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Article ; Online: MIF modulates p38/ERK phosphorylation via MKP-1 induction in sarcoidosis.

Talreja, Jaya / Peng, Changya / Samavati, Lobelia

iScience

2023 Volume 27, Issue 1, Page(s) 108746

Abstract: Macrophage migration inhibitory factor (MIF) is a versatile cytokine that influences a variety of cellular processes important for immune regulation and tissue homeostasis. Sarcoidosis is a granulomatous disease characterized by extensive local ... ...

Abstract	Macrophage migration inhibitory factor (MIF) is a versatile cytokine that influences a variety of cellular processes important for immune regulation and tissue homeostasis. Sarcoidosis is a granulomatous disease characterized by extensive local inflammation and increased T helper cell mediated cytokines. We have shown that MIF has a modulatory role in cytokine networks in sarcoidosis. We investigated the effect of exogenous MIF on sarcoidosis alveolar macrophages (AMs), CD14
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108746
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Article: Sarcoidosis and neuroendocrine tumours: case report and literature review.

Taha, Muhanad / Samavati, Lobelia

Respirology case reports

2021 Volume 9, Issue 7, Page(s) e00784

Abstract: Rare cases of co-existing sarcoidosis and carcinoid tumour have been previously reported in the literature. Both diseases may have vague and overlapping clinical presentations that can lead to delayed or missed diagnosis. To avoid this diagnostic pitfall, ...

Abstract	Rare cases of co-existing sarcoidosis and carcinoid tumour have been previously reported in the literature. Both diseases may have vague and overlapping clinical presentations that can lead to delayed or missed diagnosis. To avoid this diagnostic pitfall, we discuss and compare the clinical presentations of all reported cases in the literature including our case. We also provide hypothesis to explain the relationship between the two diseases.
Language	English
Publishing date	2021-05-27
Publishing country	United States
Document type	Case Reports
ZDB-ID	2750180-2
ISSN	2051-3380
ISSN	2051-3380
DOI	10.1002/rcr2.784
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Article ; Online: Discovery of Two Novel Immunoepitopes and Development of Peptide-based Sarcoidosis Immunoassay.

Peng, Changya / Talreja, Jaya / Steinbauer, Brennen / Shinki, Kazuhiko / Koth, Laura L / Samavati, Lobelia

American journal of respiratory and critical care medicine

2024

Abstract: Rationale: Sarcoidosis is a systemic granulomatous disorder associated with hypergammaglobulinemia and the presence of autoantibodies. The specific antigens initiating granulomatous inflammation in sarcoidosis are unknown and there is no specific test ... ...

Abstract	Rationale: Sarcoidosis is a systemic granulomatous disorder associated with hypergammaglobulinemia and the presence of autoantibodies. The specific antigens initiating granulomatous inflammation in sarcoidosis are unknown and there is no specific test available to diagnose sarcoidosis. To discover novel sarcoidosis antigens, we developed a high-throughput T7 phage display library derived from the sarcoidosis cDNA and identified numerous clones differentiating sarcoidosis from other respiratory diseases. After clone sequencing and homology search, we identified two epitopes (Cofilinμ and Chain A) that specifically bind to serum IgGs of sarcoidosis patients. Objectives: To develop and validate an epitope-specific IgG-based immunoassay specific for sarcoidosis. Methods: We chemically synthesized both immunoepitopes (Cofilinμ and Chain A), and generated rabbit polyclonal antibodies against both neoantigens. After extensive standardization, we developed a direct peptide ELISA and measured epitope-specific IgG in sera of 386 subjects including, healthy controls (n=100), three sarcoidosis cohorts (n=186), pulmonary tuberculosis (n=70) and lung cancer (n=30). Measurements and main results: To develop a model to classify sarcoidosis from other groups, data were analyzed using five-fold cross-validation when adjusting for confounders. The Cofilinμ IgGs model yielded a mean sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of 0.97, 0.9, 0.9 and 0.96, respectively. Those same measures for Chain A IgG antibody were 0.9, 0.83, 0.84 and 0.9 respectively. Combining both biomarkers improved AUC, sensitivity, specificity, PPV and NPV. Conclusions: These results provide a novel immunoassay for sarcoidosis. The discovery of two neoantigens facilitates the development of biospecific drug discovery and the sarcoidosis-specific model.
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202306-1054OC
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Article ; Online: Antiphospholipid antibodies in COVID-19: a meta-analysis and systematic review.

