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  1. Article ; Online: Characterization of a novel mouse platelet transfusion model.

    Gordy, Dominique / Swayne, Theresa / Berry, Gregory J / Thomas, Tiffany A / Hudson, Krystalyn E / Stone, Elizabeth F

    Vox sanguinis

    2024  

    Abstract: Background and objectives: Platelet transfusions are increasing with medical advances. Based on FDA criteria, platelet units are assessed by in vitro measures; however, it is not known how platelet processing and storage duration affect function in vivo. ...

    Abstract Background and objectives: Platelet transfusions are increasing with medical advances. Based on FDA criteria, platelet units are assessed by in vitro measures; however, it is not known how platelet processing and storage duration affect function in vivo. Our study's aim was to develop a novel platelet transfusion model stored in mouse plasma that meets FDA criteria adapted to mice, and transfused fresh and stored platelets are detectable in clots in vivo.
    Study design and methods: Platelet units stored in mouse plasma were prepared using a modified platelet-rich plasma (PRP) collection protocol. Characteristics of fresh and stored units, including pH, cell count, in vitro measures of activity, including activation and aggregation, and post-transfusion recovery (PTR), were determined. Lastly, a tail transection assay was conducted using mice transfused with fresh or stored units, and transfused platelets were identified by confocal imaging.
    Results: Platelet units had acceptable platelet and white cell counts and were negative for bacterial contamination. Fresh and 1-day stored units had acceptable pH; the platelets were activatable by thrombin and adenosine diphosphate, agreeable with thrombin, had acceptable PTR, and were present in vivo in clots of recipients after tail transection. In contrast, 2-day stored units had clinically unacceptable quality.
    Conclusion: We developed mouse platelets for transfusion analogous to human platelet units using a modified PRP collection protocol with maximum storage of 1 day for an 'old' unit. This provides a powerful tool to test how process modifications and storage conditions affect transfused platelet function in vivo.
    Language English
    Publishing date 2024-04-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 80313-3
    ISSN 1423-0410 ; 0042-9007
    ISSN (online) 1423-0410
    ISSN 0042-9007
    DOI 10.1111/vox.13642
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Hitchhiker's guide to the red blood cell storage lesion.

    Thomas, Tiffany / Spitalnik, Steven L

    Blood transfusion = Trasfusione del sangue

    2019  Volume 17, Issue 1, Page(s) 1–3

    MeSH term(s) Blood Preservation ; Erythrocytes ; Humans
    Language English
    Publishing date 2019-01-09
    Publishing country Italy
    Document type Editorial ; Comment
    ZDB-ID 2135732-8
    ISSN 2385-2070 ; 0041-1787 ; 1723-2007
    ISSN (online) 2385-2070
    ISSN 0041-1787 ; 1723-2007
    DOI 10.2450/2019.0257-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Characterization of a Novel Mouse Platelet Transfusion Model.

    Gordy, Dominique / Swayne, Theresa / Berry, Gregory J / Thomas, Tiffany A / Hudson, Krystalyn E / Stone, Elizabeth F

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Background: Platelet transfusions are increasing with advances in medical care. Based on FDA criteria, platelet units are assessed by : Study design and methods: Platelet units stored in mouse plasma were prepared using a modified platelet rich ... ...

    Abstract Background: Platelet transfusions are increasing with advances in medical care. Based on FDA criteria, platelet units are assessed by
    Study design and methods: Platelet units stored in mouse plasma were prepared using a modified platelet rich plasma collection protocol. Characteristics of fresh and stored units, including pH, cell count,
    Results: Platelet units had acceptable platelet and white cell counts and were negative for bacterial contamination. Fresh and 1-day stored units had acceptable pH; the platelets were activatable by thrombin and ADP, aggregable with thrombin, had acceptable PTR, and were present
    Discussion: We developed mouse platelets for transfusion analogous to human platelet units using a modified platelet rich plasma collection protocol with maximum storage of 1 day for an "old" unit. This provides a powerful tool to test how process modifications and storage conditions affect transfused platelet function
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.10.566577
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Subjective cognitive complaints in White and African American older adults: associations with demographic, mood, cognitive, and neuroimaging features.

