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https://www.readbyqxmd.com/read/29644057/clinical-and-pathological-phenotype-of-genetic-causes-of-focal-segmental-glomerulosclerosis-in-adults
#1
Nicola Lepori, Ladan Zand, Sanjeev Sethi, Gema Fernandez-Juarez, Fernando C Fervenza
Focal segmental glomerulosclerosis (FSGS) is a histologic lesion resulting from a variety of pathogenic processes that cause injury to the podocytes. Recently, mutations in more than 50 genes expressed in podocyte or glomerular basement membrane were identified as causing genetic forms of FSGS, the majority of which are characterized by onset in childhood. The prevalence of adult-onset genetic FSGS is likely to be underestimated and its clinical and histological features have not been clearly described. A small number of studies of adult-onset genetic FSGS showed that there is heterogeneity in clinical and histological findings, with a presentation ranging from sub-nephrotic proteinuria to full nephrotic syndrome...
April 2018: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29642511/effect-of-pinocembrin-isolated-from-mexican-brown-propolis-on-diabetic-nephropathy
#2
Jessica Granados-Pineda, Norma Uribe-Uribe, Patricia García-López, María Del Pilar Ramos-Godinez, J Fausto Rivero-Cruz, Jazmin Marlen Pérez-Rojas
Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds, wounds, rheumatism, heart disease and diabetes. Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are few alternatives. The present study aimed to determine the chemical composition of three propolis samples collected in Chihuahua, Durango and Zacatecas and to evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo...
April 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29615804/combining-streptozotocin-and-unilateral-nephrectomy-is-an-effective-method-for-inducing-experimental-diabetic-nephropathy-in-the-resistant-c57bl-6j-mouse-strain
#3
Melissa Uil, Angelique M L Scantlebery, Loes M Butter, Per W B Larsen, Onno J de Boer, Jaklien C Leemans, Sandrine Florquin, Joris J T H Roelofs
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Animal models are essential tools for designing new strategies to prevent DN. C57Bl/6 (B6) mice are widely used for transgenic mouse models, but are relatively resistant to DN. This study aims to identify the most effective method to induce DN in a type 1 (T1D) and a type 2 diabetes (T2D) model in B6 mice. For T1D-induced DN, mice were fed a control diet, and randomised to streptozotocin (STZ) alone, STZ+unilateral nephrectomy (UNx), or vehicle/sham...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29611334/conditional-ablation-of-the-prorenin-receptor-in-nephron-progenitor-cells-results-in-developmental-programming-of-hypertension
#4
Renfang Song, Laura Kidd, Adam Janssen, Ihor V Yosypiv
Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells (NPCs) of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump V-ATPase. Previously, we demonstrated that conditional ablation of the PRR in Six2+ NPCs in mice (Six2PRR -/- ) causes early neonatal death. Here, we identified genes that are regulated by PRR in Six2+ NPCs FACS-isolated from Six2PRR -/- and control kidneys on embryonic day E15...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29610978/the-relationship-between-the-thickness-of-glomerular-basement-membrane-and-renal-outcomes-in-patients-with-diabetic-nephropathy
#5
Junlin Zhang, Yiting Wang, Pramesh Gurung, Tingli Wang, Li Li, Rui Zhang, Hanyu Li, Ruikun Guo, Qianqian Han, Jie Zhang, Song Lei, Fang Liu
AIMS: Glomerular basement membrane (GBM) thickening is considered as one of the earliest detectable pathological features of diabetic nephropathy (DN). However, whether the thickness of GBM will impact the prognosis of DN remains largely unknown. Our aim was to explore the relationship between thickness of GBM and DN progression in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 118 patients with T2DM and biopsy-proven DN who received follow-up for at least 1 year were recruited...
