cellular proliferation and immunohistochemically characterize the proliferating cell types in epiretinal membranes (ERMs) from four different conditions: proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, post–retinal detachment, and idiopathic ERM. Methods Forty-six ERMs were removed from patients undergoing vitrectomy and immediately fixed in paraformaldehyde. The membranes were processed whole and immunolabeled with either anti-MIB-...

  6. Diagnosis and treatment of primary glomerular diseases Membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy.

    NARCIS (Netherlands)

    Deegens, J.K.J.; Wetzels, J.F.M.

    2005-01-01

    Membranous nephropathy, focal segmental glomerulosclerosis (FSGS) and IgA nephropathy are the most frequent and important primary glomerulopathies. Idiopathic membranous nephropathy and primary FSGS usually present with a nephrotic syndrome with or without renal insufficiency, whereas IgA nephropath

  7. Anti-GBM disease and renal vein thrombosis.

    Science.gov (United States)

    Bailey, Phillippa; Sarfraz, Farook; Ravanan, Rommel

    2011-11-15

    A 23-year-old female who presented with advanced renal failure was subsequently diagnosed with renal vein thrombosis and antiglomerular basement membrane (GBM) antibody disease. A previous case of renal vein thrombosis has been reported in association with anti-GBM disease, but to our knowledge, this is the first reported case in which the presentation of anti-GBM disease and renal vein thrombosis was concurrent. Further study is essential to understand if the association of anti-GBM disease and renal vein thrombosis as seen in our case was pure coincidence or is in fact occurs more frequently. It may be that the dual diagnosis is not made as establishing one sufficient diagnosis for renal failure may halt further investigations for additional diagnoses.

  8. Membrane Omega-3 Fatty Acid Deficiency as a Preventable Risk Factor for Comorbid Coronary Heart Disease in Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Robert K. McNamara

    2009-01-01

    Full Text Available Major depression disorder (MDD significantly increases the risk for coronary heart disease (CHD which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS and increases risk for mortality. Here evidence implicating omega-3 (n-3 fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

  9. Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA

    Directory of Open Access Journals (Sweden)

    Oleastro Monica

    2009-06-01

    Full Text Available Abstract Background homB encodes a Helicobacter pylori outer membrane protein. This gene was previously associated with peptic ulcer disease (PUD and was shown to induce activation of interleukin-8 secretion in vitro, as well as contributing to bacterial adherence. Its 90%-similar gene, homA, was previously correlated with gastritis. The present study aimed to evaluate the gastric disease association with homB and homA, as well as with the H. pylori virulence factors cagA, babA and vacA, in 415 H. pylori strains isolated from patients from East Asian and Western countries. The correlation among these genotypes was also evaluated. Results Both homB and homA genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains. In Western strains (n = 234, 124 PUD and 110 non-ulcer dyspepsia (NUD, homB, cagA and vacA s1 were all significantly associated with PUD (p = 0.025, p = 0.014, p = 0.039, respectively, and homA was closely correlated with NUD (p = 0.072. In East Asian strains (n = 138, 73 PUD and 65 NUD, homB was found more frequently than homA, and none of these genes was associated with the clinical outcome. Overall, homB was associated with the presence of cagA (p = 0.043 and vacA s1 (p homA was found more frequently in cagA-negative (p = 0.062 and vacA s2 (p Polymorphisms in homB and homA copy number were observed, with a clear geographical specificity, suggesting an involvement of these genes in host adaptation. A correlation between the homB two-copy genotype and PUD was also observed, emphasizing the role of homB in the virulence of the strain. Conclusion The global results suggest that homB and homA contribute to the determination of clinical outcome.

  10. Membrane dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    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...

  11. 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

    2015-01-01

    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...

  12. Basement topography of the Kathmandu Basin using microtremor observation

    Science.gov (United States)

    Paudyal, Youb Raj; Yatabe, Ryuichi; Bhandary, Netra Prakash; Dahal, Ranjan Kumar

    2013-01-01

    Kathmandu Valley, an intermontane basin of the Himalaya, has experienced many destructive earthquakes in the past. The observations of the damage pattern during the 1934 Earthquake (Mw = 8.1), in particular, suggest that the spectral ground amplification due to fluvio-lacustrine sediments plays a major role in intensifying the ground motion in the basin. It is, therefore, imperative to conduct a detailed study about the floor variation of sediments in the basin. In this paper, a preliminary attempt was made to estimate the thickness of soft sediment in the Kathmandu Basin using microtremor observations. The measurements of microtremors were carried out at 172 sites spaced at a grid interval of 1 km. The results showed that the predominant frequency varies from 0.488 Hz to 8.9 Hz. A non-linear regression relationship between resonance frequency and sediment depth was proposed for the Kathmandu Basin. The thickness of lacustrine sediments at various points in the basin was estimated using the proposed equation, and then the estimated thickness was used to plot a digital elevation model of the basement topography and cross profiles of the sediment distribution in the basin. The results were validated by correlating the estimated sediment thickness with geology and geomorphology of the study area.

  13. Magnetically inferred basement structure in central Saudi Arabia

    Science.gov (United States)

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

    1995-05-01

    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.

  14. Cell proliferation in human epiretinal membranes: characterization of cell types and correlation with disease condition and duration

    NARCIS (Netherlands)

    Lesnik Oberstein, S.Y.; Byun, J.; Herrera, D.; Chapin, E.A.; Fisher, S.K.; Lewis, G.P.

    2011-01-01

    To quantify the extent of cellular proliferation and immunohistochemically characterize the proliferating cell types in epiretinal membranes (ERMS) from four different conditions: proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, post-retinal detachment, and idiopathic ERM.

