A5007845859- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- T-cell and B-cell Immunology
- Renal and related cancers
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Chemokine receptors and signaling
- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Central Venous Catheters and Hemodialysis
- HIV Research and Treatment
- Liver Disease Diagnosis and Treatment
- Bone and Dental Protein Studies
- Immunodeficiency and Autoimmune Disorders
- Proteoglycans and glycosaminoglycans research
- Vascular Procedures and Complications
- Renal and Vascular Pathologies
- Connective tissue disorders research
- Metabolism, Diabetes, and Cancer
- Urological Disorders and Treatments
- Diabetes Treatment and Management
- Atherosclerosis and Cardiovascular Diseases
- Platelet Disorders and Treatments
University of Washington
2015-2025
Northwestern University
2024
Isfahan University of Medical Sciences
2023
Seattle University
1999-2023
University of Washington Medical Center
1992-2023
Allen Institute for Immunology
2022
VA Salt Lake City Healthcare System
2022
University of Utah
2022
RELX Group (United States)
2018
Cleveland Clinic Lerner College of Medicine
2016
Endothelial attachment is the initial step in leukocyte recruit- ment into developing atherosclerotic lesions.To determine whether vascular cell adhesion molecule-i (VCAM-1) expres- sion may play a role inflammatory recruitment hu- man lesions, immunohistochemistry was performed with polyclonal rabbit antisera, raised against recom- binant human VCAM-1, on 24 coronary plaques and 11 control segments nonatherosclerotic diffuse intimal thickening from 10 patients.Immunophe- notyping adjacent...
Background —Because the content of specific proteoglycans and apolipoproteins is increased in atherosclerotic plaques vitro studies have suggested a role for mediating plaque apolipoprotein (apo) retention, immunohistochemistry was performed to systematically examine relative locations human atherosclerosis. Methods Results —The spatial relationships versican, biglycan, apoE were compared on 68 coronary artery segments; apoA-I apoB also evaluated an additional 20 segments. Nonatherosclerotic...
There remains a need for robust mouse models of diabetic nephropathy (DN) that mimic key features advanced human DN. The recently developed strain BTBR with the ob/ob leptin-deficiency mutation develops severe type 2 diabetes, hypercholesterolemia, elevated triglycerides, and insulin resistance, but renal phenotype has not been characterized. Here, we show these obese, mice rapidly develop morphologic lesions characteristic both early progressive proteinuria beginning at 4 weeks. Glomerular...
Toll-like receptors (TLR) classically recognize pathogen-associated danger signals but are also activated via endogenous ligands. For evaluation of their role in inflammatory kidney disease, the function TLR was analyzed two mouse models cryoglobulinemic membranoproliferative glomerulonephritis (MPGN; mice transgenic for thymic stromal lymphopoietin [TSLP], with or without deletion Fcgamma receptor IIb). Expression TLR1 through 9 and TLR11 mRNA detectable whole kidneys isolated glomeruli...
Differential expression of cyclin-dependent kinase inhibitors in human glomerular disease: Role podocyte proliferation and maturation.BackgroundNormal podocytes are terminally differentiated quiescent cells. It is not known why fail to proliferate response most forms injury. Proliferation regulated by cell cycle proteins their inhibitors. The Cip/Kip family (CDK) (p21, p27, p57) general prevent inhibiting cyclin-CDK complexes. In the current study, we determined possible role specific CDK...
FSGS is a heterogeneous fibrosing disease of the kidney, cause which remains poorly understood. In most cases, there no effective treatment to halt or retard progression renal failure. Increasing evidence points mitochondrial dysfunction and generation reactive oxygen species in pathogenesis CKD. Autophagy, major intracellular lysosomal degradation system, performs homeostatic functions linked metabolism organelle turnover. We prevented normal autophagic pathways nephrons mice by mutating...
The reversibility of diabetic nephropathy remains controversial. Here, we tested whether replacing leptin could reverse the advanced modeled by leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition renin-angiotensin-aldosterone system (RAAS), resulted in near-complete reversal both structural (mesangial matrix expansion, mesangiolysis, basement membrane thickening, podocyte loss) and functional (proteinuria, accumulation reactive oxygen species) measures nephropathy....
Patients with the immunodeficiency Wiskott-Aldrich syndrome (WAS) frequently develop systemic autoimmunity. Here, we demonstrate that mutation of WAS gene results in B cells are hyperresponsive to cell receptor and Toll-like (TLR) signals vitro, thereby promoting a cell–intrinsic break tolerance. Whereas this defect leads autoantibody production protein–deficient (WASp−/−) mice without overt disease, chimeric which only lineage lacks WASp exhibit severe autoimmunity characterized by...