April 2, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29602372/-the-pathology-of-renal-transplants
#6
Eduardo Vazquez Martul
In order to make an objective assessment of the histopathology of a renal biopsy during a kidney transplant, all the various elements involved in the process must be understood. It is important to know the characteristics of the donor organ, especially if the donor is older than 65. The histopathological features of the donor biopsy, especially its vascular status, are often related to an initial poor function of the transplanted kidney. The T lymphocyte inflammatory response is characteristic in acute cellular rejection; the degree of tubulitis, together with the amount of affected parenchyme, are important factors...
April 2018: Revista Española de Patología
https://www.readbyqxmd.com/read/29588430/an-engineered-complement-factor-h-construct-for-treatment-of-c3-glomerulopathy
#7
Yi Yang, Harriet Denton, Owen R Davies, Kate Smith-Jackson, Heather Kerr, Andrew P Herbert, Paul N Barlow, Matthew C Pickering, Kevin J Marchbank
Background C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for C3G remain limited. Complement factor H (FH) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of FH makes generation of full-length FH far from trivial. We previously generated a mini-FH construct, with FH short consensus repeats 1-5 linked to repeats 18-20 (FH1-5^18-20 ), that was effective in experimental C3G...
March 27, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29580581/acute-kidney-injury-and-progression-of-diabetic-kidney-disease
#8
REVIEW
Samuel Mon-Wei Yu, Joseph V Bonventre
Diabetic kidney disease, commonly termed diabetic nephropathy (DN), is the most common cause of end-stage kidney disease (ESKD) worldwide. The characteristic histopathology of DN includes glomerular basement membrane thickening, mesangial expansion, nodular glomerular sclerosis, and tubulointerstitial fibrosis. Diabetes is associated with a number of metabolic derangements, such as reactive oxygen species overproduction, hypoxic state, mitochondrial dysfunction, and inflammation. In the past few decades, our knowledge of DN has advanced considerably although much needs to be learned...
March 2018: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29559657/early-and-late-scanning-electron-microscopy-findings-in-diabetic-kidney-disease
#9
Sara Conti, Norberto Perico, Rubina Novelli, Camillo Carrara, Ariela Benigni, Giuseppe Remuzzi
Diabetic nephropathy (DN), the single strongest predictor of mortality in patients with type 2 diabetes, is characterized by initial glomerular hyperfiltration with subsequent progressive renal function loss with or without albuminuria, greatly accelerated with the onset of overt proteinuria. Experimental and clinical studies have convincingly shown that early interventions retard disease progression, while treatment if started late in the disease course seldom modifies the slope of GFR decline. Here we assessed whether the negligible renoprotection afforded by drugs in patients with proteinuric DN could be due to loss of glomerular structural integrity, explored by scanning electron microscopy (SEM)...
March 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29551517/alport-syndrome-a-unified-classification-of-genetic-disorders-of-collagen-iv-%C3%AE-345-a-position-paper-of-the-alport-syndrome-classification-working-group
#10
Clifford E Kashtan, Jie Ding, Guido Garosi, Laurence Heidet, Laura Massella, Koichi Nakanishi, Kandai Nozu, Alessandra Renieri, Michelle Rheault, Fang Wang, Oliver Gross
Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from microscopic hematuria to progressive renal disease leading to ESRD, and with extrarenal manifestations such as sensorineural deafness and ocular anomalies. The existing nomenclature for these conditions is confusing and can delay institution of appropriate nephroprotective therapy...
March 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29549365/fyve-domain-containing-protein-zfyve28-regulates-egfr-signaling-in-podocytes-but-is-not-critical-for-the-function-of-filtration-barrier-in-mice
#11
Sonia Zambrano, Patricia Q Rodriguez, Jing Guo, Katja Möller-Hackbarth, Angelina Schwarz, Jaakko Patrakka
The kidney ultrafiltration barrier is formed of endothelial cells, the glomerular basement membrane and podocytes. Podocytes have a central role in normal physiology and disease pathogenesis of the glomerulus. Signaling through epidermal growth factor receptor (EGFR) in podocytes mediates development of many glomerular disease processes. In this work, we have identified zinc finger FYVE-type containing 28 (ZFYVE28) as a novel highly podocyte-enriched gene. We localize ZFYVE28 in podocyte foot processes in adult kidney...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29547404/halogens-are-key-cofactors-in-building-of-collagen-iv-scaffolds-outside-the-cell
#12
Kyle L Brown, Billy G Hudson, Paul A Voziyan
PURPOSE OF REVIEW: The purpose of this review is to highlight recent advances in understanding the molecular assembly of basement membranes, as exemplified by the glomerular basement membrane (GBM) of the kidney filtration apparatus. In particular, an essential role of halogens in the basement membrane formation has been discovered. RECENT FINDINGS: Extracellular chloride triggers a molecular switch within non collagenous domains of collagen IV that induces protomer oligomerization and scaffold assembly outside the cell...