  15. Diagnosis of Helicobacter pylori infection and diseases associated with Helicobacter pylori by Helicobacter pylori outer membrane proteins

    Institute of Scientific and Technical Information of China (English)

    Zheng Jiang; Ai-Long Huang; Xiao-Hong Tao; Pi-Long Wang

    2004-01-01

    AIM: To examine the serological response of patients with upper gastrointestinal diseases and Helicobocter pylori(Hpylori)infection to two H pylori outer membrane proteins (OMPs)(Mr18 000 and Mr26 000) acquired by gene recombinanttechnique, and to determine the diagnostic significance of serological tests derived from these OMPs.METHODS: Recombinant vectors encoding the two H pylori OMPs were used to transform and express in BL21 (DE3)E. coli. After purification with Ni2+-NTA agarose resin, colloid gold kits were prepared with purified recombinant proteins to detect H pylori infection and H pylori-associated diseases by the immunity-marker technology. We selected 150 patients with H pyloriinfection and digestive symptoms without previous treatment, induding chronic gastritis (n = 60), duodenal ulcer (n = 30), gastric ulcer (n = 30), and gastric cancer (n = 30).As controls, 33 H pylori-negative healthy volunteers were also recruited. Serum samples were collected from all subjects, and the antibodies to specific proteins of H pylori were tested with the colloid gold test kits. The sensitivity,specificity and accuracy of the colloid gold tests were evaluated, by using the combination of standard diagnostic methods (13C urea breath test and bacteria culture) and classic enzyme-linked immunosorbent assay (ELISA) as reference.RESULTS: After purification with Ni2+-NTA agarose resin,the purity of recombinant fusion proteins was about 95%.The recombinant fusion proteins were recognized by the specific monoclonal antibodies against the two H pylori OMPs,as demonstrated by the ELISA. Of the 150 serum samples from patients infected with H pylori 141 (94.0%) responded positively to the recombinant protein with Mr26 000, while the seropositive rates were 95.0%, 96.7%, 96.7% and 90.0%for patients with H pylori-associated chronic gastritis,duodenal ulcer, gastric ulcer, and gastric cancer respectively.The sensitivity, specificity, and accuracy of the colloid gold kit with Mr26 000

  16. 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

    2003-01-01

    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.

  17. Altered membrane NTPase activity in Lesch-Nyhan disease fibroblasts: comparison with HPRT knockout mice and HPRT-deficient cell lines.

    Science.gov (United States)

    Pinto, Cibele S; Jinnah, Hyder A; Shirley, Thomas L; Nyhan, William L; Seifert, Roland

    2005-06-01

    Lesch-Nyhan disease (LND) is a rare disorder caused by a defect of an enzyme in the purine salvage pathway, hypoxanthine phosphoribosyl transferase (HPRT). It is still unknown how the metabolic defect translates into the complex neuropsychiatric phenotype characterized by self-injurious behavior, dystonia and mental retardation. There are abnormalities in purine and pyrimidine nucleotide content in HPRT-deficient cells. We hypothesized that altered nucleotide concentrations in HPRT deficiency change G-protein-mediated signal transduction. Therefore, our original study aim was to examine the high-affinity GTPase activity of G-proteins in membranes from primary human skin and immortalized mouse skin fibroblasts, rat B103 neuroblastoma cells and mouse Neuro-2a neuroblastoma cells. Unexpectedly, in membranes from human fibroblasts, B103- and Neuro-2a cells, V(max) of low-affinity nucleoside 5'-triphosphatase (NTPase) activities was decreased up to 7-fold in HPRT deficiency. In contrast, in membranes from mouse fibroblasts, HPRT deficiency increased NTPase activity up to 4-fold. The various systems analyzed differed from each other in terms of K(m) values for NTPs, absolute V(max) values and K(i) values for nucleoside 5'-[beta,gamma-imido]triphosphates. Our data show that altered membrane NTPase activity is a biochemical hallmark of HPRT deficiency, but species and cell-type differences have to be considered. Thus, future studies on biochemical changes in LND should be conducted in parallel in several HPRT-deficient systems.

  18. Application of Human Amniotic Membrane in Canine Penile Tunica Albuginea Defect: First Step toward an Innovating New Method for Treatment of Peyronie?s Disease

    Directory of Open Access Journals (Sweden)

    M. Salehipour

    2014-06-01

    Full Text Available Purposes To evaluate the efficacy of human amniotic membrane (AM grafting in the canine penile tunica albuginea defect; we developed an animal model as the first step toward an innovating new method for the treatment of Peyronie’s disease, penile cancers, and congenital deformities of the penis. Material and Methods From August to September 2011, ten healthy male dogs were selected. A rhomboid incision about 3x2cm over the tunica albuginea and its overlying squamous epithelium was made and then excised. The amniotic membrane was folded twice on itself and grafted on the defect. After 8 weeks, artificial erection was made for 5 dogs and for the other 5 dogs after 12 weeks. After artificial erection, partial penectomy was done and histopathological evaluation was performed on the grafts. Results Artificial erection performed successfully in all of the dogs. No infection or any other complication was seen. Histopathological examination showed complete re-epithelialization with squamous epithelium and collagen fiber deposition. Also, no dysplasia was seen. Conclusions The amniotic membrane can be used as a suitable substitution for tunica albuginea. It is safe, inexpensive, biodegradable, and available and may be used for the treatment of Peyronie’s disease, penile cancers, congenital penile deformities, and penile reconstructive surgery.

  19. [Indices of total lipids in erythrocyte membranes and blood plasma in patients with gingivitis in the presence of concomitant diseases and after antioxidant therapy].

    Science.gov (United States)

    Zhirova, V G

    2001-01-01

    Enrolled in this study were those children of both sexes (n=82) from ecologically unfavourable zones who had been admitted to the Yevpatoriya sanatorium "Druzhba" (Frendship) for the rehabilitative period, their age ranging between 11 to 14 years. Our objective in this examination was to study total lipids in red cell membranes and blood plasma in using the antioxidant erbisol to treat inflammatory disease of the oral mucosa in the presence of concomitant illnesses. The performed analysis of the data obtained permitted reaching the conclusion that treatment of parodontal disorders having developed in the presence of concomitant troubles using in a complex therapy erbisol class antioxidants results in a decrease of activation of lipid peroxidation processes in red cell membranes and blood plasma, which fact has found confirmation in an apparent therapeutic effect.

  20. Minimal change disease: a CD80 podocytopathy?

    Science.gov (United States)

    Ishimoto, Takuji; Shimada, Michiko; Araya, Carlos E; Huskey, Janna; Garin, Eduardo H; Johnson, Richard J

    2011-07-01

    Minimal change disease is the most common nephrotic syndrome in children. Although the etiology of minimal change disease remains to be elucidated, it has been postulated that it is the result of a circulating T-cell factor that causes podocyte cytoskeleton disorganization leading to increased glomerular capillary permeability and/or changes in glomerular basement membrane heparan sulfate glycosaminoglycans resulting in proteinuria. Minimal change disease has been associated with allergies and Hodgkin disease. Consistent with these associations, a role for interleukin-13 with minimal change disease has been proposed. Furthermore, studies evaluating podocytes also have evolved. Recently, increased expression of CD80 (also termed B7-1) on podocytes was identified as a mechanism for proteinuria. CD80 is inhibited by binding to CTLA-4, which is expressed on regulatory T cells. Recently, we showed that urinary CD80 is increased in minimal change disease patients and limited studies have suggested that it is not commonly present in the urine of patients with other glomerular diseases. Interleukin-13 or microbial products via Toll-like receptors could be factors that induce CD80 expression on podocytes. CTLA-4 appears to regulate CD80 expression in podocytes, and to be altered in minimal change disease patients. These findings lead us to suggest that proteinuria in minimal change disease is caused by persistent CD80 expression in podocytes, possibly initiated by stimulation of these cells by antigens or cytokines.

