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Article ; Online: Vascularized Plexus Allotransplantation: A New Hope in Brachial Plexus Palsy?

Farkash, Evan A / Leonard, David A

2018 Volume 103, Issue 1, Page(s) 17–18

MeSH term(s)	Animals ; Brachial Plexus ; Brachial Plexus Neuropathies ; Paralysis ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew
Language	English
Publishing date	2018-07-26
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000002388
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 509: Show issues

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Article ; Online: Authors' Reply.

Farkash, Evan A / Wilson, Allecia M / Jentzen, Jeffrey M

Journal of the American Society of Nephrology : JASN

2020 Volume 31, Issue 9, Page(s) 2225–2226

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-08-12
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2020060847
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Zs.A 3344: Show issues

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Article ; Online: Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2.

Farkash, Evan A / Wilson, Allecia M / Jentzen, Jeffrey M

Journal of the American Society of Nephrology : JASN

2020 Volume 31, Issue 8, Page(s) 1683–1687

Abstract: Background: A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ... ...

Abstract	Background: A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2. Methods: We performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells. Results: Light microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 Conclusions: The presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.
MeSH term(s)	Acute Kidney Injury/complications ; Acute Kidney Injury/mortality ; Aortic Dissection/surgery ; Autopsy ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/mortality ; Epithelial Cells/pathology ; Humans ; Kidney Tubules/pathology ; Kidney Tubules/ultrastructure ; Kidney Tubules/virology ; Male ; Middle Aged ; Nephritis/physiopathology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/mortality ; Prognosis ; Respiratory Insufficiency ; Retrospective Studies ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-05-05
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2020040432
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Article: Authors' Reply

Farkash, Evan A / Wilson, Allecia M / Jentzen, Jeffrey M

J Am Soc Nephrol

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #836029
Database	COVID19

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Article ; Online: A case of cryocrystalglobulinemia.

Avedschmidt, Sarah E / Farkash, Evan A / Yamada, Chisa

Transfusion

2016 Volume 56, Issue 7, Page(s) 1678–1679

Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.13528
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Zs.A 284: Show issues

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Article: Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2

Farkash, Evan A / Wilson, Allecia M / Jentzen, Jeffrey M

J Am Soc Nephrol

Abstract: BACKGROUND: A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ARF, ...

Abstract	BACKGROUND: A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2. METHODS: We performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells. RESULTS: Light microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 µm in diameter and had an envelope studded with crown-like, electron-dense spikes. Vacuoles contained double-membrane vesicles suggestive of partially assembled virus. CONCLUSIONS: The presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #186288
Database	COVID19

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Article ; Online: Double Trouble.

Smith, Christopher / Dhaliwal, Gurpreet / Saint, Sanjay / Farkash, Evan A / Garg, Puneet

The New England journal of medicine

2019 Volume 381, Issue 19, Page(s) 1854–1860

MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Anti-Glomerular Basement Membrane Disease/complications ; Anti-Glomerular Basement Membrane Disease/diagnosis ; Antibodies, Antineutrophil Cytoplasmic/blood ; Arthralgia/etiology ; Autoantibodies/blood ; Biopsy ; Cough/etiology ; Diagnosis, Differential ; Fatigue/etiology ; Fever/etiology ; Humans ; Kidney/diagnostic imaging ; Kidney/pathology ; Male ; Middle Aged ; Pleural Effusion/diagnostic imaging ; Radiography, Thoracic
Chemical Substances	Anti-Bacterial Agents ; Antibodies, Antineutrophil Cytoplasmic ; Autoantibodies ; antiglomerular basement membrane antibody
Language	English
Publishing date	2019-11-06
Publishing country	United States
Document type	Case Reports ; Clinical Conference ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcps1810654
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Article: Encapsulated Allografts Preclude Host Sensitization and Promote Ovarian Endocrine Function in Ovariectomized Young Rhesus Monkeys and Sensitized Mice.

Day, James R / Flanagan, Colleen L / David, Anu / Hartigan-O'Connor, Dennis J / Garcia de Mattos Barbosa, Mayara / Martinez, Michele L / Lee, Charles / Barnes, Jenna / Farkash, Evan / Zelinski, Mary / Tarantal, Alice / Cascalho, Marilia / Shikanov, Ariella

Bioengineering (Basel, Switzerland)

2023 Volume 10, Issue 5

Abstract: Transplantation of allogeneic donor ovarian tissue holds great potential for female cancer survivors who often experience premature ovarian insufficiency. To avoid complications associated with immune suppression and to protect transplanted ovarian ... ...

