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Article: Podocyte

Veron, Delma / Aggarwal, Pardeep K / Li, Qi / Moeckel, Gilbert / Kashgarian, Michael / Tufro, Alda

2022 Volume 12, Page(s) 788886

Abstract: Vascular endothelial growth factor-a (VEGF-A) and nitric oxide (NO) are essential for glomerular filtration barrier homeostasis, and are dysregulated in diabetic kidney disease (DKD). While NO availability is consistently low in diabetes, both high and ... ...

Abstract	Vascular endothelial growth factor-a (VEGF-A) and nitric oxide (NO) are essential for glomerular filtration barrier homeostasis, and are dysregulated in diabetic kidney disease (DKD). While NO availability is consistently low in diabetes, both high and low VEGF-A have been reported in patients with DKD. Here we examined the effect of inducible podocyte
Language	English
Publishing date	2022-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.788886
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Article ; Online: The contribution of quantitative techniques including morphometry to renal diagnosis.

Kashgarian, Michael

Ultrastructural pathology

2006 Volume 30, Issue 5, Page(s) 339–343

Abstract: The use of quantitative techniques in diagnostic renal pathology has not been utilized fully because of the relative inaccessibility and complexity of using statistically valid stereologic techniques. The introduction of digital image capture and ... ...

Abstract	The use of quantitative techniques in diagnostic renal pathology has not been utilized fully because of the relative inaccessibility and complexity of using statistically valid stereologic techniques. The introduction of digital image capture and computer-assisted image analysis has opened a new door to the analysis of renal biopsies. The potential of quantitative information to give greater prognostic information or better insight into the pathogenesis of many of these lesions is yet to be completely elucidated. Digital imaging and the advent of virtual microscopy should open new avenues of investigation into the pathogenesis of renal disease using clinically obtained renal biopsy material.
MeSH term(s)	Biopsy ; Female ; Glomerular Basement Membrane/ultrastructure ; Humans ; Image Processing, Computer-Assisted ; Kidney Diseases/diagnosis ; Kidney Diseases/etiology ; Male ; Pathology/methods ; Prognosis ; Reference Values
Language	English
Publishing date	2006-09
Publishing country	England
Document type	Journal Article
ZDB-ID	603269-2
ISSN	1521-0758 ; 0191-3123
ISSN (online)	1521-0758
ISSN	0191-3123
DOI	10.1080/01913120600932537
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Article: Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis.

Wilson, Parker C / Kashgarian, Michael / Moeckel, Gilbert

Clinical kidney journal

2017 Volume 11, Issue 2, Page(s) 207–218

Abstract: Background: This study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis.: Methods: Baseline characteristics, initial (: Results: A total of 218 patients had follow- ... ...

Abstract	Background: This study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis. Methods: Baseline characteristics, initial ( Results: A total of 218 patients had follow-up and Class IV had worse renal survival, especially in patients with active and chronic glomerular lesions {relative to non-IV; Class IV-A: hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.41-2.04], Class IV-AC: HR 5.02 [95% CI 2.70-9.36]}. Interstitial inflammation grade [relative to interstitial inflammation <5%; interstitial inflammation 5-25%: HR 2.36 (95% CI 1.13-4.91), interstitial inflammation 25-50%: HR 3.84 (95% CI 1.53-9.62), interstitial inflammation >50%: HR 7.67 (95% CI 3.75-15.67)] and increased interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA <5%; IFTA 5-25%: HR 3.93 (95% CI 1.58-9.75), IFTA 25-50%: HR 4.01 (95% CI 1.37-11.70), IFTA >50%: HR 13.99 (95% CI 4.91-39.83)] predicted worse renal survival among all patients and those with Class IV on initial and repeat biopsy ( Conclusions: Interstitial inflammation and IFTA independently affect renal survival and grading these lesions stratifies risk within the International Society of Nephrology and Renal Pathology Society classification of lupus nephritis.
Language	English
Publishing date	2017-08-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfx093
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Article ; Online: Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis.

Melchinger, Hannah / Calderon-Gutierrez, Frida / Obeid, Wassim / Xu, Leyuan / Shaw, Melissa M / Luciano, Randy L / Kuperman, Michael / Moeckel, Gilbert W / Kashgarian, Michael / Wilson, F Perry / Parikh, Chirag R / Moledina, Dennis G

Clinical journal of the American Society of Nephrology : CJASN

2022 Volume 17, Issue 9, Page(s) 1284–1292

Abstract: Background and objectives: Uromodulin, produced exclusively in the kidney's thick ascending limb, is a biomarker of kidney tubular health. However, the relationship between urine uromodulin and histologic changes in the kidney tubulointerstitium has not ...