  1. 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

    2003-01-01

    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.

  2. Retinal Damage Induced by Internal Limiting Membrane Removal

    Directory of Open Access Journals (Sweden)

    Rachel Gelman

    2015-01-01

    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.

  3. Primary Sjögren's syndrome with minimal change disease--a case report.

    Science.gov (United States)

    Yang, Mei-Li; Kuo, Mei-Chuan; Ou, Tsan-Teng; Chen, Hung-Chun

    2011-05-01

    Glomerular involvement in patients with primary Sjögren's syndrome (pSS) has rarely been reported. Among them, membranoproliferative glomerulonephritis and membranous nephropathy are the more common types. We report a middle-aged female presenting concurrently with nephrotic syndrome and microscopic hematuria, and her pSS was diagnosed by positive anti-Ro (SSA)/anti-La (SSB) autoantibodies, dry mouth, severely diffuse impaired function of both bilateral parotid and submandibular glands, and a positive Schirmer test. Renal pathology revealed minimal change disease and thin basement membrane nephropathy. The patient's nephrotic syndrome resolved after treatment with corticosteroids. To our knowledge, this is the first report of minimal change disease in a patient with pSS.

  4. [Anti-phospholipase A2 receptor (anti-PLA2R) antibodies and idiopathic membranous nephropathy: which role in diagnosis and prognosis of this disease?].

    Science.gov (United States)

    Netti, Giuseppe Stefano; Ranieri, Elena

    2014-01-01

    The discovery of the M-type phospholipase A2 receptor (PLA2R) as a major antigen in idiopathic membranous nephropathy (iMN) was a breakthrough in understanding the pathogenesis of this disease, establishing iMN as an autoimmune disease. Subsequent studies confirmed that detection of circulating antibodies against PLA2R was positive in approximately 70% of incident iMN patients. We discuss several studies that have suggested the potential role of measuring PLA2R antibodies for clinical practice. Recently, it has been shown that the presence of PLA2R antibodies supported a diagnosis of iMN, changes in antibody levels were related to clinical disease activity, disappearance of antibodies preceded and predicted subsequent decrease of proteinuria and high titers of antibodies were associated with a low likelihood spontaneous remission.

  5. 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)

    1998-02-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Miqdam Tariq Chaichan

    2011-01-01

    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.

  7. Efficacy of a second course of immunosuppressive therapy in patients with membranous nephropathy and persistent or relapsing disease activity.

    NARCIS (Netherlands)

    Buf-Vereijken, P.W.G. du; Wetzels, J.F.M.

    2004-01-01

    BACKGROUND: A single course of immunosuppressive treatment improves renal survival in patients with idiopathic membranous nephropathy (iMN) and renal insufficiency. However, not all patients respond and relapses occur within 5 years in 30% of patients. It is unknown if a second course of

  8. Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy.

    Science.gov (United States)

    Brenchley, P E; Coupes, B; Short, C D; O'Donoghue, D J; Ballardie, F W; Mallick, N P

    1992-04-01

    We have measured complement activation markers, C3dg and C5b-9 in plasma and urine from patients with idiopathic membranous nephropathy and IgA nephropathy. There was no significant difference in levels of plasma C5b-9 between the patient groups. However, high plasma concentrations of C3dg were associated significantly with IgA nephropathy with 45% of patients having levels over 25 U/ml (P less than 0.001). High concentrations of urinary C3dg and C5b-9 were associated significantly with membranous nephropathy (43% and 43% of the patient group, respectively) compared to patients with IgA nephropathy (10% and 0%, respectively, P less than 0.001). In a retrospective analysis of 31 patients with membranous nephropathy, 66% of patients with high initial urinary C5b-9 showed an unstable clinical course compared to 18% of patients with initially absent or low C5b-9 (P less than 0.001). We suggest that high urinary C5b-9 identifies those patients with a membranous lesion which retains an active immunological component contributing to the pathology of progressive glomerular damage.

  9. 鼻塞式CPAP治疗新生儿肺透明膜病疗效观察%Efficacy of Hyaline Membrane Disease Nasal CPAP Treatment

    Institute of Scientific and Technical Information of China (English)

    艾力甫

    2015-01-01

    目的:观察鼻塞式CPAP(NCPAP)治疗新生儿肺透明膜病的疗效。方法对20例早期新生儿肺透明膜病进行X线检查,根据血气分析结果调整呼吸机参数。结果20例患儿放弃治疗1例,转上级医院治疗1例,余18例顺利撤除鼻塞式CPAP。结论鼻塞式CPAP治疗早期新生儿肺透出明膜病能明显的提高治疗效果,对早产儿非常适用。%Objective To observe the nasal CPAP (NCPAP)therapy hyaline membrane disease.Methods 20 cases of early neonatal hyaline membrane disease,X-ray inspection,adjustment of ventilator parameters based on the results of blood gas analysis.Results 20 patients gave up treatment one case,turn higher hospital one case,more than 18 cases of successful removal of nasal CPAP.Conclusion Nasal CPAP treatment early neonatal lung disease,revealed a clear film can significantly improve the therapeutic ef ect,very suitable for preterm children.

  10. 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

    2001-01-01

    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

  11. ATP-ases of synaptic plasma membranes in striatum: enzymatic systems for synapses functionality by in vivo administration of L-acetylcarnitine in relation to Parkinson's Disease.