    Goldstein, Felicia C / Okafor, Maureen / Yang, Zhiyi / Thomas, Tiffany / Saleh, Sabria / Hajjar, Ihab

    Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition

    2023  Volume 30, Issue 6, Page(s) 957–970

    Abstract: Subjective cognitive complaints (SCC) in cognitively intact older adults have been investigated as a clinically important symptom that may portend the onset of a neurodegenerative disorder such as Alzheimer's disease. Few studies have concurrently ... ...

    Abstract Subjective cognitive complaints (SCC) in cognitively intact older adults have been investigated as a clinically important symptom that may portend the onset of a neurodegenerative disorder such as Alzheimer's disease. Few studies have concurrently incorporated demographic features, depressive symptoms, neuropsychological status, and neuroimaging correlates of SCC and evaluated whether these differ in White and African American older adults. In the current study, 131 (77 White, 54 African American) healthy participants ≥50 years old completed the Cognitive Function Instrument (CFI) to assess SCC, and they underwent objective cognitive testing, assessment of mood, and brain magnetic resonance imaging. Pearson Product Moment correlations were performed to evaluate associations of the CFI self-ratings with the above measures for the combined group and separately for White and African American participants. SCC were associated with greater depressive symptoms in both White and African American participants in adjusted models controlling for overall cognitive status, education, and hypertension. Greater white matter hyperintensities, lower cortical thickness, older age, and slower set shifting speed were associated with increased SCC in White participants. Although the correlations were not significant for African Americans, the strength of the associations were comparable to White participants. Hippocampal volume was not associated with either total SCC or items specific to memory functioning in the entire group. Longitudinal studies are needed to further evaluate the clinical significance of these associations with risk of conversion to mild cognitive impairment and dementia.
    MeSH term(s) Aged ; Humans ; Black or African American ; Cognition ; Cognitive Dysfunction/diagnosis ; Demography ; Neuroimaging ; Neuropsychological Tests ; White ; Middle Aged
    Language English
    Publishing date 2023-08-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1482447-4
    ISSN 1744-4128 ; 1382-5585
    ISSN (online) 1744-4128
    ISSN 1382-5585
    DOI 10.1080/13825585.2023.2249181
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Association of free-living diet composition with plasma lipoprotein(a) levels in healthy adults.

    Matveyenko, Anastasiya / Seid, Heather / Kim, Kyungyeon / Ramakrishnan, Rajasekhar / Thomas, Tiffany / Matienzo, Nelsa / Reyes-Soffer, Gissette

    Lipids in health and disease

    2023  Volume 22, Issue 1, Page(s) 144

    Abstract: Background: Lipoprotein (a) [Lp(a)] is an apoB100-containing lipoprotein with high levels being positively associated with atherosclerotic cardiovascular disease. Lp(a) levels are genetically determined. However, previous studies report a negative ... ...

