Induction of Transient Cytopenia To Analyze Hematopoiesis in Mutant Mice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3158-3158
Author(s):  
William L. Stanford ◽  
Nicole M. Anderson ◽  
Mark D. Minden ◽  
Dwayne L. Barber
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Erythropoietin Receptor ◽  
Blood Levels ◽  
Pharmacological Agents ◽  
Recovery Curves ◽  
Stress Erythropoiesis ◽  
Cell Counts ◽  
B Mice ◽  
Dose Dependent

Abstract The mouse plays an indispensable role in developing our current understanding of mammalian hematopoiesis. Most hematopoietic phenotyping assays in the mouse are non-viable techniques designed to evaluate homeostatic populations, enumerate progenitor populations, and perform functional analysis. The worldwide effort to generate mouse models of human disease and functionally annotate the mammalian genome using mouse mutagenesis (including dominant ENU screens) requires the development of robust standardized viable phenotyping tools. We have developed a phenotyping assay that induces transient cytopenias using various pharmacological agents (5-fluorouracil, phenylhydrazine, and hydroxyurea), the responses to which are monitored by tracing changes in peripheral blood levels of red blood cells, white blood cells and platelets. We have performed detailed analysis of lineage recovery kinetics, developing lineage recovery curves for various strains of mice for both males and females, which allowed us to identify appropriate testing days to identify phenodeviants. We have compared the recovery data with conventional progenitor assays and analyzed a cohort of well-studied naturally occurring and targeted hematopoietic mutants using the transient anemia assays that has yielded novel phenotypes of hemizygous mutant animals. For example, erythropoietin receptor null embryos die of severe anemia at mid-gestation; however, no defect in erythropoiesis has been reported in EpoR +/− mice. We have found that 5-fluorouracil and phenylhydrazine elicit delayed RBC recovery in EpoR +/− mice, demonstrating a critical dose-dependent role for the erythropoietin receptor in stress erythropoiesis. In addition, Stat5 has been shown to play an important role in erythropoiesis and in the regulation of steady state hematopoiesis. We have found that Stat5a/b+/− mice treated with 5-fluorouracil show altered recovery kinetics in RBC, WBC and platelets. Finally, we have adapted the transient cytopenia assay to develop a sensitized dominant ENU screen, enabling us to identify hematopoietic mutants that do not present abnormal blood cell counts in a homeostatic state. Thus, these standardized cytopenia response assays function as surrogate viable assays to analyze progenitor populations.

Dominant and Pharmacologically Sensitized ENU Mutagenesis Screens Uncover Novel Regulators of Hematopoiesis and Model Hematopoietic Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1378-1378
Author(s):  
William L. Stanford ◽  
Nicole M. Anderson ◽  
Zorana Milenkovic ◽  
Lia Zitano ◽  
Lee Adamson ◽  
...  
Keyword(s):  
Gene Function ◽  
Peripheral Blood ◽  
Human Disease ◽  
Blood Cells ◽  
White Blood Cells ◽  
Blood Levels ◽  
Enu Mutagenesis ◽  
Multiple Alleles ◽  
Cell Counts ◽  
Dominant Mutants

Abstract To generate new mouse models of human hematopoietic disease and increase our knowledge of the genetic networks that control hematopoiesis, we are performing dominant (generation 1 or G1) and pharmacologically-sensitized forward ethylnitrososurea (ENU) mutagenesis screens. Mice are phenotyped by saphenous vein peripheral blood analysis using an automated hematological analyzer. ENU is ideally suited to generating models of human disease and annotating gene function because the spectrum of mutations (point mutations generating leading to subtle amino acid substitutions, splicing errors, or premature termination) are similar to those often found in human disease. Furthermore, null mutations often do not represent the full extent of a gene’s function, requiring multiple alleles to fully define gene function. While dominant mutations can unequivocally cause some human diseases, often mutations in multiple genes interact and contribute to disease progression. Thus, we have developed sensitized screens that induce transient cytopenias using various pharmacological agents (5-fluorouracil, phenylhydrazine, and hydroxyurea) and analyzing the recovery in peripheral blood levels of red blood cells, white blood cells and platelets. This strategy enables identification of hematopoietic mutants that do not present abnormal blood cell counts in a homeostatic state. The induced cytopenia recovery assay is also being used as a secondary phenotyping assay for some of our G1 dominant mutants. The combined dominant and sensitized screens have yielded 14 heritable dominant mutants to date plus four additional mutants in hereditary testing. The array of mutations that we are analyzing are models for the following diseases: polycythemia, thrombocythemia, leukocytosis, anemia, and thrombocytopenia. I will discuss the progress of the mutagenesis screen and several ENU mutants, including a novel mutation in the protein tyrosine kinase Jak2, leading to thrombocythemia. This point mutation in the protein kinase domain will help us to dissect the recently discovered role of Jak2 in Myeloproliferative Diseases including Essential Thrombocythemia.