    Science.gov (United States)

    Villa, R F; Ferrari, F; Gorini, A

    2013-09-17

    The maximum rate (Vmax) of some enzymatic activities related to energy consumption was evaluated in synaptic plasma membranes from rat brain striatum, the synaptic energy state being a crucial factor in neurodegenerative diseases etiopathogenesis. Two types of synaptic plasma membranes were isolated from rats subjected to in vivo treatment with L-acetylcarnitine at two different doses (30 and 60 mg × kg(-1) i.p., 28 days, 5 days/week). The following enzyme activities were evaluated: acetylcholinesterase (AChE); Na(+), K(+), Mg(2+)-ATP-ase; ouabain insensitive Mg(2+)-ATP-ase; Na(+), K(+)-ATP-ase; direct Mg(2+)-ATP-ase; Ca(2+), Mg(2+)-ATP-ase; and low- and high-affinity Ca(2+)-ATP-ase. In control (vehicle-treated) animals, enzymatic activities are differently expressed in synaptic plasma membranes type I (SPM1) with respect to synaptic plasma membranes type II (SPM2), the evaluated enzymatic activities being higher in SPM2. Subchronic treatment with L-acetylcarnitine decreased AChE on SPM1 and SPM2 at the dose of 30 mg × kg(-1). Pharmacological treatment decreased ouabain insensitive Mg(2+)-ATP-ase activity and high affinity Ca(2+)-ATP-ase activity at the doses of 30 and 60 mg × kg(-1) respectively on SPM1, while it decreased Na(+), K(+)-ATP-ase, direct Mg(2+)-ATP-ase and Ca(2+), Mg(2+)-ATP-ase activities at the dose of 30 mg × kg(-1) on SPM2. These results suggest that the sensitivity to drug treatment is different between these two populations of synaptic plasma membranes from the striatum, confirming the micro-heterogeneity of these subfractions, possessing different metabolic machinery with respect to energy consumption and utilization and the regional selective effect of L-acetylcarnitine on cerebral tissue, depending on the considered area. The drug potential effect at the synaptic level in Parkinson's Disease neuroprotection is also discussed with respect to acetylcholine and energy metabolism.

  12. 新生儿肺透明膜病及湿肺病的分类决策诊断%Classification decision tree in differentiating wet lung disease from hyaline membrane disease of newborns

    Institute of Scientific and Technical Information of China (English)

    施莉丽; 吴伟军; 张骥; 罗剑锋

    2012-01-01

    Objective To establish classification and regression tree for differentiating wet lung disease from hyaline membrane disease, and to discuss the diagnostic value of the relative clinical presentations and x-ray findings. Methods Forty-three cases of hyaline membrane disease and forty-eight cases of wet lung disease of newborns were analyzed retrospectively. Six clinical presentations and seven X-ray findings were collected as predictors. A classification tree was established to distinguish the two diseases. In the observing test, one senior radiologist was independently presented with clinical information and X-ray findings without knowing The correct diagnosis. Meanwhile, statistic analysis was used to compare the diagnostic agreement of CART model and the senior radiologist. Results The model of CART, in which there were nine diagnostic paths, could reliably diagnose wet lung disease from hyaline membrane disease. CART showed that air bronchogram, gestational weeks, ground glass appearance and horizontal fissure were of important diagnostic value. Kappa analysis showed the diagnostic agreement of CART and the senior radiologist was 0. 553 (wet lung disease, medium agreement) and 0. 628 (hyaline membrane disease, high agreement). Conclusion CART can provide a high accuracy in differentiating wet lung disease from hyaline membrane disease. The sign of air bronchogram, gestational weeks, ground glass appearance, and horizontal fissure are important diagnostic predictors.%目的 应用分类决策树(classification and regression tree,CART)算法构建胸片鉴别新生儿透明膜病及湿肺病的诊断模型,探讨多种临床及影像因素对肺透明膜病及湿肺病的诊断价值.方法 病例为2008年1月~2010年12月间经过临床及影像证实的新生儿肺透明膜病43例、湿肺病48例.分别提取和上述两种疾病有关的6个临床指标和7个影像学指标作为CART预测新生儿肺透明膜病及湿肺病的变量.用CART建立两

  13. Cholesterol-Dependent Energy Transfer between Fluorescent Proteins—Insights into Protein Proximity of APP and BACE1 in Different Membranes in Niemann-Pick Type C Disease Cells

    Directory of Open Access Journals (Sweden)

    Bjoern von Einem

    2012-11-01

    Full Text Available Förster resonance energy transfer (FRET -based techniques have recently been applied to study the interactions between β-site APP-cleaving enzyme-GFP (BACE1-GFP and amyloid precursor protein-mRFP (APP-mRFP in U373 glioblastoma cells. In this context, the role of APP-BACE1 proximity in Alzheimer’s disease (AD pathogenesis has been discussed. FRET was found to depend on intracellular cholesterol levels and associated alterations in membrane stiffness. Here, NPC1 null cells (CHO-NPC1−/−, exhibiting increased cholesterol levels and disturbed cholesterol transport similar to that observed in Niemann-Pick type C disease (NPC, were used to analyze the influence of altered cholesterol levels on APP-BACE1 proximity. Fluorescence lifetime measurements of whole CHO-wild type (WT and CHO-NPC1−/− cells (EPI-illumination microscopy, as well as their plasma membranes (total internal reflection fluorescence microscopy, TIRFM, were performed. Additionally, generalized polarization (GP measurements of CHO-WT and CHO-NPC1−/− cells incubated with the fluorescence marker laurdan were performed to determine membrane stiffness of plasma- and intracellular-membranes. CHO-NPC1−/− cells showed higher membrane stiffness at intracellular- but not plasma-membranes, equivalent to cholesterol accumulation in late endosomes/lysosomes. Along with higher membrane stiffness, the FRET efficiency between BACE1-GFP and APP-mRFP was reduced at intracellular membranes, but not within the plasma membrane of CHO-NPC1−/−. Our data show that FRET combined with TIRF is a powerful technique to determine protein proximity and membrane fluidity in cellular models of neurodegenerative diseases.

  14. Membrane reactor. Membrane reactor

    Energy Technology Data Exchange (ETDEWEB)

    Shindo, Y.; Wakabayashi, K. (National Chemical Laboratory for Industry, Tsukuba (Japan))

    1990-08-05

    Many reaction examples were introduced of membrane reactor, to be on the point of forming a new region in the field of chemical technology. It is a reactor to exhibit excellent function, by its being installed with membrane therein, and is generally classified into catalyst function type and reaction promotion type. What firstly belongs to the former is stabilized zirconia, where oxygen, supplied to the cathodic side of membrane with voltage, impressed thereon, becomes O {sup 2 {minus}} to be diffused through the membrane and supplied, as variously activated oxygenous species, on the anodic side. Examples with many advantages can be given such as methane coupling, propylene oxidation, methanating reaction of carbon dioxide, etc. Apart, palladium film and naphion film also belong to the former. While examples of the latter comprise, among others, decomposition of hydrogen sulfide by porous glass film and dehydrogenation of cyclohexane or palladium alloy film, which are expected to be developed and materialized in the industry. 33 refs., 8 figs.

  15. 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

    2004-01-01

    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.

  16. Late-Paleozoic emplacement and Meso-Cenozoic reactivation of the southern Kazakhstan granitoid basement

    Science.gov (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

    2015-11-01

    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.