Taha, Muhanad / Samavati, Lobelia

RMD open

2021 Volume 7, Issue 2

Abstract: Background: Many studies reported high prevalence of antiphospholipid antibodies (aPL) in patients with COVID-19 raising questions about its true prevalence and its clinical impact on the disease course.: Methods: We conducted a meta-analysis and a ... ...

Abstract	Background: Many studies reported high prevalence of antiphospholipid antibodies (aPL) in patients with COVID-19 raising questions about its true prevalence and its clinical impact on the disease course. Methods: We conducted a meta-analysis and a systematic review to examine the prevalence of aPL and its clinical impact in patients with COVID-19. Results: 21 studies with a total of 1159 patients were included in our meta-analysis. Among patients hospitalised with COVID-19, the pooled prevalence rate of one or more aPL (IgM or IgG or IgA of anticardiolipin (aCL) or anti-ß2 glycoprotein (anti-ß2 GPI) or antiphosphatidylserine/prothrombin, or lupus anticoagulant (LA)) was 46.8% (95% CI 36.1% to 57.8%). The most frequent type of aPL found was LA, with pooled prevalence rate of 50.7% (95% CI 34.8% to 66.5%). Critically ill patients with COVID-19 had significantly higher prevalence of aCL (IgM or IgG) (28.8% vs 7.10%, p<0.0001) and anti-ß2 GPI (IgM or IgG) (12.0% vs 5.8%, p<0.0001) as compared with non-critically ill patients. However, there was no association between aPL positivity and mean levels of C reactive protein (mean difference was 32 (95% CI -15 to 79), p=0.18), D-dimer (mean difference was 34 (95% CI -194 to 273), p=0.77), mortality (1.46 (95% CI 0.29 to 7.29), p=0.65), invasive ventilation (1.22 (95% CI 0.51 to 2.91), p=0.65) and venous thromboembolism (1.38 (95% CI 0.57 to 3.37), p=0.48). Conclusions: aPLs were detected in nearly half of patients with COVID-19, and higher prevalence of aPL was found in severe disease. However, there was no association between aPL positivity and disease outcomes including thrombosis, invasive ventilation and mortality. However, further studies are required to identify the clinical and pathological role of aPL in COVID-19.
MeSH term(s)	Antibodies, Antiphospholipid/blood ; Antibodies, Antiphospholipid/classification ; Biomarkers/blood ; COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/immunology ; Critical Illness ; Humans ; Prevalence ; SARS-CoV-2 ; Severity of Illness Index
Chemical Substances	Antibodies, Antiphospholipid ; Biomarkers
Language	English
Publishing date	2021-05-06
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Systematic Review
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2021-001580
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Article ; Online: Antiphospholipid antibodies in COVID-19

Muhanad Taha / Lobelia Samavati

RMD Open, Vol 7, Iss

a meta-analysis and systematic review

2021 Volume 2

Abstract: Background Many studies reported high prevalence of antiphospholipid antibodies (aPL) in patients with COVID-19 raising questions about its true prevalence and its clinical impact on the disease course.Methods We conducted a meta-analysis and a ... ...

Abstract	Background Many studies reported high prevalence of antiphospholipid antibodies (aPL) in patients with COVID-19 raising questions about its true prevalence and its clinical impact on the disease course.Methods We conducted a meta-analysis and a systematic review to examine the prevalence of aPL and its clinical impact in patients with COVID-19.Results 21 studies with a total of 1159 patients were included in our meta-analysis. Among patients hospitalised with COVID-19, the pooled prevalence rate of one or more aPL (IgM or IgG or IgA of anticardiolipin (aCL) or anti-ß2 glycoprotein (anti-ß2 GPI) or antiphosphatidylserine/prothrombin, or lupus anticoagulant (LA)) was 46.8% (95% CI 36.1% to 57.8%). The most frequent type of aPL found was LA, with pooled prevalence rate of 50.7% (95% CI 34.8% to 66.5%). Critically ill patients with COVID-19 had significantly higher prevalence of aCL (IgM or IgG) (28.8% vs 7.10%, p<0.0001) and anti-ß2 GPI (IgM or IgG) (12.0% vs 5.8%, p<0.0001) as compared with non-critically ill patients. However, there was no association between aPL positivity and mean levels of C reactive protein (mean difference was 32 (95% CI −15 to 79), p=0.18), D-dimer (mean difference was 34 (95% CI −194 to 273), p=0.77), mortality (1.46 (95% CI 0.29 to 7.29), p=0.65), invasive ventilation (1.22 (95% CI 0.51 to 2.91), p=0.65) and venous thromboembolism (1.38 (95% CI 0.57 to 3.37), p=0.48).Conclusions aPLs were detected in nearly half of patients with COVID-19, and higher prevalence of aPL was found in severe disease. However, there was no association between aPL positivity and disease outcomes including thrombosis, invasive ventilation and mortality. However, further studies are required to identify the clinical and pathological role of aPL in COVID-19.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Incidence and risk factors of COVID-19 associated pneumothorax.