Abstract	Background and objectives: Uromodulin, produced exclusively in the kidney's thick ascending limb, is a biomarker of kidney tubular health. However, the relationship between urine uromodulin and histologic changes in the kidney tubulointerstitium has not been characterized. In this study, we test the association of urine uromodulin with kidney histologic findings in humans and mice. Design, setting, participants, & measurements: We investigated the independent association of urine uromodulin measured at the time of kidney biopsy with histologic features in 364 participants at two academic medical centers from 2015 to 2018 using multivariable linear regression models. This relationship was further examined by comparison of uromodulin staining in murine models of kidney fibrosis and repair. Results: We found urine uromodulin to be correlated with serum creatinine (rho=-0.43; Conclusions: Higher urine uromodulin is independently associated with lower tubulointerstitial fibrosis in both human kidney biopsies and a mouse model of fibrosis. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_08_10_CJN04360422.mp3.
MeSH term(s)	Humans ; Mice ; Animals ; Uromodulin/urine ; Creatinine ; Kidney/pathology ; Kidney Diseases/pathology ; Fibrosis ; Biomarkers ; Atrophy/pathology ; Albumins
Chemical Substances	Uromodulin ; Creatinine (AYI8EX34EU) ; Biomarkers ; Albumins
Language	English
Publishing date	2022-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.04360422
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Article ; Online: Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.

Moledina, Dennis G / Obeid, Wassim / Smith, Rex N / Rosales, Ivy / Sise, Meghan E / Moeckel, Gilbert / Kashgarian, Michael / Kuperman, Michael / Campbell, Kirk N / Lefferts, Sean / Meliambro, Kristin / Bitzer, Markus / Perazella, Mark A / Luciano, Randy L / Pober, Jordan S / Cantley, Lloyd G / Colvin, Robert B / Wilson, F Perry / Parikh, Chirag R

The Journal of clinical investigation

2024 Volume 134, Issue 6

MeSH term(s)	Humans ; Nephritis, Interstitial/diagnosis ; Biomarkers ; Acute Disease ; Chemokine CXCL9
Chemical Substances	Biomarkers ; CXCL9 protein, human ; Chemokine CXCL9
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI180583
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Article ; Online: A Human MSH6 Germline Variant Associated With Systemic Lupus Erythematosus Induces Lupus-like Disease in Mice.

Meas, Rithy / Nititham, Joanne / Taylor, Kimberly E / Maher, Stephen / Clairmont, Kaylyn / Carufe, Kelly E W / Kashgarian, Michael / Nottoli, Timothy / Cheong, Ana / Nagel, Zachary D / Gaffney, Patrick M / Criswell, Lindsey A / Sweasy, Joann B

ACR open rheumatology

2022 Volume 4, Issue 9, Page(s) 760–770

Abstract: Objective: To determine if single-nucleotide polymorphisms (SNPs) in DNA repair genes are enriched in individuals with systemic lupus erythematosus (SLE) and if they are sufficient to confer a disease phenotype in a mouse model.: Methods: Human exome ...

Abstract	Objective: To determine if single-nucleotide polymorphisms (SNPs) in DNA repair genes are enriched in individuals with systemic lupus erythematosus (SLE) and if they are sufficient to confer a disease phenotype in a mouse model. Methods: Human exome chip data of 2499 patients with SLE and 1230 healthy controls were analyzed to determine if variants in 10 different mismatch repair genes (MSH4, EXO1, MSH2, MSH6, MLH1, MSH3, POLH, PMS2, ML3, and APEX2) were enriched in individuals with SLE. A mouse model of the MSH6 SNP, which was found to be enriched in individuals with SLE, was created using CRISPR/Cas9 gene targeting. Wildtype mice and mice heterozygous and homozygous for the MSH6 variant were then monitored for 2 years for the development of autoimmune phenotypes, including the presence of high levels of antinuclear antibodies (ANA). Additionally, somatic hypermutation frequencies and spectra of the intronic region downstream of the V Results: Based on the human exome chip data, the MSH6 variant (rs63750897, p.Ser503Cys) is enriched among patients with SLE versus controls after we corrected for ancestry (odds ratio = 8.39, P = 0.0398). Mice homozygous for the MSH6 variant (Msh6 Conclusion: An MSH6 mutation that is enriched in humans diagnosed with lupus was identified. Mice harboring this Msh6 mutation develop increased autoantibodies and an inflammatory lung disease. These results suggest that the human MSH6 variant is linked to the development of SLE.
Language	English
Publishing date	2022-06-16
Publishing country	United States
Document type	Journal Article
ISSN	2578-5745
ISSN (online)	2578-5745
DOI	10.1002/acr2.11471
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Article: Are there New Activity Markers of Glomerular Inflammation? A Renal Pathologist's View

Kashgarian, Michael

Kidney and Blood Pressure Research

2008 Volume 21, Issue 2-4, Page(s) 215–216

Institution	Department of Pathology and Biology, Yale University School of Medicine, New Haven, Conn., USA
Keywords	Interstitial fibrosis ; Tubular atrophy ; Glomerular inflammation ; Activity markers
Language	English
Publishing date	2008-11-13
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Plenary Lectures
ZDB-ID	1326018-2
ISSN	1423-0143 ; 1420-4096
ISSN (online)	1423-0143
ISSN	1420-4096
DOI	10.1159/000025858
Database	Karger publisher's database

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Article ; Online: B cell-intrinsic TLR9 expression is protective in murine lupus.