  17. Disease: H01221 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available the epithelium are the hallmarks of EBMD. Most patients are asymptomatic before ...roche L, Abitbol M, Schorderet DF A subset of patients with epithelial basement membrane corneal dystrophy have mutations in TGFBI/BIGH3. Hum Mutat 27:553-7 (2006) ...

  18. Disease: H00578 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available of cataracts and blue leukocyte inclusion bodies (Doehle-like bodies). Both disorders...iption) Kashtan CE, Segal Y Genetic disorders of glomerular basement membranes. Nephron Clin Pract 118:c9-c1...H, Park YS, Ha IS, Ahn HS, Choi Y, Cheong HI Renal manifestations of patients with MYH9-related disorders. Pediatr Nephrol 26:549-55 (2011) ...

  19. Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival

    Directory of Open Access Journals (Sweden)

    Yusuke Toyoda

    2014-07-01

    Full Text Available Parkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes linked with the onset of Parkinson's disease, DJ-1/PARK7, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson's related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson's disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson's disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson's disease.

  20. Biocompatible dialysis membranes and oxidative stress in patients wih end-stage renal disease on maintenance haemodialysis.

    Science.gov (United States)

    Abdel-Naeem, Nareman M; Kandell, Nagwa F; El-Shamaa, Azza A; Harba, Tarek M; Abdel-Hady, Afaf A

    2005-12-01

    Oxidative stress has been shown in (ESRD) patients specially those receiving regular haemodialysis (HD) in relation with an increased production of toxic free radicals due to membrane-induced complement leukocyte activation. An imbalance between oxidants and antioxidans has been suggested in uremic patients on HD. The respective influence of uremia and dialysis procedure has not been evaluated. Studies that have probed into the mechanism of oxygen radical production have implicated the bio-incompatibility of dialysis membranes. The effect of different dialysis membranes on lipid, lipoproteins, lipid peroxidation and total antioxidant capacity in ESRD patients on regular HD was studied. One hundred subjects were selected; 20 healthy controls, 20 chronic renal failure (CRF) patients on conservative drug management and 60 CRF patients on maintenance HD (20 dialyzed by polysulfone, 20 by hemophan and 20 by cuprophane membranes). All patients were matched for age, sex, gender and etiology of ESRD and HD patients for duration of dialysis. In addition to routine tests (Hb% and creatinine clearance in healthy control group and CRF patients on conservative management), total cholesterol, triglycerides, high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C), apolipoprotein A (Apo A), apolipoprotein B (Apo B), serum malondialdehyde (MDA) and plasma total antioxidant status (TAS) were estimated. MDA was significantly higher and TAS was lower in uremic patients treated conservatively or by HD than in controls. MDA was significantly higher in HD than CRF patients on conservative management with least significant difference in HD patients treated by polysulfone followed by hemophan and then cuprophane membrane, while only cuprophane group showed lower levels of TAS compared to CRF patients on conservative management. HDL-C and Apo A was higher in polysulfone and hemophan than cuprophane group while triglyderide was lower. Polysulfone group showed lower levels of LDL

  1. Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Hansen, M; Stoltenberg, M;

    1999-01-01

    OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying a......OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease......-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P

  2. Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Hansen, M; Stoltenberg, M

    1999-01-01

    OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying a......OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease......-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P

  3. Biobased Membrane

    NARCIS (Netherlands)

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

    2015-01-01

    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

  4. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    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....

  5. Herlyn-Werner-Wunderlich Syndrome with Unilateral Hemivaginal Obstruction, Ipsilateral Renal Agenesis, and Contralateral Renal Thin GBM Disease: A Case Report with Radiological Follow Up

    Energy Technology Data Exchange (ETDEWEB)

    Park, Noh Hyuck; Park, Hee Jin; Park, Chan Sup [Myongji Hospital, Kwandong University, Koyang (Korea, Republic of); Park, Sung Il [Bucheon Hospital, Soonchunhyang University, Bucheon (Korea, Republic of)

    2010-08-15

    Herlyn-Werner-Wunderlich syndrome is a rare Mullerian ductal anomaly that is characterized by the presence of a hemivaginal septum, a didelphic uterus and ipsilateral renal agenesis. It is generally difficult to diagnose the uterine malformation before menarche owing to its small size. Therefore, a follow-up study is very important for confirming the uterine malformation in girls with renal agenesis. We report a patient with renal agenesis and microscopic hematuria, who showed symptoms before menarche. A follow-up study eventually revealed uterine didelphys with a hemivaginal obstruction. A biopsy proved that the microscopic hematuria was caused by thin glomerular basement membrane disease of the contralateral kidney

  6. Fracture and vein characterization of a crystalline basement reservoir, central Yemen

    Science.gov (United States)

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

    2012-04-01

    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

  7. Fold deformations of the paleozoic basement roof in the Chunkurchak Trough, Kyrgyz Ala-Too Range

    Science.gov (United States)

    Przhiyalgovskii, E. S.; Lavrushina, E. V.

    2017-07-01

    A structural-geological study has been performed on the northern slope of the Kyrgyz Ala-Too Range. Deformations of the peneplaned Paleozoic basement surface, structures of granite disintegration, and morphostructural manifestation of Late Cenozoic tectonic movements have been investigated. Based on the location of pre-Paleocene peneplain remnants with the retained weathering mantle partly overlapped by Paleocene-Miocene sedimentary complexes, we have reconstructed the morphology of the folded surface of the Chunkurchak Trough separated from the Chu Basin at the early Miocene. The dome-fold forms, the morphology and arrangement of which are controlled by disintegration of the basement, have been described for the basement surface. It has been established that granites are broken by systems of steeply dipping, fanshaped, and gently dipping faults and fractures. Variously oriented insignificant offsets along slickensides, as well as displacements deduced from the geometry of fracture intersections, are a result of volumetric cataclastic flow of rocks. The tectonic mobility of disintegrated granites, which are abundant in the Paleozoic-Precambrian basement, explains the complexity and scale of tectonic processes initiated by Cenozoic activation. In paleotectonic reconstructions, which take into consideration tectonic flow and the redistribution of basement masses, the estimates of Cenozoic relative rapprochement of the Chu Basin and the Kyrgyz Ala-Too Range decrease substantially to 4-6 km.

  8. Simulation modeling of vegetation effects on [sup 222]Rn transport into basements

    Energy Technology Data Exchange (ETDEWEB)

    Morris, R.C.