    Abstract Background: Lipoprotein (a) [Lp(a)] is an apoB100-containing lipoprotein with high levels being positively associated with atherosclerotic cardiovascular disease. Lp(a) levels are genetically determined. However, previous studies report a negative association between Lp(a) and saturated fatty acid intake. Currently, apoB100 lowering therapies are used to lower Lp(a) levels, and apheresis therapy is FDA approved for patients with extreme elevations of Lp(a). The current study analyzed the association of free-living diet components with plasma Lp(a) levels.
    Methods: Dietary composition data was collected during screening visits for enrollment in previously completed lipid and lipoprotein metabolism studies at Columbia University Irving Medical Center via a standardized protocol by registered dietitians using 24 hour recalls. Data were analyzed with the Nutrition Data System for Research (Version 2018). Diet quality was calculated using the Healthy Eating Index (HEI) score. Fasting plasma Lp(a) levels were measured via an isoform-independent ELISA and apo(a) isoforms were measured using gel electrophoresis.
    Results: We enrolled 28 subjects [Black (n = 18); Hispanic (n = 7); White (n = 3)]. The mean age was 48.3 ± 12.5 years with 17 males. Median level of Lp(a) was 79.9 nmol/L (34.4-146.0) and it was negatively associated with absolute (grams/day) and relative (percent of total calories) intake of dietary saturated fatty acids (SFA) (R = -0.43, P = 0.02, SFA …(% CAL): R = -0.38, P = 0.04), palmitic acid intake (R = -0.38, P = 0.05), and stearic acid intake (R = -0.40, P = 0.03). Analyses of associations with HEI score when stratified based on Lp(a) levels > or ≤ 100 nmol/L revealed no significant associations with any of the constituent factors.
    Conclusions: Using 24 hour recall, we confirm previous findings that Lp(a) levels are negatively associated with dietary saturated fatty acid intake. Additionally, Lp(a) levels are not related to diet quality, as assessed by the HEI score. The mechanisms underlying the relationship of SFA with Lp(a) require further investigation.
    MeSH term(s) Male ; Humans ; Adult ; Middle Aged ; Diet ; Lipoprotein(a) ; Apolipoproteins A ; Fasting ; Energy Intake
    Chemical Substances Lipoprotein(a) ; Apolipoproteins A
    Language English
    Publishing date 2023-09-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2091381-3
    ISSN 1476-511X ; 1476-511X
    ISSN (online) 1476-511X
    ISSN 1476-511X
    DOI 10.1186/s12944-023-01884-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Relationship of apolipoprotein(a) isoform size with clearance and production of lipoprotein(a) in a diverse cohort.

    Matveyenko, Anastasiya / Matienzo, Nelsa / Ginsberg, Henry / Nandakumar, Renu / Seid, Heather / Ramakrishnan, Rajasekhar / Holleran, Steve / Thomas, Tiffany / Reyes-Soffer, Gissette

    Journal of lipid research

    2023  Volume 64, Issue 3, Page(s) 100336

    Abstract: Lipoprotein(a) [Lp(a)] has two main proteins, apoB100 and apo(a). High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease. Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined ... ...

    Abstract Lipoprotein(a) [Lp(a)] has two main proteins, apoB100 and apo(a). High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease. Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined by the number of Kringle IV Type 2 repeats. Previous studies report a strong inverse relationship between Lp(a) levels and apo(a) isoform sizes. The roles of Lp(a) production and fractional clearance and how ancestry affects this relationship remain incompletely defined. We therefore examined the relationships of apo(a) size with Lp(a) levels and both apo(a) fractional clearance rates (FCR) and production rates (PR) in 32 individuals not on lipid-lowering treatment. We determined plasma Lp(a) levels and apo(a) isoform sizes, and used the relative expression of the two isoforms to calculate a "weighted isoform size" (wIS). Stable isotope studies were performed, using D3-leucine, to determine the apo(a) FCR and PR. As expected, plasma Lp(a) concentrations were inversely correlated with wIS (R
    MeSH term(s) Humans ; Lipoprotein(a) ; Apoprotein(a)/metabolism ; Apolipoproteins A ; Atherosclerosis ; Protein Isoforms
    Chemical Substances Lipoprotein(a) ; Apoprotein(a) (EC 3.4.21.-) ; Apolipoproteins A ; Protein Isoforms
    Language English
    Publishing date 2023-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    DOI 10.1016/j.jlr.2023.100336
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Stable Isotope Tracers for Metabolic Pathway Analysis.

    Violante, Sara / Berisa, Mirela / Thomas, Tiffany H / Cross, Justin R

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 1978, Page(s) 269–283

    Abstract: Stable isotope tracing allows a metabolic substrate to be followed through downstream biochemical reactions, thereby providing unparalleled insights into the metabolic wiring of cells. This approach stops short of modeling absolute fluxes but is ... ...