scholarly journals Evaluation of the hemogram of Oryctolagus cuniculus envenomus

2020 ◽  
Vol 13 (2) ◽  
pp. 266-272
Author(s):  
Obou Constantin Okou ◽  
N’guessan Emmanuel Assemian ◽  
Kouadio Bernard Allali ◽  
Guy Childeric Bingo ◽  
Allico Joseph Djaman
Keyword(s):  
Blood Cells ◽  
Oryctolagus Cuniculus ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Experimental Batch ◽  
Haematological Parameters ◽  
Rabbit Blood ◽  
Hemolysis Test ◽  
Dose Dependent

The overall objective of this study was to evaluate the hemolysing action of Naja nigricollis venom on rabbit blood. To carry out this study, three batches of three rabbits were formed with two control batches and one experimental batch. Each control lot is composed of three rabbits (males or females) while the experimental lot is composed of two males and one female. Each rabbit from the control lots was separately collected in the purple tube (EDTA) and transported to the laboratory for analysis. The rabbits from the experimental batch were also collected distinctly a few minutes after the injection of the venom of Naja nigricollis for the analysis of haematological parameters. However, before the analysis of the hematological parameters of the rabbits from the control and experimental batches, an in vitro hemolysis test of Naja nigricollis venom was performed to verify its hemolysing power. The results showed that Naja nigricollis venom has a dose-dependent in vitro hemolysing power. As for the haemogram, it revealed that the venom of Naja nigricollis has a decreasing effect on blood cells (red and white blood cells), on haemoglobin and on haematocrit, and an elevation on MGVs thus promoting anaemia.

ALLIUM SATIVUM ESSENTIAL OIL (ASEO);

2017 ◽  
Vol 24 (04) ◽  
pp. 612-616
Author(s):  
Faisal Irshad ◽  
Hina Mawani ◽  
Sana Naz
Keyword(s):  
Essential Oil ◽  
Blood Cell ◽  
Blood Cells ◽  
Allium Sativum ◽  
White Blood Cells ◽  
Albino Rats ◽  
Serum Triglycerides ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Animal House

Objectives: To determine the effects of Allium sativum essential oil (ASEO)phytotherapy on serum triglycerides, total cholesterol, HDLc, LDLc and blood cell counts inalbino rat model. Study design: Experimental study. Setting and Duration: Animal House,Sindh Agriculture University and Isra University Hyderabad from May 2014 to January 2015.Materials and Methods: 60 albino rats were divided into four groups. Controls were givenPlacebo. Experimental rat groups were given ASEO 100 mg/kg, 200 mg/kg and 300 mg/kgorally for 30 days. Cardiac puncture was performed for blood sampling. Research variableswere analyzed on Statistix 10.0 (USA). Results: Blood lipids showed significant reduction invarious blood lipid fractions. Serum LDLc exhibited with a concomitant rise in serum HDLc (p=0.0001) in high ASEO treated rats. Red blood cells, white blood cells and platelet showedsignificant improvement ASEO fed rats (p=0.001). Conclusion: Allium sativum essential oil(ASEO) phytotherapy showed a rise in HDLc and a reduction in LDLc, triglycerides and totalcholesterol with improvement in red blood cell counts.

