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Book ; Online ; Thesis: Pathogenese der HIV-Infektion bei Kindern

2022

Author's details	Maximilian Muenchhoff
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Universitätsbibliothek der Ludwig-Maximilians-Universität
Publishing place	München
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Barriere auf dem Weg zur Heilung.

Muenchhoff, Maximilian / Keppler, Oliver T

MMW Fortschritte der Medizin

2018 Volume 160, Issue Suppl 2, Page(s) 32–35

Title translation	The HIV reservoir in resting CD4 T-cells: Barrier on the road to an HIV cure.
MeSH term(s)	Anti-HIV Agents/therapeutic use ; CD4-Positive T-Lymphocytes/immunology ; Disease Reservoirs ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Virus Latency
Chemical Substances	Anti-HIV Agents
Language	German
Publishing date	2018-06-22
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1478211-x
ISSN	1613-3560 ; 1438-3276
ISSN (online)	1613-3560
ISSN	1438-3276
DOI	10.1007/s15006-018-0653-3
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Article ; Online: Magnitude of Type I Interferon Responses by Plasmacytoid Dendritic Cells After TLR7 Stimulation Is Associated With Human Immunodeficiency Virus Type 1 (HIV-1) Reservoir Sizes in Cisgender Women With HIV-1 on Antiretroviral Therapy.

Thiele, Rebecca-Jo / Grünhagel, Benjamin / Muenchhoff, Maximilian / Pujantell-Graell, Maria / Jocham, Linda / Düsedau, Arne / Hennesen, Jana / Hildebrandt, Heike / Hagen, Sven Hendrik / Sandfort, Deborah / Bunders, Madeleine J / Keppler, Oliver T / Hoffmann, Christian / Altfeld, Marcus

The Journal of infectious diseases

2024

Abstract: Human immunodeficiency virus type 1 (HIV-1) disease manifestations differ between cisgender women and men, including better control of viral replication during primary infection and less frequent residual HIV-1 replication on antiretroviral therapy (ART) ...

Abstract	Human immunodeficiency virus type 1 (HIV-1) disease manifestations differ between cisgender women and men, including better control of viral replication during primary infection and less frequent residual HIV-1 replication on antiretroviral therapy (ART) in cisgender women with HIV-1 (WWH). Investigating plasmacytoid dendritic cell (pDC) functions and HIV-1 reservoir sizes in 20 WWH on stable ART, we observed inverse correlations between interferon-α and tumor necrosis factor responses of pDCs to Toll-like receptor 7/8 stimulation and intact/total proviral HIV-1 DNA levels. Additionally, ISG15 mRNA levels in peripheral blood mononuclear cells correlated with cytokine responses of pDCs. These findings demonstrate an association between higher type I interferon responses and lower HIV-1 reservoir sizes in WWH on ART, warranting studies to identify the underlying mechanisms.
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae013
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Article: Ketone Bodies Improve Human CD8

Hirschberger, Simon / Gellert, Luca / Effinger, David / Muenchhoff, Maximilian / Herrmann, Markus / Briegel, Josef-Maria / Zwißler, Bernhard / Kreth, Simone

Frontiers in medicine

2022 Volume 9, Page(s) 923502

Abstract: Severe COVID-19 is characterized by profound ... ...

Abstract	Severe COVID-19 is characterized by profound CD8
Language	English
Publishing date	2022-06-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.923502
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Article ; Online: Liver function test abnormalities at hospital admission are associated with severe course of SARS-CoV-2 infection: a prospective cohort study.

Weber, Sabine / Hellmuth, Johannes C / Scherer, Clemens / Muenchhoff, Maximilian / Mayerle, Julia / Gerbes, Alexander L

Gut

2021 Volume 70, Issue 10, Page(s) 1925–1932

Abstract: Objective: Liver injury has frequently been reported in COVID-19 patients. The clinical relevance of liver injury related to SARS-CoV-2 infection remains unclear with a need for prospective studies on the impact of liver function test (LFT) ... ...

Abstract	Objective: Liver injury has frequently been reported in COVID-19 patients. The clinical relevance of liver injury related to SARS-CoV-2 infection remains unclear with a need for prospective studies on the impact of liver function test (LFT) abnormalities at baseline. Design: Data of 217 patients without pre-existing liver disease prospectively included in the COVID-19 registry of the LMU university hospital were analysed in order to assess the association of abnormal LFT at admission and course of the disease. Severe course was defined as admission to the intensive care unit (ICU) or as COVID-19-related death. Results: Abnormal LFT at baseline was present in 58% of patients, with a predominant elevation of aspartate aminotransferase (AST) (42%), gamma-glutamyltransferase (GGT) (37%) and alanine aminotransferase (ALT) (27%), hypoalbuminaemia was observed in 33%. Elevation of ALT and GGT, as well as hypoalbuminaemia, was associated with higher proportions of patients requiring ICU treatment and mechanical ventilation. After adjusting for age, gender and comorbidities, hypoalbuminaemia combined with abnormal AST or GGT at hospital admission was a highly significant independent risk factor for ICU admission (OR 46.22 and 38.8, respectively) and for a composite endpoint of ICU admission and/or COVID-19-related death (OR 42.0 and 26.9, respectively). Conclusion: Abnormal LFTs at hospital admission, in particular GGT and albumin, are associated with a severe course of SARS-CoV-2 infection.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Biomarkers/blood ; COVID-19/complications ; Female ; Hospitalization ; Humans ; Liver Diseases/virology ; Liver Function Tests ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; gamma-Glutamyltransferase/blood
Chemical Substances	Biomarkers ; gamma-Glutamyltransferase (EC 2.3.2.2) ; Aspartate Aminotransferases (EC 2.6.1.1) ; Alanine Transaminase (EC 2.6.1.2)
Language	English
Publishing date	2021-01-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2020-323800
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Article ; Online: Reply to eisenhut.

