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Book ; Online: Oxidative Stress in Aging

Miwa, Satomi / Beckman, Kenneth B. / Muller, Florian L.

From Model Systems to Human Diseases

2008

Author's details	edited by Satomi Miwa, Kenneth B. Beckman, Florian L. Muller
Keywords	Cell biology ; Geriatrics ; Internal medicine
Language	English
Publisher	Humana Press, a part of Springer Science + Business Media, LLC
Publishing place	Totowa, NJ
Document type	Book ; Online
HBZ-ID	TT050387208
ISBN	978-1-588-29991-8 ; 978-1-597-45420-9 ; 1-588-29991-0 ; 1-597-45420-6
DOI	10.1007/978-1-59745-420-9
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Mycobacterium tuberculosis Requires the Outer Membrane Lipid Phthiocerol Dimycocerosate for Starvation-Induced Antibiotic Tolerance.

Block, Alisha M / Namugenyi, Sarah B / Palani, Nagendra P / Brokaw, Alyssa M / Zhang, Leanne / Beckman, Kenneth B / Tischler, Anna D

mSystems

2023 Volume 8, Issue 1, Page(s) e0069922

Abstract: Tolerance of Mycobacterium tuberculosis to antibiotics contributes to the long duration of tuberculosis (TB) treatment and the emergence of drug-resistant strains. M. tuberculosis drug tolerance is induced by nutrient restriction, but the genetic ... ...

Abstract	Tolerance of Mycobacterium tuberculosis to antibiotics contributes to the long duration of tuberculosis (TB) treatment and the emergence of drug-resistant strains. M. tuberculosis drug tolerance is induced by nutrient restriction, but the genetic determinants that promote antibiotic tolerance triggered by nutrient limitation have not been comprehensively identified. Here, we show that M. tuberculosis requires production of the outer membrane lipid phthiocerol dimycocerosate (PDIM) to tolerate antibiotics under nutrient-limited conditions. We developed an arrayed transposon (Tn) mutant library in M. tuberculosis Erdman and used orthogonal pooling and transposon sequencing (Tn-seq) to map the locations of individual mutants in the library. We screened a subset of the library (~1,000 mutants) by Tn-seq and identified 32 and 102 Tn mutants with altered tolerance to antibiotics under stationary-phase and phosphate-starved conditions, respectively. Two mutants recovered from the arrayed library,
MeSH term(s)	Humans ; Membrane Lipids/chemistry ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Tuberculosis ; Drug Resistance, Bacterial
Chemical Substances	Membrane Lipids ; phthiocerol dimycocerosate (63642-22-8)
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-5077
ISSN (online)	2379-5077
DOI	10.1128/msystems.00699-22
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Article ; Online: Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.

Perez-Garcia, Javier / Pino-Yanes, Maria / Plender, Elizabeth G / Everman, Jamie L / Eng, Celeste / Jackson, Nathan D / Moore, Camille M / Beckman, Kenneth B / Medina, Vivian / Sharma, Sunita / Winnica, Daniel Efrain / Holguin, Fernando / Rodríguez-Santana, José / Villar, Jesús / Ziv, Elad / Seibold, Max A / Burchard, Esteban G

Clinical epigenetics

2023 Volume 15, Issue 1, Page(s) 156

Abstract: Background: Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could ... ...

Abstract	Background: Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables. Results: We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p < 9 × 10 Conclusions: This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma.
MeSH term(s)	Child ; Humans ; DNA Methylation ; Epigenomics ; Asthma/drug therapy ; Asthma/genetics ; Albuterol/pharmacology ; Albuterol/therapeutic use ; Epigenesis, Genetic ; Bronchodilator Agents/pharmacology ; Bronchodilator Agents/therapeutic use ; Epithelial Cells ; Genome-Wide Association Study
Chemical Substances	Albuterol (QF8SVZ843E) ; Bronchodilator Agents
Language	English
Publishing date	2023-10-03
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-023-01571-0
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Article ; Online: Novel insights into the whole-blood DNA methylome of asthma in ethnically diverse children and youth.

