scholarly journals Duffy Antigen Phenotyping Is a Useful and Clinically Available Test for Benign Ethnic Neutropenia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2546-2546 ◽  
Author(s):  
Eric Y. Chang ◽  
Christopher A. Tormey ◽  
Alexa J. Siddon ◽  
Mahboubeh Rahmani ◽  
Ellice Y. Wong
Keyword(s):  
African American ◽  
Blood Cell ◽  
Ethnic Groups ◽  
Neutrophil Count ◽  
African Ancestry ◽  
Clinical Suspicion ◽  
Control Group ◽  
Hematologic Disorders ◽  
Duffy Antigen ◽  
The Mean

Abstract Introduction: Benign Ethnic Neutropenia (BEN) is the most common form of neutropenia worldwide and is usually defined as a neutrophil count under 1.5x103/uL without increased infection risk. BEN has been observed predominantly in individuals of African ancestry as well as in certain Middle Eastern ethnic groups. The discovery of neutropenia during routine laboratory testing, however, may prompt extensive workup for infectious, autoimmune, and hematologic disorders. Identifying a readily available test to diagnose BEN in the appropriate ethnic and clinical setting could preempt unnecessary and invasive testing such as a bone marrow aspiration and biopsy and minimize patient anxiety. The absence of the red blood cell (RBC) Duffy antigen, Fy (a- b-), is thought to be responsible for BEN. As the Duffy antigen is utilized by the parasite Plasmodium vivax to enter the RBC, it has been hypothesized that in West Africa, positive selection for the null allele enabled individuals to be protected against infection and have a survival advantage. Aim: Our study examined whether testing for the Fy phenotype could reliably be used as a clinical assay to identify patients with BEN. Methods: Our cases included patients at the VA CT Healthcare System clinically diagnosed with BEN and controls that were chosen randomly from the pools of patients for whom a CBC and type and screen were checked for any other reason. Both probable BEN cases and controls were tested for the Fy phenotype using standard serologic methods in the blood bank. The Fy phenotype, absolute neutrophil count (ANC), white blood cell count (WBC), hemoglobin level, platelet count, and medical diagnoses were extracted from the medical record. Applicable data were compared statistically using the Mann-Whitney U Test with significance set at p < 0.05. Results: Our study included 32 patients (mean age 54, range 21 to 90) who were clinically identified as probable BEN cases and 50 patients (mean age 68, range 38 to 97) chosen as controls. In the probable BEN group, 28 patients self-identified as African American or Black and 3 declined self-identification. In the control group, 11 patients self-identified as African American or Black, 34 self-identified as White, 2 self-identified as Hispanic, 2 declined self-identification, and 1 self-identified as Native Hawaiian. The majority of probable BEN patients (31 of 32) and only a minority of control patients (6 of 50) were Fy (a- b-). Most study patients were male: 30 of 32 probable BEN patients and all control patients were male. The mean ANC count for Fy(a- b-) probable BEN patients was significantly lower than controls (1.68x103/uL versus 5.46x103/uL, p < 0.0001). Similarly, the mean WBC count for Fy (a- b-) probable BEN patients was significantly lower than the mean WBC for controls (3.72 x 103/uL versus 8.14 x 103/uL, p < 0.0001). Hemoglobin was comparable between Fy(a- b-) probable BEN patients and controls (12.91 g/dL versus 11.68 g/dL, p = 0.0673) as were platelets between Fy(a- b-) probable BEN patients and controls (194x103/uL versus 213x103/uL, p = 0.4354). The only African American patient presumed to have BEN that was not confirmed by Fy testing was found to have concurrent diagnoses that could otherwise explain his neutropenia (HIV/HCV). The remaining confirmed BEN cases did not have an accompanying marrow suppressive hematologic disorder. Five control group patients had potentially marrow suppressive hematologic disorders including myelodysplastic syndrome and acute myeloid leukemia. Conclusions: Readily available serologic testing in the blood bank for Duffy antigen phenotyping can be used to confirm suspected BEN in patients with high clinical suspicion. Further testing is in progress of Fy phenotyping comparing controls with neutropenia for any reason to our proposed BEN population to better determine the positive predictive value. Fy phenotyping to confirm BEN suspicion may help avoid unnecessary and invasive neutropenia testing. In addition, since BEN affects certain ethnic groups (primarily those of African ancestry), these individuals may be unfairly excluded from possible treatment including cytopenia-inducing psychiatric medications like clozapine, myelosuppressive chemotherapy, and clinical trials due to ANC eligibility requirements. Fy phenotyping to confirm clinical suspicion of BEN could be a useful tool to help develop modified guidelines for neutropenia-inducing medication. Disclosures No relevant conflicts of interest to declare.

