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  1. Article ; Online: Characterization of antibodies to SARS-CoV-2 in lyophilized plasma prepared with amotosalen-UVA pathogen reduction.

    Martinaud, Christophe / Bagri, Anil / Tsai, Cheng-Ting / de Assis, Rafael R / Gatmaitan, Michelle / Robinson, Peter V / Seftel, David / Khan, Saahir / Felgner, Philip L / Corash, Laurence M

    Transfusion

    2023  Volume 63, Issue 9, Page(s) 1633–1638

    Abstract: Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients exhibit disease ranging from asymptomatic to severe pneumonia, multi-organ failure, and death. convalescent COVID plasma (CCP) from recovered patients with high ... ...

    Abstract Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients exhibit disease ranging from asymptomatic to severe pneumonia, multi-organ failure, and death. convalescent COVID plasma (CCP) from recovered patients with high levels of neutralizing antibodies has demonstrated therapeutic efficacy to reduce the morbidity of coronavirus disease 2019 (COVID-19) in some studies. The development of assays to characterize the activity of CCP to neutralize SARS-CoV-2 infectivity offers the possibility to improve potential therapeutic efficacy. Lyophilization of CCP may increase the availability of this therapy. We hypothesized that SARS-CoV-2 antibody profiles of pooled lyophilized pathogen-reduced CCP from COVID-19-recovered blood donors retains virus-neutralizing efficacy as reported for frozen pathogen-reduced CCP.
    Methods: Pooled lyophilized pathogen-reduced plasma was prepared from recovered COVID plasma donors. Antibodies to SARS-CoV-2 were characterized in each donor plasma prior to pathogen reduction and lyophilization and after lyophilization of individual CCP, and in the lyophilized CCP pool. Several complimentary assays were used to characterize antibody levels, neutralizing capacity, and the spectrum of antigen reactivity. The mean values for individual plasma samples and the value in the pool were compared.
    Results: The mean ratio for antibody binding to SARS-CoV-2 antigens before and after treatment was 0.95 ± 0.22 mean fluorescent intensity (MFI) units. Antibody activity to an array of influenza virus antigens demonstrated a mean activity ratio of 0.92 ± 0.12 MFI before and after treatment.
    Conclusions: The antibody activity in pooled pathogen-reduced lyophilized CCPs demonstrated minimal impact due to pathogen reduction treatment and lyophilization.
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19/therapy ; Furocoumarins ; Antibodies, Neutralizing
    Chemical Substances amotosalen (K1LDZ0VBC0) ; Furocoumarins ; Antibodies, Neutralizing
    Language English
    Publishing date 2023-08-24
    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.17506
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  2. Article ; Online: Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma.

    Barry, Mark / Trivedi, Alpa / Miyazawa, Byron Y / Vivona, Lindsay R / Khakoo, Manisha / Zhang, Haoqian / Pathipati, Praneeti / Bagri, Anil / Gatmaitan, Michelle G / Kozar, Rosemary / Stein, Deborah / Pati, Shibani

    The journal of trauma and acute care surgery

    2020  Volume 90, Issue 6, Page(s) 1022–1031

    Abstract: Background: Plasma has been shown to mitigate the endotheliopathy of trauma. Protection of the endothelium may be due in part to fibrinogen and other plasma-derived proteins found in cryoprecipitate; however, the exact mechanisms remain unknown. ... ...