Herrera-Luis, Esther / Rosa-Baez, Carlos / Huntsman, Scott / Eng, Celeste / Beckman, Kenneth B / LeNoir, Michael A / Rodriguez-Santana, Jose R / Villar, Jesús / Laprise, Catherine / Borrell, Luisa N / Ziv, Elad / Burchard, Esteban G / Pino-Yanes, Maria

The European respiratory journal

2023 Volume 62, Issue 6

Abstract: Background: The epigenetic mechanisms of asthma remain largely understudied in African Americans and Hispanics/Latinos, two populations disproportionately affected by asthma. We aimed to identify markers, regions and processes with differential patterns ...

Abstract	Background: The epigenetic mechanisms of asthma remain largely understudied in African Americans and Hispanics/Latinos, two populations disproportionately affected by asthma. We aimed to identify markers, regions and processes with differential patterns of DNA methylation (DNAm) in whole blood by asthma status in ethnically diverse children and youth, and to assess their functional consequences. Methods: DNAm levels were profiled with the Infinium MethylationEPIC or HumanMethylation450 BeadChip arrays among 1226 African Americans or Hispanics/Latinos and assessed for differential methylation per asthma status at the CpG and region (differentially methylated region (DMR)) level. Novel associations were validated in blood and/or nasal epithelium from ethnically diverse children and youth. The functional and biological implications of the markers identified were investigated by combining epigenomics with transcriptomics from study participants. Results: 128 CpGs and 196 DMRs were differentially methylated after multiple testing corrections, including 92.3% and 92.8% novel associations, respectively. 41 CpGs were replicated in other Hispanics/Latinos, prioritising cg17647904 ( Conclusions: We report novel whole-blood DNAm markers for asthma underlying key processes of the disease pathophysiology and confirm the transferability of previous asthma DNAm associations to ethnically diverse populations.
MeSH term(s)	Child ; Humans ; Adolescent ; Epigenome ; Epigenesis, Genetic ; Asthma/genetics ; DNA Methylation ; Gene Expression Profiling ; NADPH Dehydrogenase/genetics
Chemical Substances	NDUFA12 protein, human ; NADPH Dehydrogenase (EC 1.6.99.1)
Language	English
Publishing date	2023-12-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.00714-2023
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Zs.A 2322: 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 ; Online: A rapid, cost-effective tailed amplicon method for sequencing SARS-CoV-2.

Gohl, Daryl M / Garbe, John / Grady, Patrick / Daniel, Jerry / Watson, Ray H B / Auch, Benjamin / Nelson, Andrew / Yohe, Sophia / Beckman, Kenneth B

BMC genomics

2020 Volume 21, Issue 1, Page(s) 863

Abstract: Background: The global COVID-19 pandemic has led to an urgent need for scalable methods for clinical diagnostics and viral tracking. Next generation sequencing technologies have enabled large-scale genomic surveillance of SARS-CoV-2 as thousands of ... ...

Abstract	Background: The global COVID-19 pandemic has led to an urgent need for scalable methods for clinical diagnostics and viral tracking. Next generation sequencing technologies have enabled large-scale genomic surveillance of SARS-CoV-2 as thousands of isolates are being sequenced around the world and deposited in public data repositories. A number of methods using both short- and long-read technologies are currently being applied for SARS-CoV-2 sequencing, including amplicon approaches, metagenomic methods, and sequence capture or enrichment methods. Given the small genome size, the ability to sequence SARS-CoV-2 at scale is limited by the cost and labor associated with making sequencing libraries. Results: Here we describe a low-cost, streamlined, all amplicon-based method for sequencing SARS-CoV-2, which bypasses costly and time-consuming library preparation steps. We benchmark this tailed amplicon method against both the ARTIC amplicon protocol and sequence capture approaches and show that an optimized tailed amplicon approach achieves comparable amplicon balance, coverage metrics, and variant calls to the ARTIC v3 approach. Conclusions: The tailed amplicon method we describe represents a cost-effective and highly scalable method for SARS-CoV-2 sequencing.
MeSH term(s)	Benchmarking ; COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/virology ; COVID-19 Nucleic Acid Testing/methods ; COVID-19 Nucleic Acid Testing/standards ; Genome, Viral/genetics ; Humans ; Molecular Epidemiology ; Mutation ; RNA, Viral/genetics ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Sequence Analysis/methods ; Sequence Analysis/standards
Chemical Substances	RNA, Viral
Language	English
Publishing date	2020-12-04
Publishing country	England
Document type	Journal Article
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/s12864-020-07283-6
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Article ; Online: Leukocyte telomere length, cancer incidence and all-cause mortality among Chinese adults: Singapore Chinese Health Study.