Biochemical and haematological changes associated with short periods of work in draught oxen

1989 ◽  
Vol 48 (2) ◽  
pp. 375-384 ◽  
Author(s):  
R. Anne Pearson ◽  
R. F. Archibald
Keyword(s):  
Heart Rate ◽  
Blood Cells ◽  
Inorganic Phosphate ◽  
White Blood Cells ◽  
Blood Parameters ◽  
Blood Levels ◽  
Blood Samples ◽  
Haematological Changes ◽  
Work Done ◽  
Friesian Cattle

ABSTRACTBlood samples were taken from three Brahman × Friesian cattle while they walked for 1 h daily on a treadmill pulling 20 or 25 kg weights suspended in a cage. Heart rate and energy expenditure during work were closely correlated. The work had no significant effect on blood levels of red cells, haemoglobin, packed cell volume, total protein, albumin, glycerol, urea, Mg, Ca, Na, K and chloride. White blood cells, glucose, lactate, free fatty acids, P-hydroxybutyrate and inorganic phosphate were affected by work although the changes were shortlived and values had returned to resting levels 75 min after work finished. The changes were similar in each animal and indicated work done by draught cattle is largely at a submaximal level. Apart from lactate no blood parameters were identified that could be usefully used to compare performance.

Decrease in platelet count as an independent risk factor for symptomatic vasospasm following aneurysmal subarachnoid hemorrhage

2005 ◽  
Vol 102 (5) ◽  
pp. 882-887 ◽  
Author(s):  
Yutaka Hirashima ◽  
Hideo Hamada ◽  
Masanori Kurimoto ◽  
Hideki Origasa ◽  
Shunro Endo
Keyword(s):  
Platelet Count ◽  
Subarachnoid Hemorrhage ◽  
Blood Cells ◽  
White Blood Cells ◽  
Experimental Studies ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Cell Counts ◽  
Fisher Grade ◽  
Fine Print

Object. Increased platelet consumption is expected in patients with cerebral vasospasm, according to data from clinical and experimental studies. The authors investigated sequential changes in platelet counts in patients with subarachnoid hemorrhage (SAH) and the difference in platelet consumption between patients with and those without symptomatic vasospasm (SV). Variables related to platelet count as well as other clinical and radiological variables were analyzed as independent predictors of SV. Methods. One hundred consecutive patients who had undergone surgery within 48 hours after SAH onset were entered in the study. Clinical and radiological variables and blood cell counts, including red blood cells, white blood cells, and platelets, after SAH were retrospectively examined. Twenty of these variables were entered into univariate and multivariate analyses to determine predictors for SV. After SAH, the platelet count decreased to a minimum and then increased rapidly to levels greater than those recorded on admission. This change was specific to SAH, and platelet consumption was more severe in patients with SV than in those without. There were three independent predictors of SV: a ratio of the lowest platelet count and the admission count greater than 0.7 (odds ratio [OR] 0.322, 95% confidence interval [CI] 0.124–0.834, p = 0.0196) and a history of hypertension (OR 0.338, 95% CI 0.126–0.906, p = 0.0311) were negatively significant (that is, decreases the occurrence of SV), and a Fisher Grade 3 (OR 4.42, 95% CI 1.48–13.2, p = 0.0077) was positively significant (that is, increases the occurrence of SV). Conclusions. The association between a decrease in platelet count and the occurrence of SV indicates the important role of platelets in the pathophysiology of vasospasm following SAH.

scholarly journals Prioritizing Causal Risk Factors for Severe COVID-19: An Exhaustive Mendelian Randomization Study

2021 ◽  
Author(s):  
Yitang Sun ◽  
Jingqi Zhou ◽  
Kaixiong Ye
Keyword(s):  
Risk Factors ◽  
Fat Mass ◽  
Blood Cells ◽  
Drug Targets ◽  
Large Scale ◽  
Mendelian Randomization ◽  
White Blood Cells ◽  
Fat Free Mass ◽  
Cell Counts ◽  
Increased Risk

Abstract Identifying causal risk factors for severe coronavirus disease 2019 (COVID-19) is critical for its prevention and treatment. Many associated pre-existing conditions and biomarkers have been reported, but these observational associations suffer from confounding and reverse causation. Here, we perform a large-scale two-sample Mendelian randomization (MR) analysis to evaluate the causal roles of many traits in severe COVID-19. Our results highlight multiple body mass index (BMI)-related traits as risk-increasing: BMI (OR:1.89, 95% CI:1.51–2.37), hip circumference (OR:1.46, 1.15–1.85), and waist circumference (OR:1.82, 1.36–2.43). Our multivariable MR analysis further shows that the BMI-related effect is driven by fat mass (OR:1.63, 1.03–2.58), but not fat-free mass (OR:1.00, 0.61–1.66). Several white blood cell counts are negatively associated with severe COVID-19, including those of neutrophils (OR:0.76, 0.61–0.94), granulocytes (OR:0.75, 0.601–0.93), and myeloid white blood cells (OR:0.77, 0.62–0.96). Furthermore, some circulating proteins are associated with an increased risk of (e.g., zinc-alpha-2-glycoprotein) or protection from severe COVID-19 (e.g., interleukin-3/6 receptor subunit alpha). Our study shows that fat mass and white blood cells underlie the etiology of severe COVID-19. It also identifies risk and protective factors that could serve as drug targets and guide the effective protection of high-risk individuals.