Distinct roles of Toll-like receptor-4 expression in neonate infected by neonatal meningitis

2016 ◽  
Vol 4 (2) ◽  
pp. 150-166
Author(s):  
Jack B. Smith ◽  
Enza Hijiya
Keyword(s):  
Laboratory Testing ◽  
Clinical Suspicion ◽  
Cytokine Level ◽  
Neonatal Meningitis ◽  
Control Group ◽  
Fluorescence Index ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
The Mean ◽  
Level Analysis

The objective of the study is to evaluate the expression of Toll-like receptor-4 (TLR-4) in neonate infected by neonatal meningitis. Thirty neonate under the age 30 days with the clinical suspicion of neonatal meningitis were enrolled in the study. CSF and Nasopharyngeal secretions were obtained for laboratory testing, and blood samples were obtained for flow cytometry and cytokine level analysis. The mean fluorescence index, used as a measure of TLR-4 expression by monocytes, was significantly higher with neonatal meningitis than in the control group neonate (51.26 ± 29.41 vs. 28.22 ± 12, respectively; P= 0.002). We concluded that TL4 expression by monocytes are higher in neonate with positive PCR results for neonatal meningitis.

Common VWF Haplotypes in Normal African-Americans and Caucasians Recruited into the ZPMCB-VWD and Their Impact on VWF Laboratory Testing.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 714-714
Author(s):  
Veronica H. Flood ◽  
B.C. Kautza ◽  
C.A. Miller ◽  
B.R. Branchford ◽  
J.C. Gill ◽  
...  
Keyword(s):  
African American ◽  
African Americans ◽  
Gene Sequencing ◽  
Von Willebrand Disease ◽  
Control Group ◽  
Healthy Controls ◽  
Significant Difference ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Von Willebrand disease (VWD) is a common bleeding disorder that has been reported to affect up to 1% of the population. Diagnostic testing for VWD relies on specific tests of von Willebrand factor (VWF) that include VWF antigen (Ag) and VWF ristocetin cofactor activity (RCo). Variability in these tests, especially in the RCo, has the potential to affect diagnosis of VWD. Clinically, the RCo/Ag ratio is used to identify patients with type 2M VWD, of which 35% of our local type 2M index cases were of African-American descent. As part of the ZPMCB-VWD, a large study of both healthy controls and patients with VWD, we evaluated VWF Ag, RCo, multimers, EU bleeding score, and VWF gene sequencing to look for mutations and/or common polymorphisms (SNPs) that might contribute to RCo measurement. Healthy controls completed a computerized version of the EU bleeding score and provided blood for clinical VWF testing. Since platelet VWF binding primarily involves the A1 domain of VWF, exon 28 gene sequencing was analyzed and common SNPs were identified, particularly in African-Americans (AA) with altered RCo/Ag ratios. Statistical comparisons were performed using t-tests. For the AA control group, the presence of specific exon 28 SNPs, including I1380V, N1435S, and D1472H, correlated with a low RCo/Ag. In controls, the 3 SNPs occurred together in 22% of AA and 1.5% of Caucasians. For AA controls with all 3 SNPs, the mean Ag was 155, RCo 115, and RCo/Ag 0.77, while for AA without the 3 SNPs, the mean Ag was 129, RCo 129, and RCo/Ag 1.01. The difference in RCo/Ag ratio was significant (p<0.001). In comparison, the Caucasian controls without the 3 SNPs had a mean Ag of 108, RCo of 115, and RCo/Ag of 1.08. When only D1472H was considered, a significant difference in RCo/Ag ratio was noted for both African-American and Caucasian controls with D1472H (present in 63% of AA and 24% of Caucasian controls). For AA controls with D1472H, the mean RCo/Ag ratio was 0.82 (range 0.42–1.16) compared to 1.01 for those without the SNP (p<0.001). The Caucasian controls with D1472H had a mean ratio of 0.87 (range 0.57–1.17) compared to 1.08 for those without the SNP (p<0.001). EU Bleeding Score was not significantly affected by either race or SNP status. All Caucasian controls with D1472H were heterozygous, while 14% of the African-American controls were homozygous. The mean RCo/Ag for the homozygous controls was 0.71, compared to 0.86 for the AA heterozygous controls (p<0.025). In order to determine if the exon 28 SNPs intrinsically altered the measurement of VWF, the 3 SNPs were engineered into recombinant VWF and expressed in HEK293T cells. VWF Ag and RCo were performed on the purified expressed VWF. The RCo/Ag ratios for the recombinant expressed VWF were decreased for 1380V and 1472H, while the construct containing all 3 SNPs showed an even lower ratio (59% of wild-type RCo/Ag ratio). These data suggest that specific exon 28 SNPs may contribute to low RCo/Ag ratios, especially in the African-American population. Since the RCo assay involves ristocetin binding to VWF, mutations (and polymorphisms) in VWF may affect the measurement of “VWF activity” by this assay and might not reflect true hemorrhagic risk.

Ex Vivo Expansion Reduces Neutropenia Post Autologous Transplantation of Peripheral Blood Hematopoïetic Stem Cells in Patients with Follicular Lymphoma. A Randomized, Double Blind Trial,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4009-4009
Author(s):  
Helene Trebeden-Negre ◽  
Sylvain Choquet ◽  
Michelle Rozenzwajg ◽  
Nabih Azar ◽  
Francois Lefrère ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Autologous Transplantation ◽  
Ex Vivo Expansion ◽  
Control Group ◽  
Double Blind ◽  
Cd34 Cells ◽  
The Mean