Samavat, Hamed / Luu, Hung N / Beckman, Kenneth B / Jin, Aizhen / Wang, Renwei / Koh, Woon-Puay / Yuan, Jian-Min

International journal of cancer

2020 Volume 148, Issue 2, Page(s) 352–362

Abstract: Telomeres play a key role in chromosomal maintenance and stability. To date, few studies have investigated the association of leukocyte telomere length with risk of cancer incidence and all-cause mortality in a large prospective cohort, particularly of ... ...

Abstract	Telomeres play a key role in chromosomal maintenance and stability. To date, few studies have investigated the association of leukocyte telomere length with risk of cancer incidence and all-cause mortality in a large prospective cohort, particularly of the Asian population. Relative telomere lengths in genomic DNA from peripheral blood samples were quantified using a validated quantitative real-time PCR among 26 540 middle-aged or older Chinese adults. Hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer and deaths by quintiles of telomere length were calculated using the Cox proportional hazards regression method with adjustment for age, sex and other potential confounders. After baseline blood collection, 4353 persons developed cancer and 7609 died. Participants with the longest decile of telomeres had a 26% (95% CI: 11%-44%) higher risk of total cancer incidence compared to the shortest decile after controlling for age, sex and other potential founders (P
MeSH term(s)	Aged ; Asian People ; China/ethnology ; Cohort Studies ; DNA/blood ; DNA/genetics ; Female ; Humans ; Incidence ; Leukocytes/ultrastructure ; Male ; Middle Aged ; Neoplasms/blood ; Neoplasms/epidemiology ; Neoplasms/genetics ; Neoplasms/mortality ; Prospective Studies ; Singapore/epidemiology ; Telomere/genetics
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2020-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.33211
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 576: Show issues

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Article ; Online: Epigenome-wide association study of lung function in Latino children and youth with asthma.

Herrera-Luis, Esther / Li, Annie / Mak, Angel C Y / Perez-Garcia, Javier / Elhawary, Jennifer R / Oh, Sam S / Hu, Donglei / Eng, Celeste / Keys, Kevin L / Huntsman, Scott / Beckman, Kenneth B / Borrell, Luisa N / Rodriguez-Santana, Jose / Burchard, Esteban G / Pino-Yanes, Maria

Clinical epigenetics

2022 Volume 14, Issue 1, Page(s) 9

Abstract: Introduction: DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association ... ...

Abstract	Introduction: DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population. Here, we aimed to identify DNA methylation patterns associated with lung function in pediatric asthma among Latinos. Results: We conducted an EWAS in whole blood from 250 Puerto Rican and 148 Mexican American children and young adults with asthma. A total of five CpGs exceeded the genome-wide significance threshold of p = 1.17 × 10 Conclusions: We replicated previous associations of epigenetic markers with lung function in whole blood and identified novel population-specific associations shared among Latino subgroups.
MeSH term(s)	Adolescent ; Adult ; Asthma/genetics ; Asthma/physiopathology ; Child ; DNA Methylation/genetics ; Epigenesis, Genetic ; Epigenome ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Hispanic or Latino/genetics ; Humans ; Male ; United States/epidemiology ; Young Adult
Language	English
Publishing date	2022-01-15
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-022-01227-5
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Article ; Online: Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants.