Taha, Muhanad / Elahi, Morvarid / Wahby, Krista / Samavati, Lobelia

PloS one

2022 Volume 17, Issue 8, Page(s) e0271964

Abstract: Background: Pneumothorax has been increasingly observed among patients with coronavirus disease-2019 (COVID-19) pneumonia, specifically in those patients who develop acute respiratory distress syndrome (ARDS). In this study, we sought to determine the ... ...

Abstract	Background: Pneumothorax has been increasingly observed among patients with coronavirus disease-2019 (COVID-19) pneumonia, specifically in those patients who develop acute respiratory distress syndrome (ARDS). In this study, we sought to determine the incidence and potential risk factors of pneumothorax in critically ill adults with COVID-19. Method: This retrospective cohort study included adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to one of the adult intensive care units of a tertiary, academic teaching hospital from May 2020 through May 2021. Results: Among 334 COVID-19 cases requiring ICU admission, the incidence of pneumothorax was 10% (33 patients). Patients who experienced pneumothorax more frequently required vasopressor support (28/33 [84%] vs. 191/301 [63%] P = 0.04), were more likely to be proned (25/33 [75%] vs. 111/301 [36%], P<0.001), and the presence of pneumothorax was associated with prolonged duration of mechanical ventilation; 21 (1-97) versus 7 (1-79) days, p<0.001 as well as prolonged hospital length of stay (29 [9-133] vs. 15 [1-90] days, P<0.001), but mortality was not significantly different between groups. Importantly, when we performed a Cox proportional hazard ratio (HR) model of multivariate parameters, we found that administration of tocilizumab significantly increased the risk of developing pneumothorax (HR = 10.7; CI [3.6-32], P<0.001). Conclusion: Among 334 critically ill patients with COVID-19, the incidence of pneumothorax was 10%. Presence of pneumothorax was associated with prolonged duration of mechanical ventilation and length of hospital stay. Strikingly, receipt of tocilizumab was associated with an increased risk of developing pneumothorax.
MeSH term(s)	Adult ; COVID-19/complications ; Critical Illness ; Humans ; Incidence ; Intensive Care Units ; Pneumothorax/epidemiology ; Pneumothorax/etiology ; Respiration, Artificial ; Retrospective Studies ; Risk Factors ; SARS-CoV-2
Language	English
Publishing date	2022-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0271964
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Article ; Online: Incidence and risk factors of COVID-19 associated pneumothorax.

Muhanad Taha / Morvarid Elahi / Krista Wahby / Lobelia Samavati

PLoS ONE, Vol 17, Iss 8, p e

2022 Volume 0271964

Abstract: Background Pneumothorax has been increasingly observed among patients with coronavirus disease-2019 (COVID-19) pneumonia, specifically in those patients who develop acute respiratory distress syndrome (ARDS). In this study, we sought to determine the ... ...

Abstract	Background Pneumothorax has been increasingly observed among patients with coronavirus disease-2019 (COVID-19) pneumonia, specifically in those patients who develop acute respiratory distress syndrome (ARDS). In this study, we sought to determine the incidence and potential risk factors of pneumothorax in critically ill adults with COVID-19. Method This retrospective cohort study included adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to one of the adult intensive care units of a tertiary, academic teaching hospital from May 2020 through May 2021. Results Among 334 COVID-19 cases requiring ICU admission, the incidence of pneumothorax was 10% (33 patients). Patients who experienced pneumothorax more frequently required vasopressor support (28/33 [84%] vs. 191/301 [63%] P = 0.04), were more likely to be proned (25/33 [75%] vs. 111/301 [36%], P<0.001), and the presence of pneumothorax was associated with prolonged duration of mechanical ventilation; 21 (1-97) versus 7 (1-79) days, p<0.001 as well as prolonged hospital length of stay (29 [9-133] vs. 15 [1-90] days, P<0.001), but mortality was not significantly different between groups. Importantly, when we performed a Cox proportional hazard ratio (HR) model of multivariate parameters, we found that administration of tocilizumab significantly increased the risk of developing pneumothorax (HR = 10.7; CI [3.6-32], P<0.001). Conclusion Among 334 critically ill patients with COVID-19, the incidence of pneumothorax was 10%. Presence of pneumothorax was associated with prolonged duration of mechanical ventilation and length of hospital stay. Strikingly, receipt of tocilizumab was associated with an increased risk of developing pneumothorax.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Discovery of Novel Transketolase Epitopes and the Development of IgG-Based Tuberculosis Serodiagnostics.