Abstract Abstract 4009 The ex vivo culture of Hematopoietic Stem Cells (HSC) with various combinations of cytokines can increase the number of mature hematopoietic cells that are theoretically capable of rapidly release neutrophils and platelet and reduce recovery duration post transplantation. In patients, the infusion of such cells has been reported, but the short-term effect was not clear. In a randomized, double blind study, we used expanded cells from 4×106/kg peripheral blood hematopoietic selected CD34+cells in comparison to a non manipulated graft containing the same number of CD34+ cells; we designed an ex vivo expansion protocol based on a cocktail of early or late acting cytokines with different culture duration in order to obtain progenitors at various stages of differentiation 1) primitive progenitors obtained from selected CD34+cells cultured for 8 days in presence of fetal liver tyrosine kinase 3 ligand (FLT3-ligand), stem cell factor (SCF), interleukin-3 (IL-3) and thrombopoietin (TPO), 50 ng/ml, each 2) committed megakaryocyte progenitors (Mks) obtained after culture for 10 days in presence of TPO et SCF (50 ng/ml, each) or 3) committed granulocytes and megakaryocyte (GMks) progenitors obtained after culture for 10 days in presence of TPO, SCF and G-CSF (100 ng/ml). Eighteen Non Hodgkin Lymphoma patients submitted to autologous transplantation after a myeloablative regimen consisting of AraC: Day (D)-6 to D-3: 200mg/m2/12h - VP16: 100mg/m2/12h: D-6 to D-3 - BCNU: 300mg/M2: D-6- Melphalan: 140mg/M2: D-2 could be evaluated. Patients in the Expansion Group received graft with 1×106/kg non manipulated cells combined with primitive progenitors issues from 2×106/kg CD34+ cells and Mks progenitors (Mks Expansion Group) or GMks progenitors (GMks Expansion Group) coming from 1×106/kg CD34+cells; unmanipulated cells were used as a source of immunocompetent cells. In the mean, patients of control group (n=10) received 1.3±0.9×108Total Nucleated Cells (TNC)/Kg, 2.7±1.2×106 CD34+/kg, 49±17×104/kg CFU-GM and 17.7±.7104CFU-Mks/kg; in the Mks (n=4) and GMks (n=4) Expansion group, they received respectively in the mean: 61.5±18.5 and 90.1±21.3×108TNC /Kg, 26.5±10.7 et 31± 11.2 x106CD34+/kg, 451± 188 et 557±216×104/kg CFU-GM, 358±212 et 39±18.1 x104/kg CFU-Mk. No cytokines were administered after transplantation. No toxicity was observed after cell infusion. The mean times to reach white blood cell (WBC) recovery (WBC >1x 109/l) was significantly shorter after administration of expanded cells, 14 (10–16), 12 (11–14) and 9 (9–10) days respectively in control, Mks and GMks Expansion Group (p=0.01). Median profound neutropenia (neutrophils<0,5×109/l) duration was 4 (4–5) days in the GMk Expansion Group versus 9 (7–11) in the Mks Expansion Group and 9 (6–14) in the control group (p<0.05); no patient demonstrated abrogation of neutropenia. In contrast, ex vivo expansion did not reduce the