Kuo, Chia-Ling / Pilling, Luke C / Atkins, Janice L / Masoli, Jane A H / Delgado, João / Tignanelli, Christopher / Kuchel, George A / Melzer, David / Beckman, Kenneth B / Levine, Morgan E

The journals of gerontology. Series A, Biological sciences and medical sciences

2021 Volume 76, Issue 8, Page(s) e133–e141

Abstract: Background: Age and disease prevalence are the 2 biggest risk factors for Coronavirus disease 2019 (COVID-19) symptom severity and death. We therefore hypothesized that increased biological age, beyond chronological age, may be driving disease-related ... ...

Abstract	Background: Age and disease prevalence are the 2 biggest risk factors for Coronavirus disease 2019 (COVID-19) symptom severity and death. We therefore hypothesized that increased biological age, beyond chronological age, may be driving disease-related trends in COVID-19 severity. Methods: Using the UK Biobank England data, we tested whether a biological age estimate (PhenoAge) measured more than a decade prior to the COVID-19 pandemic was predictive of 2 COVID-19 severity outcomes (inpatient test positivity and COVID-19-related mortality with inpatient test-confirmed COVID-19). Logistic regression models were used with adjustment for age at the pandemic, sex, ethnicity, baseline assessment centers, and preexisting diseases/conditions. Results: Six hundred and thirteen participants tested positive at inpatient settings between March 16 and April 27, 2020, 154 of whom succumbed to COVID-19. PhenoAge was associated with increased risks of inpatient test positivity and COVID-19-related mortality (ORMortality = 1.63 per 5 years, 95% CI: 1.43-1.86, p = 4.7 × 10-13) adjusting for demographics including age at the pandemic. Further adjustment for preexisting diseases/conditions at baseline (ORM = 1.50, 95% CI: 1.30-1.73 per 5 years, p = 3.1 × 10-8) and at the early pandemic (ORM = 1.21, 95% CI: 1.04-1.40 per 5 years, p = .011) decreased the association. Conclusions: PhenoAge measured in 2006-2010 was associated with COVID-19 severity outcomes more than 10 years later. These associations were partly accounted for by prevalent chronic diseases proximate to COVID-19 infection. Overall, our results suggest that aging biomarkers, like PhenoAge may capture long-term vulnerability to diseases like COVID-19, even before the accumulation of age-related comorbid conditions.
MeSH term(s)	Aged ; Aging/physiology ; Biological Specimen Banks ; Biomarkers ; COVID-19/epidemiology ; COVID-19 Testing/statistics & numerical data ; Chronic Disease ; Humans ; Middle Aged ; Models, Statistical ; Mortality/trends ; Preexisting Condition Coverage/statistics & numerical data ; SARS-CoV-2/isolation & purification ; Severity of Illness Index ; Time Factors ; United Kingdom/epidemiology
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glab060
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Article ; Online: Dissecting and tuning primer editing by proofreading polymerases.

Gohl, Daryl M / Auch, Benjamin / Certano, Amanda / LeFrançois, Brice / Bouevitch, Anne / Doukhanine, Evgueni / Fragel, Christina / Macklaim, Jean / Hollister, Emily / Garbe, John / Beckman, Kenneth B

Nucleic acids research

2021 Volume 49, Issue 15, Page(s) e87

Abstract: Proofreading polymerases have 3' to 5' exonuclease activity that allows the excision and correction of mis-incorporated bases during DNA replication. In a previous study, we demonstrated that in addition to correcting substitution errors and lowering the ...