    1992-01-01

    The author developed a model of [sup 222]Rn transport through soils and into experimental basements. The model was based on current theories and data from the Radon Project experimental basements at Colorado State University were used to calibrate it to that site. Uncertainty analysis of the model showed that model predictions of indoor [sup 222]Rn concentrations come from a distribution having a CV of no greater than 0.25. Sensitivity analysis of the model indicated that the dry bulk density, the [sup 226]Ra concentration of the soil and the effective permeability of the basement wall are, perhaps, the most important parameters in the model for determining a set of output. The effective diffusion coefficient of the basement wall is also important. The model was perturbed in manners consistent with three expected mechanisms, and their combination, by which vegetation might influence indoor [sup 222]Rn concentration. The presence of vegetation, acting by any mechanism, reduces indoor [sup 222]Rn concentration. Vegetation also influences the pattern in time of indoor [sup 222]Rn. In general, indoor [sup 222]Rn concentrations tend to follow surface soil moisture, with variability added to the trend by the wind speed. This pattern was modified, however, by vegetation action. Based on these results, I developed a set of predictions which can be tested by experiment at the Radon Project experimental basements to determine which of the hypothesized mechanisms of vegetation action is supported.

  9. 新生儿肺透明膜病的多层螺旋CT诊断%The MSCT Diagnosis of Neonatal Hyaline Membrane Disease

    Institute of Scientific and Technical Information of China (English)

    韦学; 谭俊扬; 胡琪琳; 廖保荣

    2011-01-01

    Objective To explore the Spiral CT signs of neonatal hyaline membrane disease .Analysis its Pathogenesis and clinical manifestation through literature review in order to improve the understanding of the disease. Methods Analyze our hospital 18 cases of neonatal hyaline membrane disease from May 2008 to March 2011 especially focus on the multislice CT imaging features. Results Grinding glass phenomenon of double lung among all cases, including air-filled bronchi imaging levy in 12 cases, white lung change 1 case, pneumothorax 4 cases, pneumomediastinum 2 cases, among them, including Neck soft tissue emphysema 2 cases, pulmonary hemorrhage 1 case. Conclusion The MDCT performance of neonatal hyaline membrane disease has certain characteristic, and can supply the evidence for imaging diagnosis this lesion.%目的 探讨新生儿肺透明膜病的螺旋CT征象特点,分析其发病机制及临床表现,通过复习文献,提高对该病的认识.方法 分析我院自2008年5月至2011年3月具有完整资料的肺透明膜病18例,着重分析多层螺旋CT对其肺部的病灶显示能力及影像学特征.结果 本组病例中全部出现双肺透亮度降低的磨玻璃样影及小颗粒样影,其中合并出现支气管充气造影征12例,白肺改变1例,气胸4例,纵隔气肿2例,其中1例合并颈部软组织内气肿.合并肺出血1例.结论 新生儿肺透明膜病多层螺旋CT表现有一定的特征性,可为临床提供重要的影像学依据.

  10. New Treatment for Band Keratopathy: Superficial Lamellar Keratectomy, EDTA Chelation and Amniotic Membrane Transplantation

    Science.gov (United States)

    Kwon, Young Sam; Song, Young Soo

    2004-01-01

    We report two cases of band keratopathy who were treated with thick amniotic membrane that contained a basement membrane structure as a graft, after ethylenediaminetetraacetic acid chelation with trephination and blunt superficial lamellar keratectomy in the anterior stroma. In each case, basement membrane was destroyed and calcium plaque invaded into anterior stroma beneath Bowman's membrane. The calcified lesions were removed surgically, resulting in a smooth ocular surface, and the fine structures of band keratopathy were confirmed by pathologic findings. After that, amniotic membrane transplantation was performed to replace the excised epithelium and stroma. Wound healing was completed within 10 days. Stable ocular surface was restored without pain or inflammation. During the mean follow-up period of 13.5 months, no recurrence of band keratopathy was observed. This combined treatment is a safe and effective method for the removal of deep-situated calcium plaque and allowing the recovery of a stable ocular surface. PMID:15308858

  11. Inversion of gravity data in the Big Bear Lake Area to recover depth to basement using Cauchy-type integrals

    DEFF Research Database (Denmark)

    Cai, Hongzhu; Zhdanov, Michael

    2014-01-01

    One of the important applications of the gravity method is evaluation of the depth to the basement, which is characterized by a significant density contrast with the sedimental layeres. We have introduced recently a new method of modeling and inversion of potential field data generated by a density...... response caused by sediment-basement interface with variable density in depth. We have also developed the inversion of gravity data to recover the depth to basement given the density profile with depth....

  12. Influence of basements, garages, and common hallways on indoor residential volatile organic compound concentrations

    Science.gov (United States)

    Dodson, Robin E.; Levy, Jonathan I.; Spengler, John D.; Shine, James P.; Bennett, Deborah H.

    Concentrations of many volatile organic compounds (VOCs) are often higher inside residences than outdoors as a result of sources or activities within the residences. These sources can be located directly in the living space of the home or in areas associated with the home such as an attached garage, basement, or common apartment hallway. To characterize the contributions from these areas to indoor residential concentrations, VOC concentrations were measured inside, outside, and, if present, in the attached garage, basement, or common hallway of an apartment of 55 residences in the Boston area, most over two seasons, as part of the Boston Exposure Assessment in Microenvironments (BEAM) Study. Of the 55 residences in the study, 11 had attached garages and basements, 24 had only basements, 10 other residences had common apartment hallways, and the remaining 10 were treated as single compartment residences. Concentrations in the garage were up to 5-10 times higher at the median than indoor concentrations for mobile source pollutants including benzene, toluene, ethylbenzene, and xylenes. Basement/indoor concentration ratios were significantly >1 for methylene chloride, ethylbenzene, m, p-xylene, and o-xylene, and summer ratios tended to be higher than winter ratios. Approximately, 20-40% of the indoor concentration for compounds associated with gasoline sources, such as methyl t-butyl ether (MTBE), benzene, toluene, ethylbenzene, and xylenes, can be attributed to an attached garage at the residence, with garages laterally attached to the first floor of the home having a larger impact. At the median, basements contributed to approximately 10-20% of the estimated indoor concentrations. For apartments, approximately 5-10% of the estimated indoor concentrations confer with air from the hallway. Contributions of these secondary zones to concentrations in the living area of a home were calculated using concentration and airflow estimates. Our findings illustrate the potential

  13. The surface of crystalline basement, Great Valley and Sierra Nevada, California: A digital map database

    Science.gov (United States)

    Wentworth, Carl M.; Fisher, G. Reid; Levine, Paia; Jachens, Robert C.