Muenchhoff, Maximilian / Goulder, Philip

The Journal of infectious diseases

2014 Volume 211, Issue 4, Page(s) 664–665

MeSH term(s)	Aging/immunology ; Communicable Diseases/immunology ; Disease Susceptibility ; Female ; Humans ; Male
Language	English
Publishing date	2014-08-26
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiu489
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Article ; Online: Omicron subvariants illustrate reduced respiratory tissue penetration, cell damage and inflammatory responses in human airway epithelia.

Zaderer, Viktoria / Abd El Halim, Hussam / Wyremblewsky, Anna-Lena / Lupoli, Gaia / Dächert, Christopher / Muenchhoff, Maximilian / Graf, Alexander / Blum, Helmut / Lass-Flörl, Cornelia / Keppler, Oliver T / Huber, Lukas A / Posch, Wilfried / Wilflingseder, Doris

Frontiers in immunology

2023 Volume 14, Page(s) 1258268

Abstract: Introduction: To explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue ... ...

Abstract	Introduction: To explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model. Methods: For this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses. Results and discussion: We observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.
MeSH term(s)	Humans ; Interleukin-6 ; Respiratory Insufficiency ; Epithelium ; Respiratory Mucosa ; Complement Activation
Chemical Substances	Interleukin-6
Language	English
Publishing date	2023-10-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1258268
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Article: How to exclude pulmonary embolism in patients hospitalized with COVID-19: a comparison of predictive scores.

Vielhauer, Jakob / Benesch, Christopher / Pernpruner, Anna / Johlke, Anna-Lena / Hellmuth, Johannes Christian / Muenchhoff, Maximilian / Scherer, Clemens / Fink, Nicola / Sabel, Bastian / Schulz, Christian / Mayerle, Julia / Mahajan, Ujjwal Mukund / Stubbe, Hans Christian

Thrombosis journal

2023 Volume 21, Issue 1, Page(s) 51

Abstract: Background: Pulmonary embolism (PE) is an important complication of Coronavirus disease 2019 (COVID-19). COVID-19 is associated with respiratory impairment and a pro-coagulative state, rendering PE more likely and difficult to recognize. Several ... ...

Abstract	Background: Pulmonary embolism (PE) is an important complication of Coronavirus disease 2019 (COVID-19). COVID-19 is associated with respiratory impairment and a pro-coagulative state, rendering PE more likely and difficult to recognize. Several decision algorithms relying on clinical features and D-dimer have been established. High prevalence of PE and elevated Ddimer in patients with COVID-19 might impair the performance of common decision algorithms. Here, we aimed to validate and compare five common decision algorithms implementing age adjusted Ddimer, the GENEVA, and Wells scores as well as the PEGeD- and YEARS-algorithms in patients hospitalized with COVID-19. Methods: In this single center study, we included patients who were admitted to our tertiary care hospital in the COVID-19 Registry of the LMU Munich. We retrospectively selected patients who received a computed tomography pulmonary angiogram (CTPA) or pulmonary ventilation/perfusion scintigraphy (V/Q) for suspected PE. The performances of five commonly used diagnostic algorithms (age-adjusted D-dimer, GENEVA score, PEGeD-algorithm, Wells score, and YEARS-algorithm) were compared. Results: We identified 413 patients with suspected PE who received a CTPA or V/Q confirming 62 PEs (15%). Among them, 358 patients with 48 PEs (13%) could be evaluated for performance of all algorithms. Patients with PE were older and their overall outcome was worse compared to patients without PE. Of the above five diagnostic algorithms, the PEGeD- and YEARS-algorithms performed best, reducing diagnostic imaging by 14% and 15% respectively with a sensitivity of 95.7% and 95.6%. The GENEVA score was able to reduce CTPA or V/Q by 32.2% but suffered from a low sensitivity (78.6%). Age-adjusted D-dimer and Wells score could not significantly reduce diagnostic imaging. Conclusion: The PEGeD- and YEARS-algorithms outperformed other tested decision algorithms and worked well in patients admitted with COVID-19. These findings need independent validation in a prospective study.
Language	English
Publishing date	2023-05-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2118392-2
ISSN	1477-9560
ISSN	1477-9560
DOI	10.1186/s12959-023-00492-5
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Article ; Online: Antiviral drugs block replication of highly immune-evasive Omicron subvariants ex vivo, but fail to reduce tissue inflammation.