time to platelet recovery (>25 or50×109/L) despite numerous mature megakaryocytes and CFU-Mks in the Mks Expansion Group; that could be related to the colonies size, very small from expanded cells. No secondary hypoplasia was observed during the 12 months follow-up. This study shows that in comparison with unmanipulated cells, peripheral blood haematopoietic cells expanded from similar doses of CD34+ cells accelerate neutrophil recovery without impairing long-term haematopoiesis and open interesting perspectives in the field of allogeneic cord blood cell transplantation. Disclosures: Leblond: Roche, Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees.

PSII-14 Supplementation of Bacillus Amyloquefaciens on Systemic Immunity of Weaned Pigs Experimentally Infected with a Pathogenic E. coli

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 168-169
Author(s):  
Cynthia Jinno ◽  
Braden T Wong ◽  
Martina Kluenemann ◽  
Xunde Li ◽  
Yanhong Liu
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
Neutrophil Count ◽  
Complete Blood Count ◽  
Control Group ◽  
Blood Cell Count ◽  
Weaned Pigs ◽  
E Coli ◽  
Antibiotic Group ◽  
Wbc Count

Abstract The objective of this experiment was to investigate the effects of dietary supplementation of Bacillus amyloquefaciens on total and differential blood cell count in weaned pigs experimentally infected with a pathogenic E. coli. A total of 50 weaned pigs (7.41 ± 1.35 kg) were individually housed in disease containment rooms and randomly assigned to one of the 5 treatments: sham control (CON-), sham B. amyloquefaciens (BAM-), challenged control (CON+), challenged B. amyloquefaciens (BAM+) and challenged carbadox (CAR+). The experiment lasted 28 days with 7 days’ adaptation and 21 days after the first E. coli inoculation. The doses of F18 E. coli inoculum were 1010 CFU/3 mL oral dose daily for 3 consecutive days. Whole blood samples were collected from all pigs on d -7, and d 0, 7, 14, and 21 post infection (PI) to measure total and differential blood cell count by complete blood count (CBC) analysis. Supplementation of BAM or CAR increased (P &lt; 0.05) either the percentage or the number of lymphocytes on d 0 before E. coli inoculation. E. coli challenge increased (P &lt; 0.05) white blood cell (WBC) count on d 7 and 21 PI, while supplementation of BAM tended (P &lt; 0.10) to have low WBC on d 7 PI and had lower (P &lt; 0.05) WBC on d 21 PI compared with CON+. Pigs in BAM+ also had lower (P &lt; 0.05) neutrophil count on d 14 PI, pigs fed with CAR had lower (P &lt; 0.05) neutrophil count on d 14 and 21 PI, compared with pigs in CON+. No difference was observed in red blood cell profile among all treatments throughout the experiment. In conclusion, pigs fed with B. amyloquefaciens have similar systemic immune response to pigs in antibiotic group and have relatively lower systemic inflammation caused by E. coli compared with control group.