    1995-01-01

    Crystalline basement in central California extends westward from the exposed Sierra Nevada beneath the sedimentary fill of the Great Valley and under the eastern edge of the Coast Ranges at mid-crustal depth. The surface of this basement is defined from three types of control: in the Sierra Nevada from the topography itself, beneath the eastern two thirds of the Great Valley in considerable detail from numerous wells drilled for oil and gas, and beneath the western San Joaquin Valley in less detail from seismic reflection and refraction profiles. Together, these data demonstrate that the surface of crystalline rock is continuous from the exposed rock in the mountains to the top of high-velocity rock buried deep beneath the eastern front of the southern Coast Ranges. This report presents a compilation of data through 1985 that define the surface of this crystalline basement, a contour map of the surface, and the lithology of the basement rock sampled by many of the wells. The compilation was begun as part of the investigation of the 1983 Coalinga earthquake, and was subsequently converted to digital form and extended to the whole of the Great Valley and Sierra Nevada. The main purpose was to explore and document the shape and continuity of the basement surface and to determine the relation of the surface to the tectonic wedge hypothesis (Wentworth and others, 1984; Wentworth and Zoback, 1989). Available basement samples from wells - principally the thin-section collection of May and Hewitt (1948) preserved by the California Academy of Sciences - were also reexamined by cooperating petrologists in an effort to distinguish wells that bottomed in ophiolitic rocks.

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

    Science.gov (United States)

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

    2013-12-01

    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.

  15. Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy

    NARCIS (Netherlands)

    Baeten, D; Kruithof, E; De Rycke, L; Boots, AM; Mielants, H; Veys, EM; De Keyser, F

    2005-01-01

    Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes

  16. Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy

    NARCIS (Netherlands)

    Baeten, D; Kruithof, E; De Rycke, L; Boots, AM; Mielants, H; Veys, EM; De Keyser, F

    2005-01-01

    Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes a

  17. Analogue experiments of salt flow and pillow growth due to basement faulting and differential loading

    Science.gov (United States)

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

    2015-01-01

    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

  18. Analogue experiments of salt flow and pillow growth due basement faulting and differential loading

    Science.gov (United States)

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

    2014-07-01

    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

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    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.

  20. Heterogeneous histologic and clinical evolution in 3 cases of dense deposit disease with long-term follow-up.

    Science.gov (United States)

    Figuères, Marie-Lucile; Frémeaux-Bacchi, Véronique; Rabant, Marion; Galmiche, Louise; Marinozzi, Maria Chiara; Grünfeld, Jean-Pierre; Noël, Laure-Hélène; Servais, Aude

    2014-11-01

    Dense deposit disease is characterized by dense deposits in the glomerular and tubular basement membranes. We report 3 cases with long-term follow-up differing in histologic pattern and clinical evolution. Clinical and histologic data were collected between 1976 and 2012. Age at the first manifestations was 6, 11, and 23 years, respectively. They included proteinuria (patient 1) and nephrotic syndrome (patients 2 and 3); renal function was normal in all cases. Two patients (1 and 3) had low complement component 3 (C3) levels. All patients had C3 nephritic factor. Genetic analysis revealed a rare variant of the factor I gene (patient 1) and a heterozygous mutation in complement factor H-related 5 gene (patient 2). Patient 1 underwent 3 biopsies during her 38 years of follow-up. Thickening of the capillary walls of the glomerular and tubular basement membranes was observed, with mild mesangial proliferation and progressive C3 and complement membrane attack complex mesangial deposits. However, renal function remained normal. Patient 2 also underwent 3 biopsies (22 years of follow-up), revealing a gradual decrease in C3 deposition and mesangial cell proliferation. He presented mild renal insufficiency. Patient 3 underwent 2 biopsies, which displayed unusual bulky membranous deposits, confirmed by electron microscopy, with no mesangial cell proliferation and little C3 and complement membrane attack complex deposits. Kidney function remained normal. These 3 cases of dense deposit disease differed in histologic pattern evolution: accumulation of C3 deposits, decrease in C3 deposits and proliferation, and isolated dense deposits. The histologic factors involved in clinical progression remain to be identified.

  1. Cast nephropathy and light-chain deposition disease in Waldenström macroglobulinemia.

    Science.gov (United States)

    Gnemmi, Viviane; Leleu, Xavier; Provot, François; Moulonguet, Florence; Buob, David

    2012-09-01

    Waldenström macroglobulinemia is a rare low-grade hematologic malignancy due to clonal proliferation of B lymphocytes responsible for immunoglobulin M (IgM) monoclonal gammopathy secreted in serum. This disease is characterized by lymphoplasmacytic tumoral infiltration of bone marrow and various organs, especially the liver and spleen. Kidney involvement in Waldenström macroglobulinemia has been described previously with reports of various forms of glomerular injury: large intracapillary IgM pseudothrombi, cryoglobulinemia-associated membranoproliferative glomerulonephritis, or amyloidosis. Interstitial infiltration by tumoral B lymphocytes is another classic pattern. Conversely, tubular involvement in the form of myeloma-like casts or basement membrane deposition of monoclonal light chain (light-chain deposition disease) is unusual. We report the occurrence of cast nephropathy associated with light-chain deposition disease in 2 patients with Waldenström macroglobulinemia, which resulted in severe and prolonged kidney failure.

  2. Quantification of lipopolysaccharides in outer membrane vesicle vaccines against meningococcal disease. High-performance liquid chromatographic determination of the constituent 3-hydroxy-lauric acid.

    Science.gov (United States)

    Lyngby, Janne; Olsen, Linda H; Eidem, Tove; Lundanes, Elsa; Jantzen, Erik

    2002-03-01

    A high-performance liquid chromatographic (HPLC) assay for quantification of lipopolysaccharides (LPSs, endotoxins) in outer membrane vesicle vaccines against meningococcal disease has been developed. The LPS constituent, 3-hydroxy-lauric acid, served as marker substance for the quantification. LPS from the vaccine was precipitated by ethanol and the fatty acid constituents, including 3-hydroxy-lauric acid, were released by acidic hydrolysis, collected and purified by solid phase extraction on C18 disc-cartridges and converted into phenacyl esters for UV detection at 240 nm. Quantification of the derivatized 3-hydroxy-lauric acid was achieved by HPLC using a Brownlee RP-18 reversed phase column with acetonitrile/water (68:32, v/v) as mobile phase. The method was found to be linear over the range 3-49 microg LPS/ml with a sensitivity of 1.6 (microg/ml)(-1). The repeatability (within-day precision) of the method at three levels (3-49 microg LPS/ml) was 6-14% relative standard deviation and the intermediate (between-day) precision was 7% relative standard deviation (at level 15 microg LPS/ml). The method has been successfully used in the quality control of a meningococcal B outer membrane vesicle vaccine, containing 4-8% LPS relative to protein (w/w), in our laboratory for three years.