    Abstract Background: Plasma has been shown to mitigate the endotheliopathy of trauma. Protection of the endothelium may be due in part to fibrinogen and other plasma-derived proteins found in cryoprecipitate; however, the exact mechanisms remain unknown. Clinical trials are underway investigating early cryoprecipitate administration in trauma. In this study, we hypothesize that cryoprecipitate will inhibit endothelial cell (EC) permeability in vitro and will replicate the ability of plasma to attenuate pulmonary vascular permeability and inflammation induced by hemorrhagic shock and trauma (HS/T) in mice.
    Methods: In vitro, barrier permeability of ECs subjected to thrombin challenge was measured by transendothelial electrical resistance. In vivo, using an established mouse model of HS/T, we compared pulmonary vascular permeability among mice resuscitated with (1) lactated Ringer's solution (LR), (2) fresh frozen plasma (FFP), or (3) cryoprecipitate. Lung tissue from the mice in all groups was analyzed for markers of vascular integrity, inflammation, and inflammatory gene expression via NanoString messenger RNA quantification.
    Results: Cryoprecipitate attenuates EC permeability and EC junctional compromise induced by thrombin in vitro in a dose-dependent fashion. In vivo, resuscitation of HS/T mice with either FFP or cryoprecipitate attenuates pulmonary vascular permeability (sham, 297 ± 155; LR, 848 ± 331; FFP, 379 ± 275; cryoprecipitate, 405 ± 207; p < 0.01, sham vs. LR; p < 0.01, LR vs. FFP; and p < 0.05, LR vs. cryoprecipitate). Lungs from cryoprecipitate- and FFP-treated mice demonstrate decreased lung injury, decreased infiltration of neutrophils and activation of macrophages, and preserved pericyte-endothelial interaction compared with LR-treated mice. Gene analysis of lung tissue from cryoprecipitate- and FFP-treated mice demonstrates decreased inflammatory gene expression, in particular, IL-1β and NLRP3, compared with LR-treated mice.
    Conclusion: Our data suggest that cryoprecipitate attenuates the endotheliopathy of trauma in HS/T similar to FFP. Further investigation is warranted on active components and their mechanisms of action.
    MeSH term(s) Animals ; Capillary Permeability ; Disease Models, Animal ; Endothelium, Vascular/cytology ; Endothelium, Vascular/pathology ; Human Umbilical Vein Endothelial Cells ; Humans ; Lung/cytology ; Lung/pathology ; Lung Injury/etiology ; Lung Injury/pathology ; Lung Injury/therapy ; Male ; Mice ; Plasma ; Ringer's Lactate/administration & dosage ; Shock, Hemorrhagic/etiology ; Shock, Hemorrhagic/pathology ; Shock, Hemorrhagic/therapy ; Wounds and Injuries/complications ; Wounds and Injuries/therapy
    Chemical Substances Ringer's Lactate
    Language English
    Publishing date 2020-12-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2651070-4
    ISSN 2163-0763 ; 2163-0755
    ISSN (online) 2163-0763
    ISSN 2163-0755
    DOI 10.1097/TA.0000000000003164
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 127: Show issues Location:
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  3. Article ; Online: Antibody profiles in COVID-19 convalescent plasma prepared with amotosalen/UVA pathogen reduction treatment.

    Bagri, Anil / de Assis, Rafael R / Tsai, Cheng-Ting / Simmons, Graham / Mei, Zhen W / Von Goetz, Melissa / Gatmaitan, Michelle / Stone, Mars / Di Germanio, Clara / Martinelli, Rachel / Darst, Orsolya / Rioveros, Jowin / Robinson, Peter V / Ward, Dawn / Ziman, Alyssa / Seftel, David / Khan, Saahir / Busch, Michael P / Felgner, Philip L /
    Corash, Laurence M

    Transfusion

    2022  Volume 62, Issue 3, Page(s) 570–583

    Abstract: Background: COVID-19 convalescent plasma (CCP), from donors recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the limited therapeutic options currently available for the treatment of critically ill patients ...

    Abstract Background: COVID-19 convalescent plasma (CCP), from donors recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the limited therapeutic options currently available for the treatment of critically ill patients with COVID-19. There is growing evidence that CCP may reduce viral loads and disease severity; and reduce mortality. However, concerns about the risk of transfusion-transmitted infections (TTI) and other complications associated with transfusion of plasma, remain. Amotosalen/UVA pathogen reduction treatment (A/UVA-PRT) of plasma offers a mitigation of TTI risk, and when combined with pooling has the potential to increase the diversity of the polyclonal SARS-CoV-2 neutralizing antibodies.
    Study design and methods: This study assessed the impact of A/UVA-PRT on SARS-CoV-2 antibodies in 42 CCP using multiple complimentary assays including antigen binding, neutralizing, and epitope microarrays. Other mediators of CCP efficacy were also assessed.
    Results: A/UVA-PRT did not negatively impact antibodies to SARS-CoV-2 and other viral epitopes, had no impact on neutralizing activity or other potential mediators of CCP efficacy. Finally, immune cross-reactivity with other coronavirus antigens was observed raising the potential for neutralizing activity against other emergent coronaviruses.
    Conclusion: The findings of this study support the selection of effective CCP combined with the use of A/UVA-PRT in the production of CCP for patients with COVID-19.
    MeSH term(s) Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/therapy ; Furocoumarins ; Humans ; Immunization, Passive ; SARS-CoV-2
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Furocoumarins ; amotosalen (K1LDZ0VBC0)
    Language English
    Publishing date 2022-02-12
    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.16819
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    Zs.A 284: Show issues Location:
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  4. Article ; Online: Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

    Decaris, Martin L / Li, Kelvin W / Emson, Claire L / Gatmaitan, Michelle / Liu, Shanshan / Wang, Yenny / Nyangau, Edna / Colangelo, Marc / Angel, Thomas E / Beysen, Carine / Cui, Jeffrey / Hernandez, Carolyn / Lazaro, Len / Brenner, David A / Turner, Scott M / Hellerstein, Marc K / Loomba, Rohit

    Hepatology (Baltimore, Md.)