scholarly journals Platelet Activation in End-Stage Renal Disease Is Mediated By Extracellular Nucleosomes That Originate from White Blood Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4909-4909
Author(s):  
Trung Phan ◽  
McMillan Ryan ◽  
Leonidas Skiadopoulos ◽  
Amanda Walborn ◽  
Debra Hoppensteadt ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Blood Cells ◽  
White Blood Cells ◽  
Positive Correlation ◽  
Cell Counts ◽  
Wbc Count ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Abstract Introduction Extracellular nucleosomes in plasma (PNs) are complexes of DNA and histones that are released during cell death and inflammatory responses. End-stage renal disease (ESRD) represents a complex syndrome where inflammation, endothelial dysfunction, and hemostatic aberrations contribute to the observed vascular manifestations. The purpose of this investigation is to profile PNs in patients with ESRD and to demonstrate their relevance to blood cells and platelet activation products. Methods Pre-dialysis plasma samples from patients undergoing maintenance hemodialysis (n = 90) at Loyola University outpatient dialysis unit were collected under an approved IRB protocol. Plasma samples from healthy individuals (n = 50) were purchased from a biobank as a control (George King Biomedical, Overland Park, Kansas). Complete blood count profiles, including white blood cells (WBCs), red blood cells (RBCs), and platelets were obtained from the patients' medical records. The levels of PNs in ESRD patients and healthy volunteers were measured using the Cell Death Detection ELISA PLUS assay (Roche Diagnostics, Mannheim, Germany). MP-TF levels were measured using the Zymuphen MP-TF kit (Hyphen BioMed, Neuville-sur-Oise, France). PDGF levels were measured using the Human PDGF-BB Quantikine ELISA Kit (R&D Systems, Minneapolis, Minnesota). Human PF4 levels were measured using the Zymutest PF4 ELISA Kit (Hyphen BioMed, Neuville-sur-Oise, France). All individual results were tabulated and analyzed using the statistical software GraphPad Prism 7. The Mann-Whitney test for non-parametric data was utilized in comparing ESRD to control groups. PN levels were correlated with cell counts and platelet activation factors using the non-parametric Spearman correlation. Individual cell counts were also correlated with platelet activating factors using the same method. Results In the ESRD patients, the average hematocrit was 31.7 ± 4.4 %, the average WBC count was 6.5 ± 4.0 K/uL, and the average platelet count was 179.4 ± 66.3 K/uL. The levels of PNs in the ESRD patients (15.5 ± 14.1 Arbitrary Units (AU)) were markedly higher in comparison to that of the controls (6.74 ± 13.7 AU; p < 0.0001). Similarly, MP-TF levels were significantly elevated in ESRD patients (3.00 ± 1.42 pg/mL) compared to normal (0.363 ± 0.263 pg/mL; p < 0.0001). PF4 levels were also significantly elevated in ESRD patients (95.3 ± 35.3 ng/mL) compared to normal (27.4 ± 19.8 ng/mL; p < 0.0001). While PDGF levels were higher in the ESRD group (116.0 ± 172.5 pg/mL) in comparison to the controls (82.7 ± 113.5 pg/mL), this increase was not statistically significant (p = 0.405). A positive correlation was observed between PNs and WBCs (p = 0.024; r = 0.244). PN levels did not show a correlation with RBC (p = 0.448; r = 0.083) and platelet levels (p = 0.545; r = 0.066). Furthermore, there was no correlation between PNs and MP-TF (p = 0.501; r = 0.077), PDGF (p = 0.314; r = 0.110) and PF4 (p = 0.524; r = -0.070) in the ESRD patients. However, the platelet count showed a positive correlation with PDGF (p = 0.044; r = 0.218) and MP-TF (p = 0.042; r = 0.237). Similarly, the WBC count showed a positive correlation with the platelet count (p < 0.0001; r = 0.476) and PDGF (p = 0.016; r = 0.260). Conclusion This study clearly demonstrates that extracellular nucleosomes are elevated in the plasma of patients with ESRD. The fact that the PN levels correlated with the number of circulating white blood cells suggest that the PNs originate from these cells. Since the ESRD patients exhibited platelet activation, as evident by the observed increase in PDGF, MP-TF and PF4, it is plausible that this activation is mediated by PNs originating from the WBCs. As observed by the positive correlation between WBCs, PDGF, and platelet count, this study underscores the potential role of nucleosomes originating from WBCs in the activation of platelets. These results are consistent with previously reported observations that extracellular histones can induce platelet activation in a TLR2 and TLR4 dependent manner (http://www.ncbi.nlm.nih.gov/pubmed/21673343). Disclosures No relevant conflicts of interest to declare.