scholarly journals Transcriptome-Wide Association Study of Blood Cell Traits in African Ancestry and Hispanic/Latino Populations

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1049
Author(s):  
Jia Wen ◽  
Munan Xie ◽  
Bryce Rowland ◽  
Jonathan D. Rosen ◽  
Quan Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
African American ◽  
Blood Cell ◽  
Association Study ◽  
Target Genes ◽  
Prediction Models ◽  
African Ancestry ◽  
Reference Panel ◽  
European Ancestry ◽  
Hematological Trait

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Moreover, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including n = 229 African American and n = 381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, n = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (n = 27,955) and Hispanic/Latino (n = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p < 1 × 10−4) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (n = 802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

scholarly journals The relationship between some biochemical and hematological changes in type 2 diabetes mellitus

2017 ◽  
Vol 4 (11) ◽  
pp. 1760
Author(s):  
Zafer Saad Al Shehri
Keyword(s):  
Diabetes Mellitus ◽  
Blood Cell ◽  
Cell Count ◽  
Control Group ◽  
Blood Cell Count ◽  
Distribution Width ◽  
Mean Values ◽  
Lymphocyte Ratio ◽  
The Mean

Introduction: The aim of this study was to investigate various biochemical and hematological parameters in patients with type 2 diabetes mellitus (T2DM) and compare those with non-diabetic subjects (control group). Subjects: The study was conducted on 405 subjects (ages ranging from 26-65 years old; sex matched) who were classified into two groups: diabetic (n=205 subjects; males-105, females-100) and non-diabetic  subjects (n=200; males-100, females-100). The study was carried out during the period of November 2016 to April 2017 in the Department of Clinical Laboratory Sciences at the College of Applied Medical Science Al-Dawadmi, Shaqra University in Saudi Arabia (with the collaboration of the General Hospital Al-Dawadmi). Methods: The following various parameters were assessed for all subjects: body mass index (BMI), systolic and diastolic blood pressure (SBP-DBP), fasting blood sugar (FBS), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatise (ALP), total cholesterol (T. Ch), triglyceride (TG), low-density lipoprotein (LDL), high density lipoprotein (HDL), hemoglobin (HB), red blood cell count (RBC), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscle hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), red cell distribution width (RDW), platelet count (Plt), mean platelet volume (MPV), platelet distribution width (PDW), total white blood cell count (WBC), lymphocyte count (L), neutrophil count (N),  eosinophil count (E), monocyte count (M), basophil count (B), neutrophil/lymphocyte ratio (N/L), and platelet/lymphocyte ratio (P/L). Results: The results showed an increase in the mean values of SGPT, alkaline phosphatase, urea, serum creatinine, total cholesterol, triglyceride, and LDL in the T2DM group relative to the control group. Meanwhile, the mean value of HDL was significantly decreased in the T2DM group compared to the control group (p<0.05). The mean values of hemoglobin, RBC, MCV, MCHC and MCH were significantly decreased in the T2DM group compared to the control group. In contrast, the red cell distribution width significantly increased in the T2DM group versus control group (p<0.05). The mean platelet count was not significantly changed in the T2DM group compared to the control group (p> 0.05), but the mean values of PDW and MPV were significantly higher in the T2DM group compared to the control group (p<0.05). The mean white blood cell count and differential white blood cell was significantly higher in the T2DM group compared to control group (p<0.05). Lastly, the mean neutrophil/lymphocyte ratio and platelet/lymphocyte ratio was not significantly different in the T2DM group compared to control group (p>0.05). Conclusion: In diabetes mellitus type 2 patients, certain biochemical and hematological changes are distinct from healthy subjects. It is important to follow up and monitor these parameters carefully in diabetic patients. Peer Review Details Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy Plagiarism software screening?: Yes Date of Original Submission: 30 September 2017 Date accepted: 05 November 2017 Peer reviewers approved by: Dr. Lili Hami Editor who approved publication: Dr. Phuc Van Pham  