    2017  Volume 65, Issue 1, Page(s) 78–88

    Abstract: Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to ... ...

    Abstract Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water (
    Conclusion: Using a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88).
    MeSH term(s) Biopsy ; Collagen/metabolism ; Disease Progression ; Extracellular Matrix/metabolism ; Female ; Humans ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/blood ; Liver Cirrhosis/complications ; Liver Cirrhosis/pathology ; Lumican/blood ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/complications
    Chemical Substances Lumican ; Collagen (9007-34-5)
    Language English
    Publishing date 2017-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.28860
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    Zs.A 1660: Show issues Location:
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  5. Article ; Online: Turnover rates of hepatic collagen and circulating collagen-associated proteins in humans with chronic liver disease.

    Decaris, Martin L / Emson, Claire L / Li, Kelvin / Gatmaitan, Michelle / Luo, Flora / Cattin, Jerome / Nakamura, Corelle / Holmes, William E / Angel, Thomas E / Peters, Marion G / Turner, Scott M / Hellerstein, Marc K

    PloS one

    2015  Volume 10, Issue 4, Page(s) e0123311

    Abstract: Accumulation and degradation of scar tissue in fibrotic liver disease occur slowly, typically over many years. Direct measurement of fibrogenesis, the rate of scar tissue deposition, may provide valuable therapeutic and prognostic information. We ... ...

    Abstract Accumulation and degradation of scar tissue in fibrotic liver disease occur slowly, typically over many years. Direct measurement of fibrogenesis, the rate of scar tissue deposition, may provide valuable therapeutic and prognostic information. We describe here results from a pilot study utilizing in vivo metabolic labeling to measure the turnover rate of hepatic collagen and collagen-associated proteins in plasma for the first time in human subjects. Eight subjects with chronic liver disease were labeled with daily oral doses of 2H2O for up to 8 weeks prior to diagnostic liver biopsy and plasma collection. Tandem mass spectrometry was used to measure the abundance and fractional synthesis rate (FSR) of proteins in liver and blood. Relative protein abundance and FSR data in liver revealed marked differences among subjects. FSRs of hepatic type I and III collagen ranged from 0.2-0.6% per day (half-lives of 4 months to a year) and correlated significantly with worsening histologic fibrosis. Analysis of plasma protein turnover revealed two collagen-associated proteins, lumican and transforming growth factor beta-induced-protein (TGFBI), exhibiting FSRs that correlated significantly with FSRs of hepatic collagen. In summary, this is the first direct measurement of liver collagen turnover in vivo in humans and suggests a high rate of collagen remodeling in advanced fibrosis. In addition, the FSRs of collagen-associated proteins in plasma are measurable and may provide a novel strategy for monitoring hepatic fibrogenesis rates.
    MeSH term(s) Adult ; Aged ; Biopsy ; Carrier Proteins/blood ; Cluster Analysis ; Collagen/metabolism ; Female ; Humans ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/blood ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Liver Diseases/blood ; Liver Diseases/diagnosis ; Liver Diseases/etiology ; Liver Diseases/metabolism ; Liver Diseases/pathology ; Male ; Middle Aged ; Pilot Projects ; Protein Binding ; Proteome ; Proteomics/methods ; Transforming Growth Factor beta1/metabolism
    Chemical Substances Carrier Proteins ; Proteome ; Transforming Growth Factor beta1 ; Collagen (9007-34-5)
    Language English
    Publishing date 2015-04-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0123311
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  6. Article ; Online: Proteomic analysis of altered extracellular matrix turnover in bleomycin-induced pulmonary fibrosis.

    Decaris, Martin L / Gatmaitan, Michelle / FlorCruz, Simplicia / Luo, Flora / Li, Kelvin / Holmes, William E / Hellerstein, Marc K / Turner, Scott M / Emson, Claire L

    Molecular & cellular proteomics : MCP

    2014  Volume 13, Issue 7, Page(s) 1741–1752

    Abstract: Fibrotic disease is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Surprisingly, very little is known about the synthesis and degradation rates of the many proteins and proteoglycans that constitute healthy or ... ...

