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Article ; Online: Monoclonal antibodies neutralizing alpha-hemolysin, bicomponent leukocidins, and clumping factor A protected against

Nguyen, Nhu T Q / Doan, Thien N M / Sato, Kei / Tkaczyk, Christine / Sellman, Bret R / Diep, Binh An

2023 Volume 14, Page(s) 1260627

Abstract: Background: Patients with septic shock caused by : Methods: Anesthetized rabbits were ventilated with lung-protective low-tidal volume, instrumented for advanced hemodynamic monitoring, and characterized for longitudinal changes in acute myocardial ... ...

Abstract	Background: Patients with septic shock caused by Methods: Anesthetized rabbits were ventilated with lung-protective low-tidal volume, instrumented for advanced hemodynamic monitoring, and characterized for longitudinal changes in acute myocardial dysfunction by echocardiography and sepsis-associated biomarkers after Results: Rabbits challenged with Conclusion: These results demonstrate the potential utility of a mechanically ventilated rabbit model that reproduced hallmark clinical features of hyperdynamic septic shock and the translational potential of immunotherapy targeting
MeSH term(s)	Humans ; Animals ; Rabbits ; Staphylococcus aureus ; Antibodies, Monoclonal/therapeutic use ; Hemolysin Proteins ; Leukocidins ; Shock, Septic/drug therapy ; Respiration, Artificial ; Stroke Volume ; Ventricular Function, Left ; Staphylococcal Infections ; Shock/drug therapy ; Immunoglobulin G
Chemical Substances	Antibodies, Monoclonal ; Hemolysin Proteins ; Leukocidins ; factor A ; Immunoglobulin G
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; 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.2023.1260627
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Article ; Online: Restoring polyamine levels by supplementation of spermidine modulates hepatic immune landscape in murine model of NASH.

Szydlowska, Marta / Lasky, Ginger / Oldham, Stephanie / Rivera, Cristian / Ford, Michael / Sellman, Bret R / Rhodes, Christopher J / Cohen, Taylor S

Biochimica et biophysica acta. Molecular basis of disease

2023 Volume 1869, Issue 6, Page(s) 166697

Abstract: Aims: To determine if changes in polyamines metabolism occur during non-alcoholic steatohepatitis (NASH) in human patients and mice, as well as to assess systemic and liver-specific effects of spermidine administration into mice suffering from advanced ... ...

Abstract	Aims: To determine if changes in polyamines metabolism occur during non-alcoholic steatohepatitis (NASH) in human patients and mice, as well as to assess systemic and liver-specific effects of spermidine administration into mice suffering from advanced NASH. Materials and methods: Human fecal samples were collected from 50 healthy and 50 NASH patients. For the preclinical studies C57Bl6/N male mice fed GAN or NIH-31 diet for 6 months were ordered from Taconic and liver biopsy was performed. Based on severity of liver fibrosis, body composition and body weight, the mice from both dietary groups were randomized into another two groups: half receiving 3 mM spermidine in drinking water, half normal water for subsequent 12 weeks. Body weight was measured weekly and glucose tolerance and body composition were assessed at the end. Blood and organs were collected during necropsy, and intrahepatic immune cells were isolated for flow cytometry analysis. Results: Metabolomic analysis of human and murine feces confirmed that levels of polyamines decreased along NASH progression. Administration of exogenous spermidine to the mice from both dietary groups did not affect body weight, body composition or adiposity. Moreover, incidence of macroscopic hepatic lesions was higher in NASH mice receiving spermidine. On the other hand, spermidine normalized numbers of Kupffer cells in the livers of mice suffering from NASH, although these beneficial effects did not translate into improved liver steatosis or fibrosis severity. Conclusion: Levels of polyamines decrease during NASH in mice and human patients but spermidine administration does not improve advanced NASH.
MeSH term(s)	Humans ; Male ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism ; Spermidine/pharmacology ; Disease Models, Animal ; Polyamines ; Diet, High-Fat ; Body Weight ; Dietary Supplements
Chemical Substances	Spermidine (U87FK77H25) ; Polyamines
Language	English
Publishing date	2023-04-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2023.166697
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Article: A fungal metabolic regulator underlies infectious synergism during

Paul, Saikat / Todd, Olivia A / Eichelberger, Kara R / Tkaczyk, Christine / Sellman, Bret R / Noverr, Mairi C / Cassat, James E / Fidel, Paul L / Peters, Brian M

bioRxiv : the preprint server for biology

2024

Abstract: ... Candida ... ...