Systemic lupus erythematosus is a multisystem autoimmune disease characterized by autoantibodies targeting nucleic acid-associated Ags. The endosomal TLRs TLR7 and TLR9 are critical for generation of Abs RNA- or DNA-associated Ags, respectively. In murine models, deletion limits inflammation, whereas exacerbates disease. Whether B cell myeloid TLR7/TLR9 signaling responsible these effects has not been fully addressed. this study, we use chimeric strategy to evaluate the effect cell-intrinsic...
ObjectiveEarly thrombosis (ET) contributes to autogenous arteriovenous fistula (AVF) failure. We studied patients undergoing AVF placement in the Hemodialysis Fistula Maturation Study, a prospective, observational cohort study, using nested case-control analysis identify preoperative and intraoperative predictors of ET.MethodsET cases were compared with controls, who matched for gender, age, diabetes, dialysis status, surgeon volume. ET was defined as diagnosed by physical examination or...
In most forms of renal injury, even those due to a primary glomerular process, the extent tubulointerstitial scarring is critical determinant functional reserve and prognosis. Yet, little known about characteristics interstitial cells that mediate processes chronic injury. this study, tissues from normal kidney (N = 7), nephrectomies removed for allograft rejection 14) pyelonephritis 2), cohort 128 biopsies exhibiting range glomerulopathies injury were characterized with antibodies...
To better understand the role of human equilibrative (hENTs) and concentrative (hCNTs) nucleoside transporters in physiology pharmacology, we investigated regional, cellular, spatial distribution two hCNTs (hCNT1 hCNT2) hENTs (hENT1 hENT2) four tissues. Using situ hybridization immunohistochemical techniques, found that duodenum expressed hCNT1 hCNT2 mRNAs enterocytes hENT1 hENT2 crypt cells. In these cells, hCNT hENT proteins were predominantly localized apical lateral membrane,...
ABSTRACT. As chemokine receptor CCR1 and CCR5 expression on circulating leukocytes is thought to contribute leukocyte recruitment during renal fibrosis, the authors examined effects of unilateral ureteral obstruction (UUO) in mice deficient for or CCR5. Analysis UUO kidneys from CCR1-deficient revealed a reduction interstitial macrophages lymphocytes (35% 55%, respectively) compared with wild-type controls. had reduced mRNA levels kidneys, which correlated CCR5+ T cell infiltrate as...
Studies have shown that certain cells of the glomerular tuft begin to express proteins considered unique other cell types upon injury. Little is known about response parietal epithelial (PEC) To determine whether PECs change their phenotype injury also traditionally podocyte specific, following four models disease were studied: transforming growth factor (TGF)-β1 transgenic mouse model global glomerulosclerosis, adriamycin focal segmental glomerulosclerosis (FSGS), anti-glomerular basement...
Inflammatory pathways are central mechanisms in diabetic kidney disease (DKD). Serum amyloid A (SAA) is increased by chronic inflammation, but SAA has not been previously evaluated as a potential DKD mediator. The aims of this study were to determine whether human and corresponding mouse models assess effects on podocyte inflammatory responses. was the plasma people with characterized overt proteinuria inversely correlated estimated glomerular filtration rate (creatinine-based CKD-EPI). also...
Abstract. Osteopontin is a secreted phosphoprotein that expressed by normal kidney, and has been associated with number of functions including cell adhesion, migration, signaling, biomineralization. Although there vast literature detailing osteopontin localization in various rodent models both development disease, this article presents the first comprehensive description human kidney. In study, immunohistochemistry, immunoelectron microscopy, situ hybridization, Northern blotting are used to...
ABSTRACT. Slowly progressive renal injury is the major cause for ESRD. The model of immune complex glomerulonephritis in autoimmune MRL<sup>lpr/lpr</sup> mice was used to evaluate whether chemokine receptor CCR1 blockade late disease course can affect progression failure. Mice were treated with subcutaneous injections either vehicle or BX471, a nonpeptide antagonist, three times week from 20 24 age. BX471 improved blood urea nitrogen levels (BX471, 35.1 ± 5.3; vehicle, 73.1 39.6 mg/dl;...
Abstract. Crescents are morphologic manifestations of severe glomerular injury. Several chemokines and their receptors have been demonstrated to be involved in animal models crescentic glomerulonephritis (cGN) potential targets for therapeutic interventions. Therefore, the expression monocyte chemoattractant protein-1 (MCP-1), its receptor chemokine 2B (CCR2B), CCR5 human cGN was studied. MCP-1 CCR2B mRNA evaluated, by situ hybridization, serial sections 23 renal biopsies from patients with...