scholarly journals Serum Bilirubin level and its correlation with white blood cells as risk factor for cardiovascular disease in adult healthy population.

2020 ◽  
Vol 27 (12) ◽  
pp. 2622-2627
Author(s):  
Kashif Rasheed Shaikh ◽  
Shumaila Shaikh ◽  
Shagufta Memon ◽  
Umair Ali Soomro ◽  
Shumail Saeed Siddiqui ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Blood Glucose ◽  
Blood Cells ◽  
Healthy Subjects ◽  
Serum Bilirubin ◽  
White Blood Cells ◽  
Serum Total Bilirubin ◽  
Healthy Population ◽  
Cell Counts

Objectives: Evaluate serum bilirubin in adult healthy subjects and its correlation with white blood cells as risk factor for cardiovascular disease. Study Design: Cross- sectional study. Setting: Department of Pharmacology and Medicine, Suleman Roshan Medical College. Period: January - December 2017. Material & Methods: A sample of 100 male and 100 female adult healthy subjects were recruited for study protocol. Blood glucose, Serum creatinine, Blood lipids, liver enzyme levels, White blood cell counts and Serum bilirubin levels were analyzed. Pearson`s correlation was used for the correlation coefficient and its statistical significance for the association of serum bilirubin and white blood cells. Data variables were analyzed by statistical software SPSS (ver 21.0) at 95% CI (P ≤ 0.05). Results: Mean± SD age of male and female was found 47.02±8.42 and 48.59±7.80 years respectively (P=0.071). Serum bilirubin shows statistically significant negative correlation with blood glucose (r= - 0.257, P=0.0001) and LDLc (r= - 0.155, P=0.027) and WBC (r= - 0.871, P=0.0001). Conclusion: The present study shows the elevated serum total bilirubin levels within reference range correlated negatively with total white blood cells in adult healthy population.

scholarly journals Moderate Range Static Magnetic Field Promoted Variation of Blood Parameters: An In vitro Study

2020 ◽  
Vol 8 (1) ◽  
pp. 55-64
Author(s):  
Bestoon T. Mustafa ◽  
Sardar P. Yaba ◽  
Asaad H. Ismail
Keyword(s):  
Magnetic Field ◽  
Blood Cell ◽  
Static Magnetic Field ◽  
Blood Cells ◽  
White Blood Cells ◽  
Albino Rats ◽  
Field Exposure ◽  
Blood Samples ◽  
Cell Counts

This study was undertaken to investigate the influence of a homogenous and uniform static magnetic field (SMF) on the main blood cell counts in vitro experiment. Fresh blood samples were collected from albino rats and exposed to SMF (2.4, 6, 25, 50, 75, and 100 mT) versus 15–60 min. Results showed a significant change of blood counts under the low field effects. A 2.4 mT was a trend of white blood cells (WBCs) count increase non-linearly. However, a 6 mT exposure reduced WBCs with about 39%. Other variations fluctuated within 30%. The 25 mT decreased red blood cells (RBCs), hemoglobin, and hematocrit levels with 13% similarly. The lower exposure field, (2.4 and 6) mT, and effects on RBCs were 6% fluctuation. The 6 mT reduced platelet counts with half in comparison to control blood samples. About 20% increase obtained due to 50 mT exposure during all period. None of 75 and 100 mT exposures dominated blood counts alterations. The quiet magnetic field exposure for a certain time can be interesting to control blood cell count-related diseases.

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