Abstract	Candida albicans
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.15.580531
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Article ; Online: Antibiotics and Immunotherapy: Too Much of Anything is Bad!

Gopalakrishnan, Vancheswaran / Sellman, Bret R / Cohen, Taylor S / Dennis, Phillip A

European urology

2020 Volume 78, Issue 4, Page(s) 544–545

MeSH term(s)	Anti-Bacterial Agents/adverse effects ; Antibodies, Monoclonal, Humanized ; Humans ; Immunologic Factors ; Immunotherapy/adverse effects
Chemical Substances	Anti-Bacterial Agents ; Antibodies, Monoclonal, Humanized ; Immunologic Factors ; atezolizumab (52CMI0WC3Y)
Language	English
Publishing date	2020-08-15
Publishing country	Switzerland
Document type	Editorial ; Comment
ZDB-ID	193790-x
ISSN	1873-7560 ; 1421-993X ; 0302-2838
ISSN (online)	1873-7560 ; 1421-993X
ISSN	0302-2838
DOI	10.1016/j.eururo.2020.07.027
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Article ; Online: Neutralizing Staphylococcus aureus Virulence with AZD6389, a Three mAb Combination, Accelerates Closure of a Diabetic Polymicrobial Wound.

Tkaczyk, Christine / Jones-Nelson, Omari / Shi, Yue Yue / Tabor, David E / Cheng, Lily / Zhang, Tianhui / Sellman, Bret R

mSphere

2022 Volume 7, Issue 3, Page(s) e0013022

Abstract: Nonhealing diabetic foot ulcers (DFU), a major complication of diabetes, are associated with high morbidity and mortality despite current standard of care. Since Staphylococcus aureus is the most common pathogen isolated from nonhealing and infected DFU, ...

Abstract	Nonhealing diabetic foot ulcers (DFU), a major complication of diabetes, are associated with high morbidity and mortality despite current standard of care. Since Staphylococcus aureus is the most common pathogen isolated from nonhealing and infected DFU, we hypothesized that S. aureus virulence factors would damage tissue, promote immune evasion and alter the microbiome, leading to bacterial persistence and delayed wound healing. In a diabetic mouse polymicrobial wound model with S. aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, we report a rapid bacterial proliferation, prolonged pro-inflammatory response and large necrotic lesions unclosed for up to 40 days. Treatment with AZD6389, a three-monoclonal antibody combination targeting S. aureus alpha toxin, 4 secreted leukotoxins, and fibrinogen binding cell-surface adhesin clumping factor A resulted in full skin re-epithelization 21 days after inoculation. By neutralizing multiple virulence factors, AZD6389 effectively blocked bacterial agglutination and S. aureus-mediated cell killing, abrogated S. aureus-mediated immune evasion and targeted the bacteria for opsonophagocytic killing. Neutralizing S. aureus virulence not only facilitated S. aureus clearance in lesions, but also reduced S. pyogenes and P. aeruginosa numbers, damaging inflammatory mediators and markers for neutrophil extracellular trap formation 14 days post initiation. Collectively, our data suggest that AZD6389 holds promise as an immunotherapeutic approach against DFU complications.
MeSH term(s)	Animals ; Antibodies, Monoclonal ; Bacteria ; Diabetes Mellitus ; Diabetic Foot/complications ; Diabetic Foot/drug therapy ; Mice ; Pseudomonas aeruginosa ; Quality of Life ; Staphylococcal Infections/microbiology ; Staphylococcus aureus ; Virulence ; Virulence Factors
Chemical Substances	Antibodies, Monoclonal ; Virulence Factors
Language	English
Publishing date	2022-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/msphere.00130-22
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Article ; Online: A protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens.

Yan, Jun / Nielsen, Travis B / Lu, Peggy / Talyansky, Yuli / Slarve, Matt / Reza, Hernan / Novakovic, Boris / Netea, Mihai G / Keller, Ashley E / Warren, Troy / DiGiandomenico, Antonio / Sellman, Bret R / Luna, Brian M / Spellberg, Brad

Science translational medicine

2023 Volume 15, Issue 716, Page(s) eadf9556

Abstract: Traditional vaccines are difficult to deploy against the diverse antimicrobial-resistant, nosocomial pathogens that cause health care-associated infections. We developed a protein-free vaccine composed of aluminum hydroxide, monophosphoryl lipid A, and ... ...