Abstract	Transplantation of allogeneic donor ovarian tissue holds great potential for female cancer survivors who often experience premature ovarian insufficiency. To avoid complications associated with immune suppression and to protect transplanted ovarian allografts from immune-mediated injury, we have developed an immunoisolating hydrogel-based capsule that supports the function of ovarian allografts without triggering an immune response. Encapsulated ovarian allografts implanted in naïve ovariectomized BALB/c mice responded to the circulating gonadotropins and maintained function for 4 months, as evident by regular estrous cycles and the presence of antral follicles in the retrieved grafts. In contrast to non-encapsulated controls, repeated implantations of encapsulated mouse ovarian allografts did not sensitize naïve BALB/c mice, which was confirmed with undetectable levels of alloantibodies. Further, encapsulated allografts implanted in hosts previously sensitized by the implantation of non-encapsulated allografts restored estrous cycles similarly to our results in naïve recipients. Next, we tested the translational potential and efficiency of the immune-isolating capsule in a rhesus monkey model by implanting encapsulated ovarian auto- and allografts in young ovariectomized animals. The encapsulated ovarian grafts survived and restored basal levels of urinary estrone conjugate and pregnanediol 3-glucuronide during the 4- and 5-month observation periods. We demonstrate, for the first time, that encapsulated ovarian allografts functioned for months in young rhesus monkeys and sensitized mice, while the immunoisolating capsule prevented sensitization and protected the allograft from rejection.
Language	English
Publishing date	2023-05-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering10050550
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Article ; Online: The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope.

Miglioranza Scavuzzi, Bruna / van Drongelen, Vincent / Kaur, Bhavneet / Fox, Jennifer Callahan / Liu, Jianhua / Mesquita-Ferrari, Raquel A / Kahlenberg, J Michelle / Farkash, Evan A / Benavides, Fernando / Miller, Frederick W / Sawalha, Amr H / Holoshitz, Joseph

Communications biology

2022 Volume 5, Issue 1, Page(s) 751

Abstract: The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic ... ...

Abstract	The HLA-DRB103:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB103:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IFN-γ to naïve DRB1*03:01 transgenic mice causes increased serum levels of anti-double stranded DNA antibodies, glomerular immune complex deposition and histopathological renal changes that resemble human lupus nephritis. This study provides evidence for a noncanonical, antigen presentation-independent mechanism of HLA-disease association in SLE and could lay new foundations for our understanding of key molecular mechanisms that trigger and propagate this devastating autoimmune disease.
MeSH term(s)	Alleles ; Animals ; Epitopes/genetics ; Genetic Predisposition to Disease ; HLA-DRB1 Chains/genetics ; Humans ; Interferon-gamma/genetics ; Lupus Erythematosus, Systemic/genetics ; Mice
Chemical Substances	Epitopes ; HLA-DRB1 Chains ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2022-07-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-022-03717-x
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Article ; Online: Inhibition of EZH2 Ameliorates Lupus-Like Disease in MRL/lpr Mice.

Rohraff, Dallas M / He, Ye / Farkash, Evan A / Schonfeld, Mark / Tsou, Pei-Suen / Sawalha, Amr H

Arthritis & rheumatology (Hoboken, N.J.)

2019 Volume 71, Issue 10, Page(s) 1681–1690

Abstract: Objective: We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus-like disease in MRL/ ...

Abstract	Objective: We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus-like disease in MRL/lpr mice. Methods: EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and messenger RNA expression data. Inhibition of EZH2 in MRL/lpr mice was achieved by intraperitoneal 3'-deazaneplanocin (DZNep) administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti-double-stranded DNA (anti-dsDNA) antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed. Results: EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL/lpr mice, inhibition of EZH2 by DZNep was confirmed by significant reduction of EZH2 and H3K27me3 in splenocytes. Inhibiting EZH2 with DZNep treatment before or after disease onset improved survival and significantly reduced anti-dsDNA antibody production. DZNep-treated mice displayed a significant reduction in renal involvement, splenomegaly, and lymphadenopathy. Lymphoproliferation and numbers of double-negative T cells were significantly reduced in DZNep-treated mice. Concentrations of circulating cytokines and chemokines, including tumor necrosis factor, interferon-γ, CCL2, RANTES/CCL5, interleukin-10 (IL-10), keratinocyte-derived chemokine/CXCL1, IL-12, IL-12p40, and CCL4/macrophage inflammatory protein 1β, were decreased in DZNep-treated mice. Conclusion: EZH2 is up-regulated in multiple cell types in lupus patients. Therapeutic inhibition of EZH2 abrogates lupus-like disease in MRL/lpr mice, suggesting that EZH2 inhibitors may be repurposed as a novel therapeutic option for lupus patients.
MeSH term(s)	Adenosine/analogs & derivatives ; Adenosine/pharmacology ; Adult ; Animals ; Antibodies, Antinuclear/biosynthesis ; Antibodies, Antinuclear/drug effects ; Antibody Formation/drug effects ; B-Lymphocytes/drug effects ; B-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/metabolism ; Cell Proliferation/drug effects ; Cytokines/drug effects ; Cytokines/metabolism ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors ; Enhancer of Zeste Homolog 2 Protein/blood ; Enhancer of Zeste Homolog 2 Protein/genetics ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Female ; Humans ; Kidney/drug effects ; Kidney/pathology ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/metabolism ; Lymph Nodes/drug effects ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred MRL lpr ; Middle Aged ; Monocytes/metabolism ; Neutrophils/metabolism ; Proteinuria ; RNA, Messenger/blood ; RNA, Messenger/metabolism ; Spleen/drug effects ; Survival Rate ; T-Lymphocytes/drug effects
Chemical Substances	Antibodies, Antinuclear ; Cytokines ; RNA, Messenger ; 3-deazaneplanocin (544SH4020S) ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Ezh2 protein, mouse (EC 2.1.1.43) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2019-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.40931
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