Tilstra, Jeremy S / John, Shinu / Gordon, Rachael A / Leibler, Claire / Kashgarian, Michael / Bastacky, Sheldon / Nickerson, Kevin M / Shlomchik, Mark J

The Journal of clinical investigation

2020 Volume 130, Issue 6, Page(s) 3172–3187

Abstract: Toll-like receptor 9 (TLR9) is a regulator of disease pathogenesis in systemic lupus erythematosus (SLE). Why TLR9 represses disease while TLR7 and MyD88 have the opposite effect remains undefined. To begin to address this question, we created 2 alleles ... ...

Abstract	Toll-like receptor 9 (TLR9) is a regulator of disease pathogenesis in systemic lupus erythematosus (SLE). Why TLR9 represses disease while TLR7 and MyD88 have the opposite effect remains undefined. To begin to address this question, we created 2 alleles to manipulate TLR9 expression, allowing for either selective deletion or overexpression. We used these to test cell type-specific effects of Tlr9 expression on the regulation of SLE pathogenesis. Notably, Tlr9 deficiency in B cells was sufficient to exacerbate nephritis while extinguishing anti-nucleosome antibodies, whereas Tlr9 deficiency in dendritic cells (DCs), plasmacytoid DCs, and neutrophils had no discernable effect on disease. Thus, B cell-specific Tlr9 deficiency unlinked disease from autoantibody production. Critically, B cell-specific Tlr9 overexpression resulted in ameliorated nephritis, opposite of the effect of deleting Tlr9. Our findings highlight the nonredundant role of B cell-expressed TLR9 in regulating lupus and suggest therapeutic potential in modulating and perhaps even enhancing TLR9 signals in B cells.
MeSH term(s)	Animals ; Antibody Formation ; Autoantibodies/genetics ; Autoantibodies/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Disease Models, Animal ; Gene Expression Regulation/immunology ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/pathology ; Lupus Erythematosus, Systemic/prevention & control ; Mice ; Mice, Knockout ; Signal Transduction/genetics ; Signal Transduction/immunology ; Toll-Like Receptor 9/deficiency ; Toll-Like Receptor 9/immunology
Chemical Substances	Autoantibodies ; Tlr9 protein, mouse ; Toll-Like Receptor 9
Language	English
Publishing date	2020-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI132328
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Book ; Online: Geochemistry of foraminifera from sediment cores of the central California margin, supplementary data to: van Geen, A; Fairbanks, Richard G; Dartnell, P; McGann, Mary L; Gardner, James V; Kashgarian, M (1996): Ventilation changes in the northeast Pacific during the last deglaciation. Paleoceanography, 11(5), 519-528

van Geen, A / Dartnell, P / Fairbanks, Richard G / Gardner, James V / Kashgarian, M / McGann, Mary L

1996

Abstract: ... at 800 and 1600 m depth to argue that the depth of ventilation shifted repeatedly ... ventilation at 800 m, ventilation was enhanced at 1600 m depth, and vice versa. This pronounced depth ...

Abstract	Under present climate conditions, convection at high latitudes of the North Pacific is restricted to shallower depths than in the North Atlantic. To what extent this asymmetry between the two ocean basins was maintained over the past 20 kyr is poorly known because there are few unambiguous proxy records of ventilation from the North Pacific. We present new data for two sediment cores from the California margin at 800 and 1600 m depth to argue that the depth of ventilation shifted repeatedly in the northeast Pacific over the course of deglaciation. The evidence includes benthic foraminiferal Cd/Ca, 18O/16O, and 13C/12C data as well as radiocarbon age differences between benthic and planktonic foraminifera. A number of features in the shallower of the two cores, including an interval of laminated sediments, are consistent with changes in ventilation over the past 20 kyr suggested by alternations between laminated and bioturbated sediments in the Santa Barbara Basin and the Gulf of California [Keigwin and Jones, 1990 doi:10.1029/PA005i006p01009; Kennett and Ingram, 1995 doi:10.1038/377510a0; Behl and Kennett, 1996 doi:10.1038/379243a0]. Data from the deeper of the two California margin cores suggest that during times of reduced ventilation at 800 m, ventilation was enhanced at 1600 m depth, and vice versa. This pronounced depth dependence of ventilation needs to be taken into account when exploring potential teleconnections between the North Pacific and the North Atlantic.
Language	English
Dates of publication	1996-9999
Size	Online-Ressource
Publisher	PANGAEA - Data Publisher for Earth & Environmental Science
Publishing place	Bremen/Bremerhaven
Document type	Book ; Online
Note	This dataset is supplement to doi:10.1029/96PA01860
DOI	10.1594/PANGAEA.729962
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article: Are there new activity markers of glomerular inflammation? A renal pathologist's view.

Kashgarian, M

Kidney & blood pressure research

1998 Volume 21, Issue 2-4, Page(s) 215–216

MeSH term(s)	Animals ; Biomarkers ; Glomerulonephritis/metabolism ; Glomerulonephritis/pathology ; Humans
Chemical Substances	Biomarkers
Language	English
Publishing date	1998
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1326018-2
ISSN	1423-0143 ; 1420-4096
ISSN (online)	1423-0143
ISSN	1420-4096
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