    Abstract Stable isotope tracing allows a metabolic substrate to be followed through downstream biochemical reactions, thereby providing unparalleled insights into the metabolic wiring of cells. This approach stops short of modeling absolute fluxes but is relatively straightforward and has become increasingly accessible due to the widespread adoption of high-resolution mass spectrometers. Analysis of both dynamic and steady-state labeling patterns in downstream metabolites provides valuable qualitative information as to their origin and relative rates of production. Stable isotope tracing is, therefore, a powerful way to understand the impact of genetic alterations and defined perturbations on metabolism. In this chapter, we describe a liquid chromatography-mass spectrometry (LC-MS) protocol for stable isotope tracing using
    MeSH term(s) Carbon Isotopes/chemistry ; Chromatography, Liquid/methods ; Isotope Labeling/methods ; Metabolic Networks and Pathways/genetics ; Metabolomics/methods ; Tandem Mass Spectrometry/methods
    Chemical Substances Carbon Isotopes
    Language English
    Publishing date 2019-05-22
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9236-2_17
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Contribution of Peripheral Microvascular Dysfunction to Mild Cognitive Impairment.

    Gold, Matthew E / Rogers, Steven C / Kulshreshtha, Ambar / Chen, Yuxuan / Ko, Yi-An / Cheng, Michael L / Gold, Daniel A / Vatsa, Nishant / Jain, Vardhmaan / Desai, Shivang / Moazzami, Kasra / Thomas, Tiffany / Okafor, Maureen / Goldstein, Felicia / Lah, James / Quyyumi, Arshed A / Hajjar, Ihab

    The American journal of cardiology

    2024  Volume 218, Page(s) 4–6

    MeSH term(s) Humans ; Cognitive Dysfunction
    Language English
    Publishing date 2024-03-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80014-4
    ISSN 1879-1913 ; 0002-9149
    ISSN (online) 1879-1913
    ISSN 0002-9149
    DOI 10.1016/j.amjcard.2024.02.038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: TM6SF2 Determines Both the Degree of Lipidation and the Number of VLDL Particles Secreted by the Liver.

    Reyes-Soffer, Gissette / Liu, Jing / Thomas, Tiffany / Matveyenko, Anastasiya / Seid, Heather / Ramakrishnan, Rajasekhar / Holleran, Steve / Zaghloul, Norann / Sztalryd-Woodle, Carole / Pollin, Toni / Ginsberg, Henry N

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: In 2014, exome-wide studies identified a glutamine176lysine (p.E167K) substitution in a protein of unknown function named transmembrane 6 superfamily member 2 (TM6SF2). The p.E167K variant was associated with increased hepatic fat content and reduced ... ...

    Abstract In 2014, exome-wide studies identified a glutamine176lysine (p.E167K) substitution in a protein of unknown function named transmembrane 6 superfamily member 2 (TM6SF2). The p.E167K variant was associated with increased hepatic fat content and reduced levels of plasma TG and LDL cholesterol. Over the next several years, additional studies defined the role of TM6SF2, which resides in the ER and the ER-Golgi interface, in the lipidation of nascent VLDL to generate mature, more TG-rich VLDL. Consistent results from cells and rodents indicated that the secretion of TG was reduced in the p.E167K variant or when hepatic TM6SF2 was deleted. However, data for secretion of APOB was inconsistent, either reduced or increased secretion was observed. A recent study of people homozygous for the variant demonstrated reduced in vivo secretion of large, TG-rich VLDL1 into plasma; both TG and APOB secretion were reduced. Here we present new results demonstrating increased secretion of VLDL APOB with no change in TG secretion in p.E167K homozygous individuals from the Lancaster Amish community compared to their wild-type siblings. Our in vivo kinetic tracer results are supported by in vitro experiments in HepG2 and McA cells with knock-down or Crispr-deletions of TM6SF2, respectively. We offer a model to potentially explain all of the prior data and our new results.
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.23.23291823
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Reticulocytes in donor RBC units enhance RBC alloimmunization.

    Thomas, Tiffany A / Qiu, Annie / Kim, Christopher Y / Gordy, Dominique E / Miller, Anabel / Tredicine, Maria / Dzieciatkowska, Monika / Zotti, Flavia Dei / Hod, Eldad A / Dâ Alessandro, Angelo / Zimring, James C / Spitalnik, Steven L / Hudson, Krystalyn E

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent ... ...

    Abstract Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increase RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization.
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.25.525560
    Database MEDical Literature Analysis and Retrieval System OnLINE

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