scholarly journals Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, Mean Platelet Volume and Red Cell Distribution Width Measures in Bells Palsy

2017 ◽  
Vol 5 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Caner Sahin ◽  
Ceyhun Varım
Keyword(s):  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Control Group ◽  
Red Cell ◽  
Cell Distribution ◽  
Platelet Volume ◽  
Platelet To Lymphocyte Ratio ◽  
Distribution Width ◽  
Lymphocyte Ratio ◽  
The Mean

AIM: The purpose of this study was to investigate the usefulness of the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) Mean Platelet Volume (MPV) and Red Cell Distribution Width (RDW) in the differential diagnosis and follow-up of patients with Bells Palsy.MATERIAL AND METHODS: Twenty-eight patients diagnosed with Bells Palsy and 28 control patients were included in the study. Serum samples were analysed retrospectively on the initial presentation and the seventh day of admission.RESULTS: On admission, the NLR was 1.7±1.2. The mean absolute neutrophil count was 6100 ± 900/mm^3 in Bells Palsy Group. NLR was 0.9 ± 0.2. The mean absolute neutrophil count was 4400 ± 1100/mm^3 in control group. Statistically, significant changes were not observed in NLR, PLR, MPV and RDW measurements in Bells Palsy group between House-Brackman Staging.CONCLUSION: Statistically significant changes in the neutrophil count and NLR were determined in the measurements between Bells Palsy and control group (p = 0.013, p = 0.016 respectively) on admission. A grade of the disease and NLR measurements had no statistically significant connection. RDW value was investigated for the first time in the literature for Bells Palsy patients.

scholarly journals Transcriptome-wide Association Study of Blood Cell Traits in African Ancestry and Hispanic/Latino Populations

2021 ◽  
Author(s):  
Jia Wen ◽  
Munan Xie ◽  
Bryce Rowland ◽  
Jonathan D. Rosen ◽  
Quan Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
African American ◽  
Blood Cell ◽  
Association Study ◽  
Target Genes ◽  
Prediction Models ◽  
African Ancestry ◽  
Reference Panel ◽  
European Ancestry ◽  
Hematological Trait

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Also, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including N=229 African American and N=381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, N = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (N = 27,955) and Hispanic/Latino (N = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p &lt; 1&times;10^(-4)) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (N=802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

Pharmacokinetic Interaction between 4′-Epidoxorubicin and the Multidrug Resistance Reverting Agent Quinine

1995 ◽  
Vol 50 (7-8) ◽  
pp. 565-570
Author(s):  
Martin Czejka ◽  
Suzan Bandak ◽  
Doris Simon ◽  
Johann Schiiller ◽  
Claudia Weiss ◽  
...  
Keyword(s):  
Blood Cell ◽  
Significant Influence ◽  
Red Blood Cell ◽  
Pharmacokinetic Interaction ◽  
Beta Phase ◽  
Initial Distribution ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Time Interval ◽  
The Mean

