scholarly journals Systems-level physiology of the human red blood cell is computed from metabolic and macromolecular mechanisms

2019 ◽  
Author(s):  
James T. Yurkovich ◽  
Laurence Yang ◽  
Bernhard O. Palsson

ABSTRACTThe human red blood cell has served as a starting point for the application and development of systems biology approaches due to its simplicity, intrinsic experimental accessibility, and importance in human health applications. Here, we present a multi-scale computational model of the human red blood cell that accounts for the full metabolic network, key proteins (>95% of proteome mass fraction), and several macromolecular mechanisms. Proteomics data are used to place quantitative constraints on individual protein complexes that catalyze metabolic reactions, as well as a total proteome capacity constraint. We explicitly describe molecular mechanisms—such as hemoglobin binding and the formation and detoxification of reactive oxygen species—and takes standard hematological variables (e.g., hematocrit, hemoglobin concentration) as input, allowing for personalized physiological predictions. This model is built from first principles and allows for direct computation of physiologically meaningful quantities such as the oxygen dissociation curve and an accurate computation of the flux state of the metabolic network. More broadly, this work represents an important step toward including the proteome and its function in whole-cell models of human cells.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4888-4888
Author(s):  
James T Yurkovich ◽  
Laurence Yang ◽  
Bernhard O Palsson

Abstract The human red blood cell has served as a starting point for the application and development of systems biology approaches due to its simplicity, intrinsic experimental accessibility, and importance in human health applications. Here, we present a multi-scale computational model of the human red blood cell that accounts for metabolism and macromolecules. Proteomics data are used to place quantitative constraints on individual protein complexes that catalyze metabolic reactions, as well as a total proteome capacity constraint. We explicitly describe molecular mechanisms-such as hemoglobin binding and the formation and detoxification of reactive oxygen species-and account for sequence variations between individuals, allowing for personalized physiological predictions. This model allows for direct computation of the oxyhemoglobin curve as a function of model species and a more accurate computation of the flux state of the metabolic network. More broadly, this work represents another step toward building increasingly more complete systems biology whole-cell models. Disclosures No relevant conflicts of interest to declare.



1985 ◽  
Vol 24 (9) ◽  
pp. 1355 ◽  
Author(s):  
D. H. Tycko ◽  
M. H. Metz ◽  
E. A. Epstein ◽  
A. Grinbaum


2021 ◽  
Vol 12 ◽  
Author(s):  
Chongjun Wu ◽  
Ting Xiong ◽  
Zhongjin Xu ◽  
Chunlei Zhan ◽  
Feng Chen ◽  
...  

ObjectiveTo investigate the clinical and genetic characteristics of hereditary spherocythemia (HS) in Chinese children, and to analyze the potential genotypic/phenotypic associations.MethodsThe clinical data and gene test results of children with HS were collected. All patients were diagnosed by gene test results, and the laboratory results were obtained before splenectomy. The data of red blood cell (RBC), hemoglobin (HB), mean red blood cell volume (MCV), mean red blood cell hemoglobin (MCH), mean red blood cell hemoglobin concentration (MCHC), and hematocrit (HCT) were statistically analyzed according to different mutation genes. Statistical methods for comparison between groups Mann–Whitney test analysis, two-terminal p < 0.05 was considered significant difference.ResultsA total of 15 children were enrolled in our hospital, and 14 variants were found (nine variants have not been reported before), including 10 ANK1 mutations (seven ANK1 truncated mutations) and five SPTB mutations. Patients with ANK1 mutations had more severe anemia than those with SPTB mutations (significantly lower RBC, HB, MCHC, and HCT).ConclusionThis is one of the few studies on the genetic and clinical characteristics of children with HS in China. This study identified the unique genetic and clinical characteristics of Chinese children with HS and analyzed the pathogenic genotype–phenotypic association. The results confirmed that the anemia degree of HS patients caused by ANK1 was more serious than that of patients with SPTB deficiency. However, further study of the correlation between genotype and phenotype requires a larger sample size.



Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Arvand Barghi ◽  
Robert Balshaw ◽  
Emily Rimmer ◽  
Murdoch Leeies ◽  
Allan Garland ◽  
...  