Abstract	Traditional vaccines are difficult to deploy against the diverse antimicrobial-resistant, nosocomial pathogens that cause health care-associated infections. We developed a protein-free vaccine composed of aluminum hydroxide, monophosphoryl lipid A, and fungal mannan that improved survival and reduced bacterial burden of mice with invasive blood or lung infections caused by methicillin-resistant
MeSH term(s)	Animals ; Mice ; Anti-Bacterial Agents/pharmacology ; Methicillin-Resistant Staphylococcus aureus ; Cross Infection/prevention & control ; Cross Infection/microbiology ; Anti-Infective Agents/pharmacology ; Vaccines ; Immunity, Innate ; Microbial Sensitivity Tests ; Drug Resistance, Bacterial
Chemical Substances	Anti-Bacterial Agents ; Anti-Infective Agents ; Vaccines
Language	English
Publishing date	2023-10-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adf9556
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Article: Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen

Gopalakrishnan, Vancheswaran / Dozier, Elizabeth Ashley / Glover, Matthew S. / Novick, Steven / Ford, Michael / Morehouse, Christopher / Warrener, Paul / Caceres, Carolina / Hess, Sonja / Sellman, Bret R. / Cohen, Taylor S.

Microorganisms. 2021 June 29, v. 9, no. 7

2021

Abstract: The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature ... ...

Abstract	The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fecal microbiota transplant (FMT) engraftment in conventional mice are yet to be established. Conventional BALB/c mice were randomized to receive 3-day (3d) or 3-week (3w) antibiotic (ABX) regimen in their drinking water followed by 1 or 5-daily FMTs from a human donor. Fecal samples were collected longitudinally and characterized using 16S ribosomal RNA (rRNA) sequencing. Semi-targeted metabolomic profiling of fecal samples was also done with liquid chromatography–mass spectrometry (LC-MS). Lastly, we sought to confirm our findings in BKS mice. Recovery of baseline diversity scores were greatest in the 3d groups, driven by re-emergence of mouse commensal microbiota, whereas the most resemblance to donor microbiota was seen in the 3w + 5-FMT group. Amplicon sequence variants (ASVs) that were linked to the input material (human ASVs) engrafted to a significantly greater extent when compared to mouse ASVs in the 3-week groups but not the 3-day groups. Lastly, comparison of metabolomic profiles revealed distinct functional profiles by ABX regimen. These results indicate successful model optimization and emphasize the importance of ABX duration and frequency of FMT dosing; the most stable and reliable colonization by donor ASVs was seen in the 3wk + 5-FMT group.
Keywords	antibiotics ; human physiology ; humans ; immune system ; intestinal microorganisms ; liquid chromatography ; mass spectrometry ; metabolomics ; mice ; microbiome ; ribosomal RNA
Language	English
Dates of publication	2021-0629
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9071399
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Early diagnostic BioMARKers in exacerbations of chronic obstructive pulmonary disease: protocol of the exploratory, prospective, longitudinal, single-centre, observational MARKED study.

Waeijen-Smit, Kiki / DiGiandomenico, Antonio / Bonnell, Jessica / Ostridge, Kristoffer / Gehrmann, Ulf / Sellman, Bret R / Kenny, Tara / van Kuijk, Sander / Peerlings, Daphne / Spruit, Martijn A / Simons, Sami O / Houben-Wilke, Sarah / Franssen, Frits M E

BMJ open

2023 Volume 13, Issue 3, Page(s) e068787

Abstract: Introduction: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) play a pivotal role in the burden and progressive course of chronic obstructive pulmonary disease (COPD). As such, disease management is predominantly based on the ... ...