The serum and red blood cell (RBCs) disposition of epirubicin (EPR) after intravenous bolus injection without and with coadministered quinine (QUI) was investigated in patients undergoing a cyclic chemotherapy with EPR. QUI possesses a statistical significant influence on the EPR serum concentrations and, as a consequence, on the pharmacokinetic parameters for the initial distribution phase of EPR. Within the first 15 min after administration, EPR was distributed from the central compartiment distinctly faster in compare to the control, when QUI was preadministered (t1/2 = 6 min for the control group and t1/2 = 3 min with QUI; -46% , p < 0.05). Yet, in the beta-phase when drug-elimination predominates, no statistical significant influence of QUI in regard to EPR serum and RBC concentrations could be observed. Half-life of elimination was 9.5 h for the control group and 8.6 h for the QUI group (-10% ). The mean initial serum concentration (c0) was reduced significantly by QUI from 7359 ± 506 ng/ml to 4351 ± 1682 ng/ml (-42 % . p < 0.005). Furthermore. QUI caused a reduction of the serum bioavailability of EPR (expressed as AUC0-24-values) from 3404 ± 1008 ng/ml × h to 2359 ± 1073 ng/ml × h (-3 1 % , p < 0.05). Vd and Vdß were increased at about 90% and the mean total body clearance was accelerated from 45.3 to 148.7 ml/min, but due to the large standard deviations the calculated difference for these parameters was not statistically significant. In the observed time interval of 24 h, the red blood cell coefficient of distribution kRBC of EPR was lower if QUI was coadministered (kRBC = 1.25 ± 0.12 for the control group kRBC = 1.15 ± 0.13 under QUI; p < 0.04). The results point out that QUI induces an accelerated distribution of EPR from the blood into the tissue and that QUI additionally may have influence on the red-blood cell partitioning of EPR.

Toxicological evaluation and effects of oganophosphate compounds on hematological profile of juvenile common carps (Cyprinus carpio var. Communis)

2018 ◽  
Author(s):  
Imtiyaz Masood H. Balkhi, Feroz A. Shah Qayoom ◽  
Masood Feroz A. Shah and Bilal A. Bhat H Balkhi ◽  
Feroz A. Shah ◽  
Bilal A. Bhat
Keyword(s):  
Blood Cell ◽  
Cyprinus Carpio ◽  
Negative Impact ◽  
Haemoglobin Concentration ◽  
Toxicity Tests ◽  
Control Group ◽  
Toxicological Evaluation ◽  
Range Finding ◽  
Haematological Profile ◽  
The Mean

Present study was carried out to investigate the alterations in the haematological profile of juvenile common carp (Cyprinus carpio var. communis) against acute toxicity of organophosphorous compounds, dimethoate and chlorpyrifos. The fish were divided into 5 different experimental groups for range finding tests on the basis of which the doses for definitive tests were selected. The acute bioassay toxicity tests were carried out in triplicates for 96 hours with a control group run parallel to the experiment. Data obtained was analyzed as per Finney’s probit to determine LC50 values. The mean lethal concentration was found 1.1ppm and 3.8ppb respectively for dimethoate and chlorpyrifos. The samples investigated for various haematological parameters such as haemoglobin concentration (Hb), Red blood cell (TEC) and White blood cell (TLC and DLC) counts the heamatocrit (Ht) level, the mean corpuscular volume (MCV) and the mean corpuscular haemoglobin (MCH). Packed cell volume (PCV) and Erythrocyte sedimentation rate (ESR) showed a negative impact of pesticide treated fishes when compared with control. Hb, TEC and Ht were found lower while as ESR and TLC were recorded higher than the control specimens. MCV and MCH showed statistically insignificant differences when compared with control. In DLC, monocyte lymphocyte, neutrophil and basophils were found increased while as eosinophil count was found unaffected than the normal. Studies suggested that the pesticides are potential toxicants for common carps among which chlorpyrifos was found to elicit profound changes intense than dimethoate.

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