Dichtl, Stefanie / Diem, Gabriel / Jäger, Michael / Zaderer, Viktoria / Lupoli, Gaia / Dächert, Christopher / Muenchhoff, Maximilian / Graf, Alexander / Blum, Helmut / Keppler, Oliver T / Lass-Flörl, Cornelia / Weiss, Günter / Wilflingseder, Doris / Posch, Wilfried

Antiviral research

2023 Volume 213, Page(s) 105581

Abstract: The identification of the SARS-CoV-2 Omicron variants BA.4/BA.5, BF.7 and BQ.1.1 immediately raised concerns regarding the efficacy of currently used monoclonal antibody therapies. Here we examined the activity of monoclonal antibody therapies and ... ...

Abstract	The identification of the SARS-CoV-2 Omicron variants BA.4/BA.5, BF.7 and BQ.1.1 immediately raised concerns regarding the efficacy of currently used monoclonal antibody therapies. Here we examined the activity of monoclonal antibody therapies and antiviral drugs against clinical specimens for SARS-CoV-2 Omicron BA.4/BA.5, BF.7 and BQ.1.1 employing an immunofluorescence neutralization assay. Further we explored treatment of BA.4/BA.5 infections with efficient antiviral drugs and monoclonal antibodies in a 3D model of primary human bronchial epithelial cells. We found that the antiviral drugs Molnupiravir, Nirmatrelvir and Remdesivir efficiently inhibit BA.4/BA.5, BF.7 and BQ.1.1 replication. In contrast, only the monoclonal antibody Cilgavimab exerted an inhibitory effect, while Tixagevimab, Regdanvimab and Sotrovimab lost their efficacy against BA.4/BA.5. We found that only the prophylactic treatment with Cilgavimab impacted on tissue inflammation by reducing intracellular complement component 3 (C3) activation following BA.4/BA.5 infection in primary human airway epithelial grown in air-liquid-interphase, which was not the case when using antiviral drugs or Cilgavimab after establishment of infection. Of note, all tested monoclonal antibodies had no neutralizing activity during infection by BF.7 and BQ.1.1 variants. Our results suggest that despite a marked reduction of viral replication, potent antiviral drugs fail to reduce tissue levels of inflammatory compounds such as C3, which can still result in tissue destruction.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Antibodies, Monoclonal ; Antibodies, Neutralizing/pharmacology ; Antiviral Agents/pharmacology ; Antibodies, Viral
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antiviral Agents ; Antibodies, Viral
Language	English
Publishing date	2023-03-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2023.105581
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Article ; Online: Salivary antibodies induced by BA.4/BA.5-convalescence or bivalent booster Immunoglobulin vaccination protect against novel SARS-COV-2 variants of concern.

Diem, Gabriel / Dichtl, Stefanie / Zaderer, Viktoria / Lass-Flörl, Cornelia / Reindl, Markus / Lupoli, Gaia / Dächert, Christopher / Muenchhoff, Maximilian / Graf, Alexander / Blum, Helmut / Keppler, Oliver T / Wilflingseder, Doris / Posch, Wilfried

Microbiology spectrum

2023 , Page(s) e0179323

Abstract: Currently, SARS-CoV-2 Omicron BA.5 subvariants BF.7 and BQ.1.1 are rapidly emerging worldwide. To evaluate the SARS-CoV-2-neutralizing capacity of sera and saliva from triple vaccinated individuals, either boosted with an adapted bivalent COVID-19 ... ...

Abstract	Currently, SARS-CoV-2 Omicron BA.5 subvariants BF.7 and BQ.1.1 are rapidly emerging worldwide. To evaluate the SARS-CoV-2-neutralizing capacity of sera and saliva from triple vaccinated individuals, either boosted with an adapted bivalent COVID-19 vaccine or recovered from BA.4/BA.5 infection, we analyzed the sensitivity of replication-competent SARS-CoV-2 Omicron subvariants BA.4/5, BQ.1.1 and BF.7 to neutralization. Analysis of SARS-CoV-2-specific IgGs and IgAs showed increased serum IgG titers in the vaccinated group, while the serum and salivary IgA levels were comparable. Similar and efficient serum neutralization against the ancestral strain of SARS-CoV-2 and Omicron BA.4/BA.5 was detected in both cohorts, but critically reduced for BQ.1.1 and BF.7. In contrast, salivary neutralization against BA.4/BA.5 was increased in the convalescent compared to the vaccinated group, while salivary neutralizing capacity against BQ.1.1 and BF.7 was comparable in these groups. Further, personalized protective effects studied in a human 3D respiratory model revealed the importance of salivary protection against different Omicron subvariants. IMPORTANCE In BA.4/BA.5-convalescent versus vaccinated groups, salivary neutralization capacity increased against SARS-CoV-2 Omicron BA.4/BA.5. In contrast, it neutralized novel Omicron subvariants BQ.1.1 and BF.7 similarly. Salivary protection against various Omicron subvariants was even more evident when tested in a personalized approach using highly differentiated respiratory human 3D models.
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01793-23
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