  3. Real-time study of E-cadherin and membrane dynamics in living animals: implications for disease modeling and drug development.

    Science.gov (United States)

    Serrels, Alan; Timpson, Paul; Canel, Marta; Schwarz, Juliane P; Carragher, Neil O; Frame, Margaret C; Brunton, Valerie G; Anderson, Kurt I

    2009-04-01

    The ability of tumor cells to invade and metastasize requires deregulation of interactions with adjacent cells and the extracellular matrix. A major challenge of cancer biology is to observe the dynamics of the proteins involved in this process in their functional and physiologic context. Here, for the first time, we have used photobleaching and photoactivation to compare the mobility of cell adhesion and plasma membrane probes in vitro and in tumors grown in mice (in vivo). We find differences between in vitro and in vivo recovery dynamics of two key molecules, the tumor suppressor E-cadherin and the membrane-targeting sequence of H-Ras. Our data show that E-cadherin dynamics are significantly faster in vivo compared with cultured cells, that the ratio of E-cadherin stabilized in cell-cell junctions is significantly higher in vivo, and that E-cadherin mobility correlates with cell migration. Moreover, quantitative imaging has allowed us to assess the effects of therapeutic intervention on E-cadherin dynamics using dasatinib, a clinically approved Src inhibitor, and show clear differences in the efficacy of drug treatment in vivo. Our results show for the first time the utility of photobleaching and photoactivation in the analysis of dynamic biomarkers in living animals. Furthermore, this work highlights critical differences in molecular dynamics in vitro and in vivo, which have important implications for the use of cultured disease models as surrogates for living tissue.

  4. Urinary excretion of the C5b-9 membrane attack complex of complement is a marker of immune disease activity in autologous immune complex nephritis.

    Science.gov (United States)

    Pruchno, C J; Burns, M M; Schulze, M; Johnson, R J; Baker, P J; Alpers, C E; Couser, W G

    1991-01-01

    The urinary excretion of the C5b-9 membrane attack complex of complement correlates with glomerular deposition of antibody in the passive Heymann nephritis (PHN) model of membranous nephropathy (MN). To determine if this parameter can be correlated with antibody deposition in a model of MN induced by an autologous mechanism and thus more analogous to human MN, the relationship of urinary C5b-9 to ongoing glomerular immune complex formation late in autologous immune complex nephritis (AICN) was studied. Based on urinary C5b-9, the animals were divided into two groups at 12 weeks after induction of AICN, those with persistently high urinary C5b-9 excretion and those in whom urinary excretion of C5b-9 returned to undetectable levels. While all rats developed glomerular deposition of rat IgG and significant proteinuria, high C5b-9 excretors had greater proteinuria and prolonged positive staining for glomerular C3. When normal syngeneic kidneys were transplanted into rats (n = 3) from each group, only those with persistent C5b-9 excretion developed subepithelial immune deposits of rat IgG in the transplanted kidney. As in the PHN model of MN, proteinuria was dissociated widely from urinary C5b-9 excretion, glomerular C3 staining, and evidence of circulating antibody. Thus these findings demonstrate that urinary excretion of C5b-9 serves as an index of on-going immunologic disease activity in the AICN model of MN, while proteinuria does not.

  5. Resistivity soundings and VLF profiles for siting groundwater wells in a fractured basement aquifer in the Arabian Shield, Saudi Arabia

    Science.gov (United States)

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

    2016-04-01

    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.

  6. Membranous nephropathy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000472.htm Membranous nephropathy To use the sharing features on this page, please enable JavaScript. Membranous nephropathy is a kidney disorder that leads to changes ...

  7. Disorders of the erythrocyte membrane

    Directory of Open Access Journals (Sweden)

    Sophia Delicou

    2015-12-01

    Full Text Available Hemolytic anemia due to abnormalities of the erythrocyte membrane comprises an important group of inherited disorders. These include hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis, and the hereditary stomatocytosis syndromes. The erythrocyte membrane skeleton composed of spectrin, actin, and several other proteins is essential for the maintenance of the erythrocyte shape, reversible deformability, and membrane structural integrity in addition to controlling the lateral mobility of integral membrane proteins. These disorders are characterized by clinical and laboratory heterogeneity and, as evidenced by recent molecular studies, by genetic heterogeneity. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and hereditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and hereditary elliptocytosis. The disease severity is primarily dependent on the extent of membrane surface area loss. Treatment with splenectomy is curative in most patients.

  8. Firing membranes

    NARCIS (Netherlands)

    Kappert, Emiel Jan

    2015-01-01

    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

  9. Red blood cell membrane concentration of cis-palmitoleic and cis-vaccenic acids and risk of coronary heart disease

    Science.gov (United States)

    Although previous studies have suggested associations between plasma palmitoleic acid and coronary heart disease (CHD) risk factors, including blood pressure, inflammation, and insulin resistance, little is known about the relation of palmitoleic acid and CHD. This ancillary study of the Physicians'...

  10. Pathology of articular cartilage and synovial membrane from elbow joints with and without degenerative joint disease in domestic cats.

    Science.gov (United States)

    Freire, M; Meuten, D; Lascelles, D

    2014-09-01

    The elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. The macroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia. Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (most severe lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached to the synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even in those cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteochondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesions has not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role. © The Author(s) 2014.

  11. Biological preparation Bactocide trial in the submerged basements of residential constructions and public buildings in Dnipropetrovsk city

    OpenAIRE

    T. M. Kotliarova; N. V. Skubenko; N. A. Shokotko; T. N. Perekopskaya; E. E. Korystina

    2006-01-01

    The research of Bactocide application for the control of larval stage of Culex mosquitoes was carried out in the basements submerged by various waters – ground and domestic ones. High efficiency of the Bactocide was proved by parameters of the larval death, that allows recommending it for the control of the Culex pipiens molestus mosquitoes in submerged basements.

  12. Biological preparation Bactocide trial in the submerged basements of residential constructions and public buildings in Dnipropetrovsk city

    Directory of Open Access Journals (Sweden)

    T. M. Kotliarova

    2006-11-01

    Full Text Available The research of Bactocide application for the control of larval stage of Culex mosquitoes was carried out in the basements submerged by various waters – ground and domestic ones. High efficiency of the Bactocide was proved by parameters of the larval death, that allows recommending it for the control of the Culex pipiens molestus mosquitoes in submerged basements.

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

    NARCIS (Netherlands)

    Nyagwambo, N.L.

    2006-01-01

    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

  14. Influence of basement structures on in situ stresses over the Surat Basin, southeast Queensland

    Science.gov (United States)

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

    2015-07-01

    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.