Background: Red blood cell (RBC) transfusions are often used to treat patients with iron deficiency who present to the emergency department (ED) with symptomatic anemia. Intravenous (IV) iron is the preferred treatment in this setting, as it has been shown to increase hemoglobin concentration rapidly and durably. We aim to determine the incidence of iron deficiency anemia (IDA) and the management of these patients in the ED setting. Objectives: To evaluate the incidence of IDA, the frequency of RBC transfusion and iron supplementation, and factors associated with RBC transfusion. Study Design: Retrospective cohort study of all adult patients presenting to the St Boniface Hospital (Winnipeg, CAN) ED from January 2014 to January 2019. Methods: We used electronic data from the Emergency Department Information System (EDIS) and Laboratory Information Services (LIS) databases to identify patients presenting with IDA, defined as anemia (hemoglobin <120 g/L) with either a transferrin saturation less than 20% or ferritin less than 30 umol/L, or mean corpuscular volume (MCV) of < 75 fL. A ferritin greater than 100 umol was used to exclude IDA, regardless of MCV. We extracted patient demographics, diagnoses, markers of iron storage, RBC transfusion and use of IV iron. Multivariate logistic regression analysis was used to evaluate factors associated with RBC transfusion. Results: Of 39222 patients, 17945 (45%) were anemic. Of the anemic patients, iron parameters were ordered in 1848 (10.3%) patients, and IDA was present in 910 (5.1 %). In the IDA population, 95 patients (10.4 %) received 1 RBC unit, and 197 patients (21.6 %) received 2 or more units. Oral iron and IV iron were prescribed for 64 (7 %) and 14 (1.5 %) patients, respectively. Our logistic regression model demonstrated that hemoglobin concentration was the main determinant of whether patients received RBC transfusion. Other variables including patient age, cardiac symptoms, heart rate, blood pressure, and CTAS score were not associated with increased likelihood of receiving RBC transfusion. Conclusion: Iron parameters were infrequently ordered in the evaluation of anemia in the ED, with limited use of oral and IV iron. The decision to transfuse RBCs was primarily influenced by hemoglobin concentration, but not other surrogates of hemodynamic instability. An interventional study to improve education and access to oral and IV iron is planned to reduce unnecessary RBC transfusions and their associated risks in patients with IDA. Disclosures No relevant conflicts of interest to declare.



Author(s):  
Jasmina PLUNCEVIC GLIGOROSKA ◽  
Serjoza GONTAREV ◽  
Beti DEJANOVA ◽  
Lidija TODOROVSKA ◽  
Daniela SHUKOVA STOJMANOVA ◽  
...  

Background: This study aimed to assess the basic red blood cell variables and hematological indices in children and adolescents and analyze the differences regarding age and sex. Methods: Overall, 320 young participants, age 8 to 18 yr, were enrolled at Laboratory of Sport’s Medicine, Medical Faculty, Skopje, Macedonia in 2016. Capillary blood samples were drawn and following hematologic parameters were measured: the red blood cell count (RBC), hemoglobin concentration (Hb), hematocrit level (Hct) and hematological indexes: mean corpuscular volume (MCV), mean hemoglobin concentration (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW). Results: RBC variables in male group showed high statistical level of significance between age different groups (P=0.001) for all studied parameters except MCHC (P=0.423) and RDW (P=0.174). ANOVA test and multivariate tests in female group showed that there was no significant difference for all hematological parameters between age different groups. Regarding the sex differences, male participants had significantly higher red blood count (P<0.001), hemoglobin content (P<0.001) and hematocrit (P<0.001). Conclusion: Hematological parameters in adolescent as inhomogeneous population are not quantified sufficiently, especially hematological indices. RBC variables, regardless of the age, differ very much between male and female examinees, in favor of the male examinees. Hematological indices were insignificantly higher in males. Regarding the age of examinees, RBC variables showed significant inter-groups differences only within male adolescents. While with girls, ages span 8 to 18 yr, we did not find significant differences for most of the hematological variables.



2019 ◽  
Vol 70 (1) ◽  
pp. 69-80
Author(s):  
Guang Cai ◽  
Jun Qiu ◽  
Shuai Chen ◽  
Qile Pan ◽  
Xunzhang Shen ◽  
...  

