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Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19)

Zhao, Chaohui Lisa; Rapkiewicz, Amy; Maghsoodi-Deerwester, Mona; Gupta, Mala; Cao, Wenqing; Palaia, Thomas; Zhou, Jianhong; Ram, Bebu; Vo, Duc; Rafiee, Behnam; Hossein-Zadeh, Zarrin; Dabiri, Bahram; Hanna, Iman
Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.
PMCID:7722493
PMID: 33307078
ISSN: 1532-8392
CID: 4770842

Extracellular vesicles released from human iPSC-derived 3D retinas contain small RNAs with roles in development and differentiation [Meeting Abstract]

Flores-Bellver, M; Zhou, J; Zhong, X; Benito-Martin, A; Mighty, J; Qian, J; Pan, J; Wu, H; Juen, Chen B; Liang, A; Peinado, H; Canto-Soler, M V; Redenti, S
Introduction: Noncoding small RNAs in the retina regulate gene expression by targeting and repressing mRNA. Small RNAs are secreted in extracellular vesicles (EVs). Analysis of EVs released from developing retinal tissue is an essential step in elucidating the role of EV molecular cargo and signalling during retinogenesis. A number of canonical genes are associated with retinal cell fate determination during development, but EV-mediated gene regulation in the retinal microenvironment remains undefined. In this study, we characterize the microRNA, tRNA, and piRNA composition of EVs secreted from human induced pluripotent stem cell (hiPSCs) - derived 3D retinas at three developmental time points that correlate with hallmarks of retinal cell differentiation and lamination in vivo.
Method(s): Retinal organoids were generated from hiPSCs. We selected three developmental time points (day 42, 63 and 90) that represent distinctive stages during normal retinal cell fate specification and lamination. We analysed the release rate, concentration, morphology and content (miRNA, tRNA and pi- RNA) of EVs released from human hiPSCs-derived 3D retinas.
Result(s): The genetic signalling, developmental time course and morphogenesis of these retinal organoids were comparable to those of developing human retinas in vivo. According to Gene Ontology analysis, miRNA targets at the earliest stage of development were more relevant to early differentiation and cell morphogenesis, whereas miRNA targets at the later stages were more relevant to cell proliferation, cell differentiation, and cell migration. Summary/Conclusion: For the first time, this work demonstrates the rate of release and concentration of EVs from developing hiPSC-derived 3D retinal tissue. We report a large variety of small RNAs in EVs from hiPSC-derived 3D retinas, including miRNAs, tRNAs and piRNAs. The full range of small RNAs detected in our EVs may act as regulatory elements to modulate gene activity and may serve as biomarkers of normal development. This work represents the first sequencing analysis of small RNA species contained in hiPSCderived 3D retinas and their released EVs
EMBASE:627699004
ISSN: 2001-3078
CID: 3900182

Erdheim-Chester disease: a rare cause of recurrent fever of unknown origin mimicking lymphoma [Case Report]

Mariampillai, Anusiyanthan; Sivapiragasam, Abirami; Kumar, Amit; Hindenburg, Alexander; Cunha, Burke A; Zhou, Jianhong
We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.
PMID: 24228820
ISSN: 1651-1980
CID: 3433352

Radiology-pathology conference: primary peritoneal mesothelioma [Case Report]

Baadh, Amanjit S; Xiong, Xiaoling; Singh, Sandeep; Kapoor, Rita; Zhou, Jianhong; Katz, Douglas S
Primary peritoneal mesothelioma is a rare neoplasm which carries a dismal prognosis. These highly aggressive tumors arise from mesothelial cells lining the peritoneum and are rapidly fatal. The neoplasm is typically associated with crocidolite asbestos exposure. We present the case of a 75-year-old man with primary peritoneal mesothelioma, with invasion into the right hepatic lobe.
PMID: 23953740
ISSN: 1873-4499
CID: 3002772

A Rare Case of Erdheim-Chester Disease [Meeting Abstract]

Kumar, Amit; Brooks, Michael K.; Mazzie, Joseph; Zhou, Jianhong
ISI:000209468500173
ISSN: 0002-9173
CID: 3275052

The diagnostic value of the ThinPrep pap test in endometrial carcinoma: a prospective study with histological follow-up

Zhou, Jianhong; Tomashefski, Joseph F; Sawady, Joram; Ferrer, Hector; Khiyami, Amer
Case-control studies have demonstrated that the ThinPrep Pap test may provide improved detection of endometrial carcinoma. The purpose of this study is to prospectively examine the diagnostic potential of the ThinPrep Pap test in the detection of endometrial carcinoma. ThinPrep Pap test slides were collected from high-risk patient groups. Pap-stained slides were reviewed and the cytological diagnosis was rendered independently by investigators. Each case was assigned to one of the four diagnostic categories: within normal limit (WNL); atypical glandular cells (AGC); atypical endometrial cells (AEC); or adenocarcinoma, probably endometrial origin. After cytological diagnosis was made, the histological follow-up diagnosis was obtained through the laboratory information system and the cyto-histological correlation was analyzed. Of 106 patients identified, 60 had histological follow-up. For all eight cases interpreted by cytology as positive, endometrial carcinoma was confirmed histologically. Among 25 patients with normal endometrial cells present, histological follow-up showed benign endometrium. Among 17 cases interpreted cytologically as AEC, 14 cases (82.4%) had benign histological follow-up and 3 cases (17.6%) had endometrial carcinoma. All 11 cases (100%) classified as AGC had benign histological follow-up. The sensitivity and specificity of detecting endometrial malignancy were 72.7% and 100%, respectively. The positive predictive value was 100%. In this prospective study, we demonstrated that the Thin Prep Pap test had a reasonably high sensitivity and/or specificity in detecting endometrial carcinoma.
PMID: 22351503
ISSN: 1097-0339
CID: 3499572