Talreja, Jaya / Peng, Changya / Nguyen, Tuan-Minh / Draghici, Sorin / Samavati, Lobelia

Microbiology spectrum

2023 Volume 11, Issue 1, Page(s) e0337722

Abstract: Despite advances in rapid molecular techniques for tuberculosis (TB) diagnostics, there is an unmet need for a point-of-care, nonsputum-based test. Previously, through a T7 phage antigen display platform and immunoscreening, we identified that the serum ... ...

Abstract	Despite advances in rapid molecular techniques for tuberculosis (TB) diagnostics, there is an unmet need for a point-of-care, nonsputum-based test. Previously, through a T7 phage antigen display platform and immunoscreening, we identified that the serum IgGs of active TB patients differentially bind to several antigen-clones and that this immunoreactivity discriminates TB from other respiratory diseases. One of these high-performance clones has some homology to the transketolase of Mycobacterium tuberculosis (
MeSH term(s)	Humans ; Transketolase ; Epitopes ; Tuberculosis ; Mycobacterium tuberculosis ; Latent Tuberculosis/diagnosis ; Antigens, Bacterial ; Immunoglobulin G ; Sarcoidosis
Chemical Substances	Transketolase (EC 2.2.1.1) ; Epitopes ; Antigens, Bacterial ; Immunoglobulin G
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.03377-22
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Article ; Online: ACE2, Much More Than Just a Receptor for SARS-COV-2.

Samavati, Lobelia / Uhal, Bruce D

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 317

Abstract: The rapidly evolving pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection worldwide cost many lives. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. As such, it ... ...

Abstract	The rapidly evolving pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection worldwide cost many lives. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. As such, it is now receiving renewed attention as a potential target for anti-viral therapeutics. We review the physiological functions of ACE2 in the cardiovascular system and the lungs, and how the activation of ACE2/MAS/G protein coupled receptor contributes in reducing acute injury and inhibiting fibrogenesis of the lungs and protecting the cardiovascular system. In this perspective, we predominantly focus on the impact of SARS-CoV-2 infection on ACE2 and dysregulation of the protective effect of ACE2/MAS/G protein pathway vs. the deleterious effect of Renin/Angiotensin/Aldosterone. We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host. Furthermore, we speculate the potential of exploiting the modulation of ACE2/MAS pathway as a natural protection of lung injury by modulation of ACE2/MAS axis or by developing targeted drugs to inhibit proteases required for viral entry.
MeSH term(s)	Alveolar Epithelial Cells/metabolism ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus/metabolism ; COVID-19 ; Coronavirus Infections/pathology ; Host-Pathogen Interactions/physiology ; Humans ; Lung/pathology ; Lung/virology ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/pathology ; Receptors, Virus/metabolism ; Renin-Angiotensin System/physiology ; SARS-CoV-2 ; Virus Internalization
Chemical Substances	Receptors, Virus ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-06-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.00317
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Article ; Online: ACE2, Much More Than Just a Receptor for SARS-COV-2

Lobelia Samavati / Bruce D. Uhal

Frontiers in Cellular and Infection Microbiology, Vol

2020 Volume 10

Abstract	The rapidly evolving pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection worldwide cost many lives. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. As such, it is now receiving renewed attention as a potential target for anti-viral therapeutics. We review the physiological functions of ACE2 in the cardiovascular system and the lungs, and how the activation of ACE2/MAS/G protein coupled receptor contributes in reducing acute injury and inhibiting fibrogenesis of the lungs and protecting the cardiovascular system. In this perspective, we predominantly focus on the impact of SARS-CoV-2 infection on ACE2 and dysregulation of the protective effect of ACE2/MAS/G protein pathway vs. the deleterious effect of Renin/Angiotensin/Aldosterone. We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host. Furthermore, we speculate the potential of exploiting the modulation of ACE2/MAS pathway as a natural protection of lung injury by modulation of ACE2/MAS axis or by developing targeted drugs to inhibit proteases required for viral entry.
Keywords	COVID-19 ; lung ; alveolar ; angiotensin ; coagulopathy ; Microbiology ; QR1-502 ; covid19
Subject code	570
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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