March 15, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29534626/nf-%C3%AE%C2%BAb-signaling-pathway-enhanced-complement-activation-mediates-renal-injury-in-trichloroethylene-sensitized-mice
#13
Min Liu, Hui Wang, Jiaxiang Zhang, Xiaodong Yang, Bodong Li, Changhao Wu, Qixing Zhu
Both NF-κB pathway and complement activation appear to be involved in kidney damage induced by trichloroethylene (TCE). However, any relationship between these two systems has not yet been established. The present study aimed to clarify the role of NF-κB in complement activation and renal injury in TCE-sensitized BALB/c mice. Mice were sensitized by an initial subcutaneous injection and repeated focal applications of TCE to dorsal skin at specified timepoints. NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was injected (intraperitoneal) before the final two focal TCE challenges...
December 2018: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29534211/genetic-variants-in-the-lama5-gene-in-pediatric-nephrotic-syndrome
#14
Daniela A Braun, Jillian K Warejko, Shazia Ashraf, Weizhen Tan, Ankana Daga, Ronen Schneider, Tobias Hermle, Tilman Jobst-Schwan, Eugen Widmeier, Amar J Majmundar, Makiko Nakayama, David Schapiro, Jia Rao, Johanna Magdalena Schmidt, Charlotte A Hoogstraten, Hannah Hugo, Sevcan A Bakkaloglu, Jameela A Kari, Sherif El Desoky, Ghaleb Daouk, Shrikant Mane, Richard P Lifton, Shirlee Shril, Friedhelm Hildebrandt
Background: Nephrotic syndrome (NS), a chronic kidney disease, is characterized by significant loss of protein in the urine causing hypoalbuminemia and edema. In general, ∼15% of childhood-onset cases do not respond to steroid therapy and are classified as steroid-resistant NS (SRNS). In ∼30% of cases with SRNS, a causative mutation can be detected in one of 44 monogenic SRNS genes. The gene LAMA5 encodes laminin-α5, an essential component of the glomerular basement membrane. Mice with a hypomorphic mutation in the orthologous gene Lama5 develop proteinuria and hematuria...
March 9, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29530752/a-unique-evolution-of-the-kidney-phenotype-in-a-patient-with-autosomal-recessive-alport-syndrome
#15
Gisella Vischini, Meghan E Kapp, Ferrin C Wheeler, Laszlo Hopp, Agnes B Fogo
Alport syndrome is due to mutations in one of the genes encoding (α3,4,5) type IV collagen resulting in defective type IV collagen, a key component of the glomerular basement membrane (GBM). The GBM is initially thin, and with ongoing remodeling, develops a thickened basket-woven appearance. We report a unique case of a 9-year-old boy who was biopsied for hematuria and proteinuria, diagnosed as IgA nephropathy, with normal GBM appearance and thickness. Due to a family history of hematuria and chronic kidney disease, he subsequently underwent genetic evaluation and a mutation of α3 type IV collagen (COL4A3) was detected...