Mir-375 enhances ruthenium-derived compound Rawq01 induced cell death in human ovarian cancer

Shao, Xiaowen; Mei, Wenjie; Weng, Wenhao; Qin, Jinlong; Zhou, Jianhong; Liu, Jie; Cheng, Jiajing
UNLABELLED:Ovarian cancer is one of the most common gynecological malignancies. Limited efficacy of cytotoxic chemotherapy is a key obstacle in the treatment of advanced ovarian cancer. This study aimed to investigate whether Mir-375 enhances Rawq01 (a ruthenium derived compound) induced cell death in ovarian cancer. METHODS:Three human ovarian cancer cell lines were selected, and independently treated with Rawq01+mir-375 and Rawq01+control. MTT assay and flow cytometry were performed to detect the growth of ovarian cancer cells. Western blot was carried out to determine the expression of apoptotic associated proteins. In addition, ovarian cancer xenografts were established to explore whether mir-375 increased the in vivo chemosensitivity of ovarian cancer cells to RAWQ01. RESULTS:Over-expression of mir-375 sensitized the ovarian cancer cells to RAWQ01. Mir-375 enhanced the in vitro sensitivity of ovarian cancer cells to RAWQ01 by inducing apoptosis. Mir-375 also increased the in vivo chemosensitivity of ovarian cancer cells to RAWQ01. CONCLUSION/CONCLUSIONS:Mir-375 can enhance Rawq01 induced cell death in human ovarian cancer both in vitro and in vivo.
PMID: 23696927
ISSN: 1936-2625
CID: 3499582

Glycogen-Rich Clear Cell Carcinoma of Breast: A Report of Two Cases With Literature Review [Meeting Abstract]

Tseng, Yun-An; Zhou, Jianhong
ISI:000209848700201
ISSN: 0002-9173
CID: 3499522

Cytologic detection of Strongyloides stercoralis in a 55-year-old Hispanic man with routine rectal/anal pap smear [Case Report]

Zhou, Jianhong; Ferrer, Hector; Cleveland, Ronald; Ganesan, Santhi
The anal-rectal cytology is introduced recently to evaluate human-papillomavirus related cellular changes in the cells of anal canal. It is especially useful in high risk patients such as HIV patients. Very few reports were published regarding cytomorphological findings in anal cytology. Strongyloides stercoralis is an enteric helminthic parasite with particular significance in immunocompromised patients. The infection is asymptomatic or manifests as mild gastrointestinal symptoms in normal hosts. The infection can be devastating in immunocompromised persons, and carries a high mortality rate. The presence of S. stercoralis larva in anal-rectal pap smears is rare. We report a case in a routine anal-rectal Pap smear with Strongyloides, and discuss the clinical significance and life cycle of S. stercoralis.
PMID: 19582805
ISSN: 1097-0339
CID: 3499562

A surface display yeast two-hybrid screening system for high-throughput protein interactome mapping

Chen, Jun; Zhou, Jianhong; Sanders, Claire K; Nolan, John P; Cai, Hong
Despite the wide acceptance of yeast two-hybrid (Y2H) system for protein-protein interaction analysis and discovery, conventional Y2H assays are not well suited for high-throughput screening of the protein interaction network ("interactome") on a genomic scale due to several limitations, including labor-intensive agar plating and colony selection methods associated with the use of nutrient selection markers, complicated reporter analysis methods associated with the use of LacZ enzyme reporters, and incompatibility of the liquid handling robots. We recently reported a robust liquid culture Y2H system based on quantitative analysis of yeast-enhanced green fluorescent protein (yEGFP) reporters that greatly increased the analysis throughput and compatibility with liquid handling robots. To further advance its utility in high-throughput complementary DNA (cDNA) library screening, we report the development of a novel surface display Y2H (sdY2H) library screening system with uniquely integrated surface display hemagglutination (sdHA) antigen and yEGFP reporters. By introduction of a surface reporter sdHA into the yEGFP-based Y2H system, positive Y2H targets are quickly isolated from library cells by a simple magnetic separation without a large plating effort. Moreover, the simultaneous scoring of multiple reporters, including sdHA, yEGFP, and conventional nutrient markers, greatly increased the specificity of the Y2H assay. The feasibility of the sdY2H assay on large cDNA library screening was demonstrated by the successful recovery of positive P53/T interaction pairs at a target-to-background ratio of 1:1,000,000. Together with the massive parallel DNA sequencing technology, it may provide a powerful proteomic tool for high-throughput interactome mapping on a genomic scale.
PMID: 19298787
ISSN: 1096-0309
CID: 3881762