Abstract This study objective was to evaluate gender differences in hematological, hormonal and fitness variables among youth swimmers and to explore relationships between erythrocyte indices and aerobic and anaerobic capacity. 137 girls and 171 boys participated in the study and were divided into three groups based on their training experience. Blood samples were obtained to determine red blood cell counts, hemoglobin concentration, hematocrit, and plasma erythropoietin and testosterone levels. VO2max was assessed using a submaximal cycle protocol. 76 girls and 102 boys also undertook a Wingate test to determine their peak anaerobic power. Boys had higher (p < 0.05) means than girls for all hematological variables except for erythropoietin and these variables demonstrated an increase with training in boys. The average VO2max in l∙min-1 and peak anaerobic power in watts were also higher in boys (2.91 ± 0.08 and 547 ± 28, respectively) than girls (2.25 ± 0.07 and 450 ± 26, respectively). Modest but significant (p < 0.05) correlations were found between VO2max and red blood cell counts (r = 0.252), hemoglobin concentration (r = 0.345), or hematocrit (r = 0.345) and between peak anaerobic power and red blood cell counts (r = 0.304), hemoglobin concentration (r = 0.319) or hematocrit (r = 0.351). This study revealed relatively lower yet age- and gender-appropriate hematological, hormonal and fitness indices in youth swimmers. The gender-related differences in erythrocyte indices seem unrelated to erythropoietin and may be explained by the higher testosterone levels seen in boys. Given their correlation to both aerobic and anaerobic capacity, erythrocyte indices may be used as part of talent identification for sports.



Author(s):  
Georges Aoun ◽  
Pamela Aoun ◽  
Abbass El-Outa

Anemia is a condition of decreased red blood cell number or hemoglobin concentration, or of disturbance in their function, ultimately leading to decreased oxygen transport to tissues. Many factors and diseases may lead to anemia, with wide manifestations systemically as well as orally. Therefore, a sound understanding of this syndrome is essential for the dental practitioner, with emphasis on alerting signs, dental management and proper communication with patient&rsquo;s physician.



Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 818-823 ◽  
Author(s):  
G d'Onofrio ◽  
R Chirillo ◽  
G Zini ◽  
G Caenaro ◽  
M Tommasi ◽  
...  

Using the new Bayer H*3 hematology analyzer (Leverkusen, Germany), we have determined red blood cell and reticulocyte indices in 64 healthy subjects, in patients with microcytosis due to iron deficiency (58 patients) and heterozygous beta-thalassemia (40 patients), and in patients with macrocytosis (28 patients). We found in all cases that reticulocytes were larger than mature red cells by 24% to 35%, with a hemoglobin concentration 16% to 25% lower and a similar hemoglobin content. The correlation between red cell and reticulocyte indices was strikingly tight (r = .928 for volume, r = .929 for hemoglobin concentration, r = .972 for hemoglobin content) in all four groups, regardless of red blood cell size. The ratio of reticulocyte to red blood cell mean corpuscolar volume (MCV ratio) was constantly above 1. Inversion of the MCV ratio was observed only in four patients. It was always abrupt and transitory and was associated with erythropoietic changes leading to the production of red blood cells of a different volume (treatment of megaloblastic anemia, functional iron deficiency, bone marrow transplantation). In two cases of marrow transplantation, reticulocyte volume fell during the aplastic phase after conditioning chemotherapy and then rapidly increased up to values higher than before; this production of macroreticulocytes was the earliest sign of engraftment.



2019 ◽  
Vol 9 (22) ◽  
pp. 4827 ◽  
Author(s):  
Joames K. Freitas Leal ◽  
Dan Lazari ◽  
Coen C.W.G. Bongers ◽  
Maria T.E. Hopman ◽  
Roland Brock ◽  
...  

Our knowledge on the molecular mechanisms of red blood cell aging is mostly derived from in vitro studies. The Four Days Marches of Nijmegen in the Netherlands, the world’s largest yearly walking event, constitutes a unique possibility to study the effect of mechanical and biochemical stressors occurring during moderate-intensity exercise on red blood cell aging in vivo. Therefore, longitudinal measurements were performed of biophysical, immunological, and functional red blood cell characteristics that are known to change during aging. Our data show that moderate-intensity exercise induces the generation of a functionally improved red blood cell population with a higher deformability and a decreased tendency to aggregate. This is likely to be associated with an early removal of the oldest red blood cells from the circulation, as deduced from the (dis)appearance of removal signals. Thus, the physiological red blood cell aging process maintains homeostasis in times of moderate-intensity exercise-induced stress, probably by accelerated aging and subsequent removal of the oldest, most vulnerable red blood cells.



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