March 9, 2018: Human Pathology
https://www.readbyqxmd.com/read/29526710/a-split-luciferase-based-trimer-formation-assay-as-a-high-throughput-screening-platform-for-therapeutics-in-alport-syndrome
#16
Kohei Omachi, Misato Kamura, Keisuke Teramoto, Haruka Kojima, Tsubasa Yokota, Shota Kaseda, Jun Kuwazuru, Ryosuke Fukuda, Kosuke Koyama, Shingo Matsuyama, Keishi Motomura, Tsuyoshi Shuto, Mary Ann Suico, Hirofumi Kai
Alport syndrome is a hereditary glomerular disease caused by mutation in type IV collagen α3-α5 chains (α3-α5(IV)), which disrupts trimerization, leading to glomerular basement membrane degeneration. Correcting the trimerization of α3/α4/α5 chain is a feasible therapeutic approach, but is hindered by lack of information on the regulation of intracellular α(IV) chain and the absence of high-throughput screening (HTS) platforms to assess α345(IV) trimer formation. Here, we developed sets of split NanoLuc-fusion α345(IV) proteins to monitor α345(IV) trimerization of wild-type and clinically associated mutant α5(IV)...
February 21, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29515303/dense-deposit-disease-involving-c3-and-c4d-deposits
#17
M Vankalakunti, R Augustine, R Jangamani, V Siddini, R Bonu, K Babu, S H Ballal
Dense deposit disease (DDD), earlier called Type II membranoproliferative glomerulonephritis is distinct disease having frequent relapses reaching end-stage kidney disease by 10-year in up to 50%-60% of cases and high recurrence rate in the allograft. The term DDD is derived from its distinctive ribbon-like osmiophilic deposits in the lamina densa of glomerular basement membrane by electron microscopy. Pathogenetically, alternate pathway dysfunction leads to this disease, which is diagnosed by ultrastructure...
January 2018: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/29510921/the-clinical-and-immunologic-features-of-patients-with-combined-anti-gbm-disease-and-castleman-disease
#18
Qiu-Hua Gu, Xiao-Yu Jia, Shui-Yi Hu, Su-Xia Wang, Wan-Zhong Zou, Zhao Cui, Ming-Hui Zhao
Patients with both anti-glomerular basement membrane (anti-GBM) disease and Castleman disease have been rarely reported. In this study, we report 3 patients with this combination. They had immunologic features similar to patients with classic anti-GBM disease. Sera from the 3 patients recognized the noncollagenous (NC) domain of the α3 chain of type IV collagen (α3(IV)NC1) and its 2 major epitopes, EA and EB. All 4 immunogloblin G (IgG) subclasses against α3(IV)NC1 were detectable, with predominance of IgG1...
March 3, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29508174/silencing-of-cxcl12-performs-a-protective-effect-on-c5b-9-induced-injury-in-podocytes
#19
Wengang Sha, Lei Shen, Ling Zhou, Deyu Xu, Jing Yang, Guoyuan Lu
PURPOSE: Podocytes, terminal differentiation cell in glomerulu, are crucial to kidney-related diseases such as membranous nephropathy (MN). MN is characterized by podocyte injury and glomerular basement membrane thickening. This paper focused to investigate the expression of chemokine (C-X-C motif) ligand 12 (CXCL12) in MN patients and its possible role in podocyte injury. METHODS: Through the enzyme-linked immunosorbent assay, CXCL12 level in the serum and urine of MN patients was examined...
March 5, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29506630/human-podocytes-responses-to-alternatively-spliced-extra-domain-a-fibronectin-in-culture
#20
Tarunkumar Hemraj Madne, Mark Edward Carl Dockrell
The interactions of the extracellular matrix (ECM) proteins with cells strongly regulate cell behaviour. The glomerular basement membrane (GBM) is a dynamic structure made up of protein secreted by endothelial cells and podocyte. These proteins could regulate the behaviour of these cells in health and diseases. Extra Domain A + Fn (EDA+Fn) is an alternatively spliced form of Fibronectin (Fn) recently identified in GBM and a recognised marker of various pathologies. In this study for the first time, we have investigated the responses of human podocytes cultured on different composition of GBM proteins which are cellular Fn (EDA+), plasma Fn (EDA-) and collagen IV...
February 28, 2018: Cellular and Molecular Biology
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