Abstract	Introduction: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) play a pivotal role in the burden and progressive course of chronic obstructive pulmonary disease (COPD). As such, disease management is predominantly based on the prevention of these episodes of acute worsening of respiratory symptoms. However, to date, personalised prediction and early and accurate diagnosis of AECOPD remain unsuccessful. Therefore, the current study was designed to explore which frequently measured biomarkers can predict an AECOPD and/or respiratory infection in patients with COPD. Moreover, the study aims to increase our understanding of the heterogeneity of AECOPD as well as the role of microbial composition and hostmicrobiome interactions to elucidate new disease biology in COPD. Methods and analysis: The 'Early diagnostic BioMARKers in Exacerbations of COPD' study is an exploratory, prospective, longitudinal, single-centre, observational study with 8-week follow-up enrolling up to 150 patients with COPD admitted to inpatient pulmonary rehabilitation at Ciro (Horn, the Netherlands). Respiratory symptoms, vitals, spirometry and nasopharyngeal, venous blood, spontaneous sputum and stool samples will be frequently collected for exploratory biomarker analysis, longitudinal characterisation of AECOPD (ie, clinical, functional and microbial) and to identify host-microbiome interactions. Genomic sequencing will be performed to identify mutations associated with increased risk of AECOPD and microbial infections. Predictors of time-to-first AECOPD will be modelled using Cox proportional hazards' regression. Multiomic analyses will provide a novel integration tool to generate predictive models and testable hypotheses about disease causation and predictors of disease progression. Ethics and dissemination: This protocol was approved by the Medical Research Ethics Committees United (MEC-U), Nieuwegein, the Netherlands (NL71364.100.19). Trial registration number: NCT05315674.
MeSH term(s)	Humans ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; Disease Management ; Disease Progression ; Hospitalization ; Observational Studies as Topic
Language	English
Publishing date	2023-03-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-068787
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Article ; Online: Antibacterial monoclonal antibodies: the next generation?

DiGiandomenico, Antonio / Sellman, Bret R

Current opinion in microbiology

2015 Volume 27, Page(s) 78–85

Abstract: There is a clear need for renewed efforts to combat the increasing incidence of antibiotic resistance. While the antibiotic resistance epidemic is due in part to the misuse of antibiotics, even proper empiric antibiotic therapy increases the selective ... ...

Abstract	There is a clear need for renewed efforts to combat the increasing incidence of antibiotic resistance. While the antibiotic resistance epidemic is due in part to the misuse of antibiotics, even proper empiric antibiotic therapy increases the selective pressure and potential for drug-resistance and spread of resistance mechanisms between bacteria. Antibiotic resistance coupled with the detrimental effects of broad-spectrum antibiotics on the healthy microbiome, have led the field to explore pathogen specific antibacterials such as monoclonal antibodies (mAbs). Medical need along with advances in mAb discovery, engineering, and production have driven significant effort developing mAb-based antibacterials. If successful, they will provide physicians with precision weapons to combat bacterial infections and can help prevent a return to a pre-antibiotic era.
MeSH term(s)	Anti-Bacterial Agents/immunology ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Bacteria/drug effects ; Bacteria/immunology ; Bacterial Infections/drug therapy ; Bacterial Infections/immunology ; Bacterial Infections/microbiology ; Drug Discovery ; Drug Resistance, Microbial/immunology ; Humans ; Microbiota/drug effects ; Microbiota/immunology
Chemical Substances	Anti-Bacterial Agents ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1418474-6
ISSN	1879-0364 ; 1369-5274
ISSN (online)	1879-0364
ISSN	1369-5274
DOI	10.1016/j.mib.2015.07.014
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Zs.A 5514: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit.

Lee, Chiyun / Lin, Junxia / Prokop, Andrzej / Gopalakrishnan, Vancheswaran / Hanna, Richard N / Papa, Eliseo / Freeman, Adrian / Patel, Saleha / Yu, Wen / Huhn, Monika / Sheikh, Abdul-Saboor / Tan, Keith / Sellman, Bret R / Cohen, Taylor / Mangion, Jonathan / Khan, Faisal M / Gusev, Yuriy / Shameer, Khader

Frontiers in genetics

2022 Volume 13, Page(s) 868015

Abstract: Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods ... ...

Abstract	Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope. Developing hybrid intelligence solutions that combine human intelligence in the scientific domain and disease biology with the ability to mine multiple databases simultaneously may help augment drug target discovery and identify novel drug-indication associations. We believe that integrating different data sources using a singular numerical scoring system in a hybrid intelligent framework could help to bridge these different omics layers and facilitate rapid drug target prioritization for studies in drug discovery, development or repositioning. Herein, we describe our prototype of the StarGazer pipeline which combines multi-source, multi-omics data with a novel target prioritization scoring system in an interactive Python-based Streamlit dashboard. StarGazer displays target prioritization scores for genes associated with 1844 phenotypic traits, and is available via https://github.com/AstraZeneca/StarGazer.
Language	English
Publishing date	2022-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2022.868015
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