    Abstract Fibrotic disease is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Surprisingly, very little is known about the synthesis and degradation rates of the many proteins and proteoglycans that constitute healthy or pathological extracellular matrix. A comprehensive understanding of altered ECM protein synthesis and degradation during the onset and progression of fibrotic disease would be immensely valuable. We have developed a dynamic proteomics platform that quantifies the fractional synthesis rates of large numbers of proteins via stable isotope labeling and LC/MS-based mass isotopomer analysis. Here, we present the first broad analysis of ECM protein kinetics during the onset of experimental pulmonary fibrosis. Mice were labeled with heavy water for up to 21 days following the induction of lung fibrosis with bleomycin. Lung tissue was subjected to sequential protein extraction to fractionate cellular, guanidine-soluble ECM proteins and residual insoluble ECM proteins. Fractional synthesis rates were calculated for 34 ECM proteins or protein subunits, including collagens, proteoglycans, and microfibrillar proteins. Overall, fractional synthesis rates of guanidine-soluble ECM proteins were faster than those of insoluble ECM proteins, suggesting that the insoluble fraction reflected older, more mature matrix components. This was confirmed through the quantitation of pyridinoline cross-links in each protein fraction. In fibrotic lung tissue, there was a significant increase in the fractional synthesis of unique sets of matrix proteins during early (pre-1 week) and late (post-1 week) fibrotic response. Furthermore, we isolated fast turnover subpopulations of several ECM proteins (e.g. type I collagen) based on guanidine solubility, allowing for accelerated detection of increased synthesis of typically slow-turnover protein populations. This establishes the presence of multiple kinetic pools of pulmonary collagen in vivo with altered turnover rates during evolving fibrosis. These data demonstrate the utility of dynamic proteomics in analyzing changes in ECM protein turnover associated with the onset and progression of fibrotic disease.
    MeSH term(s) Animals ; Basement Membrane/metabolism ; Bleomycin/pharmacology ; Collagen Type I/biosynthesis ; Collagen Type I/metabolism ; Deuterium Oxide ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Extracellular Matrix Proteins/metabolism ; Gas Chromatography-Mass Spectrometry ; Gene Expression Profiling ; Isotope Labeling ; Mice ; Mice, Inbred C57BL ; Microfibrils/metabolism ; Proteoglycans/metabolism ; Proteomics ; Pulmonary Fibrosis/chemically induced ; Pulmonary Fibrosis/pathology
    Chemical Substances Collagen Type I ; Extracellular Matrix Proteins ; Proteoglycans ; Bleomycin (11056-06-7) ; Deuterium Oxide (J65BV539M3)
    Language English
    Publishing date 2014-04-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2075924-1
    ISSN 1535-9484 ; 1535-9476
    ISSN (online) 1535-9484
    ISSN 1535-9476
    DOI 10.1074/mcp.M113.037267
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    Zs.A 5599: Show issues Location:
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  7. Article ; Online: Direct in vivo evidence for increased proliferation of CLL cells in lymph nodes compared to bone marrow and peripheral blood.

    Herndon, Thomas M / Chen, Shih-Shih / Saba, Nakhle S / Valdez, Janet / Emson, Claire / Gatmaitan, Michelle / Tian, Xin / Hughes, Thomas E / Sun, Clare / Arthur, Diane C / Stetler-Stevenson, Maryalice / Yuan, Constance M / Niemann, Carsten U / Marti, Gerald E / Aue, Georg / Soto, Susan / Farooqui, Mohammed Z H / Herman, Sarah E M / Chiorazzi, Nicholas /
    Wiestner, Adrian

    Leukemia

    2017  Volume 31, Issue 6, Page(s) 1340–1347

    Abstract: Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells are in a resting state, small populations of ... ...

    Abstract Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells are in a resting state, small populations of proliferating cells exist; however, the anatomical site of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of 'newly born' cells would be highest in the LNs. Using a deuterium oxide (
    MeSH term(s) Aged ; Apoptosis ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; B-Lymphocytes/pathology ; Bone Marrow/immunology ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Cell Proliferation ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/pathology ; Lymph Nodes/immunology ; Lymph Nodes/metabolism ; Lymph Nodes/pathology ; Lymphocyte Activation ; Male ; Middle Aged ; Tumor Cells, Cultured
    Language English
    Publishing date 2017-01-11
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/leu.2017.11
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