Abstract	Proofreading polymerases have 3' to 5' exonuclease activity that allows the excision and correction of mis-incorporated bases during DNA replication. In a previous study, we demonstrated that in addition to correcting substitution errors and lowering the error rate of DNA amplification, proofreading polymerases can also edit PCR primers to match template sequences. Primer editing is a feature that can be advantageous in certain experimental contexts, such as amplicon-based microbiome profiling. Here we develop a set of synthetic DNA standards to report on primer editing activity and use these standards to dissect this phenomenon. The primer editing standards allow next-generation sequencing-based enzymological measurements, reveal the extent of editing, and allow the comparison of different polymerases and cycling conditions. We demonstrate that proofreading polymerases edit PCR primers in a concentration-dependent manner, and we examine whether primer editing exhibits any sequence specificity. In addition, we use these standards to show that primer editing is tunable through the incorporation of phosphorothioate linkages. Finally, we demonstrate the ability of primer editing to robustly rescue the drop-out of taxa with 16S rRNA gene-targeting primer mismatches using mock communities and human skin microbiome samples.
MeSH term(s)	DNA Primers/genetics ; DNA Replication/genetics ; DNA-Directed DNA Polymerase/genetics ; Exonucleases/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/genetics ; Nucleic Acid Amplification Techniques/methods ; RNA, Ribosomal, 16S/genetics ; Skin/microbiology
Chemical Substances	DNA Primers ; RNA, Ribosomal, 16S ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Exonucleases (EC 3.1.-)
Language	English
Publishing date	2021-06-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkab471
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Article ; Online: Neither Donor nor Recipient Mitochondrial Haplotypes Are Associated with Unrelated Donor Transplant Outcomes: A Validation Study from the CIBMTR.

Spector, Logan G / Spellman, Stephen R / Thyagarajan, Bharat / Beckman, Kenneth B / Hoffmann, Cody / Garbe, John / Hahn, Theresa / Sucheston-Campbell, Lara / Richardson, Michaela / De For, Todd E / Tolar, Jakub / Verneris, Michael R

Transplantation and cellular therapy

2021 Volume 27, Issue 10, Page(s) 836.e1–836.e7

Abstract: Graft-versus-host-disease (GVHD) is a multistep process that involves T-cell recognition and priming toward alloantigen, expansion, acquisition of effector function, and repeated tissue injury, resulting in clinical manifestations of the disease. All of ... ...

Abstract	Graft-versus-host-disease (GVHD) is a multistep process that involves T-cell recognition and priming toward alloantigen, expansion, acquisition of effector function, and repeated tissue injury, resulting in clinical manifestations of the disease. All of these processes have considerable metabolic demands and understanding the key role of mitochondria in cellular metabolism as it relates to GVHD has increased significantly. Mitochondrial DNA (mtDNA) haplotypes have been linked to functional differences in vitro, suggesting they have functional differences at an organismal level. We previously used mtDNA typing to assess the impact of mtDNA haplotypes on outcomes of ~400 allo-HCT patients. This pilot study identified uncommon mtDNA haplotypes potentially associated with inferior outcomes. We sought to validate pilot findings of associations between donor and recipient mitochondrial haplotypes and transplant outcome. We examined a cohort of 4143 donor-recipient pairs obtained from the Center for International Blood and Marrow Transplant Research. MtDNA was extracted from whole blood or peripheral blood mononuclear cells from donors and recipients and sequenced to discern haplotype. We used multiple regression analysis to examine the independent association of mtDNA haplotype with overall survival and grade III-IV acute GVHD (aGVHD) adjusting for known risk factors for poor transplant outcome. Neither recipient nor donor mtDNA haplotype reached groupwise significance for overall survival (P =.26 and .39, respectively) or grade III-IV aGVHD (P = .68 and.57, respectively). Adjustment for genomically determined ancestry in the subset of donor-recipient pairs for which this was available did not materially change results. We conclude that our original finding was due to chance in a small sample size and that there is essentially no evidence that mtDNA haplotype or haplotype mismatch contributes to risk of serious outcomes after allogeneic transplantation.
MeSH term(s)	Haplotypes ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukocytes, Mononuclear ; Mitochondria ; Pilot Projects ; Unrelated Donors
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2021.06.019
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