White blood cells and subtypes in HFE p.C282Y and wild-type homozygotes in the Hemochromatosis and Iron Overload Screening Study

2017 ◽  
Vol 63 ◽  
pp. 9-14
Author(s):  
James C. Barton ◽  
J. Clayborn Barton ◽  
Ronald T. Acton
Keyword(s):  
Iron Overload ◽  
Blood Cells ◽  
White Blood Cells ◽  
Wild Type ◽  
Screening Study

scholarly journals Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2148-2159 ◽  
Author(s):  
Harshal H. Nandurkar ◽  
Lorraine Robb ◽  
David Tarlinton ◽  
Louise Barnett ◽  
Frank Köntgen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
White Blood Cells ◽  
Null Mutation ◽  
Wild Type ◽  
Normal Numbers ◽  
Interleukin 11 ◽  
Marrow Cells

Abstract Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11Rα, we have generated mice with a null mutation of IL11Ra (IL11Ra−/−) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra−/− bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra−/− mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra−/− mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra−/− and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra−/− and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.

Hedgehog Signaling Regulates HSC Proliferation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1390-1390
Author(s):  
Akil Merchant ◽  
Giselle Joseph ◽  
William Matsui
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Blood Cells ◽  
White Blood Cells ◽  
Wild Type ◽  
Serial Blood ◽  
Myeloid Progenitor ◽  
Hh Signaling ◽  
Progenitor Compartment

Abstract Hedgehog (Hh) signaling is essential for normal development and is dysregulated in many cancers. Hh signaling is active in normal bone marrow and the majority of acute myeloid leukemias, however, the precise role of Hh signaling and its positive effector Gli1 in normal or malignant hematopoiesis is not known. We have analyzed the bone marrow of Gli1 null mice to understand the role of this transcription factor in normal hematopoiesis in order to gain insight into its potential role in leukemia. Gli1 null mice develop normally and have normal peripheral blood counts but the bone marrow shows skewing of the c-Kit+Sca1+Lin-neg (KSL) progenitor compartment with increased CD34negKSL long-term HSC (LT-HSC) and decreased 34+KSL short-term HSC (ST-HSC). An analogous difference was observed in the c-Kit+Sca1negLinneg (KL) myeloid progenitor compartment with an increase in FcRγlowCD34+KL common myeloid progenitors (CMP) and decrease in the FcRγhighCD34+KL granulocyte monocyte progenitors (GMP). We speculated that these differences could be due to impaired cell cycle since both the ST-HSC and GMP are more proliferative than LT-HSC and CMP, respectively. Cell cycle analysis by DNA content and BrdU pulse labeling (100mg/kg IP 14 hours prior to analysis) revealed a marked decrease of proliferation in the LT-HSC, ST-HSC, CMP, and GMP compartments of Gli1 null mice. We supported this conclusion by demonstrating that the bone marrow of Gli1 null mice are relatively radio-resistant. Mice exposed to 400 cGy of total body irradiation followed with serial blood counts revealed less severe nadir, but delayed rebound of white blood cells in Gli1 null mice. We further hypothesized that although Gli1 appears to be dispensable for steady-state peripheral hematopoiesis, it might be necessary for rapid proliferation of progenitors needed during stressed hematopoiesis. In brain development, where Hh signaling is much better understood, active Hh signaling is critical for regulating proliferation of neural stem cells and Gli1 activity significantly increases after depletion of neural progenitors with chemotherapy (Bai et al., Development, 2002). To extend this observation to hematopoiesis, we treated Gli1 null mice and wild-type litter-mates with 5-fluorouracil (5-FU) at 100mg/kg and measured serial blood counts. Gli1 null mice had a delayed recovery of total white blood cells and neutrophil counts at 6 days after 5-FU, but this difference normalized by 20 days after treatment. To confirm that this difference was due to impaired proliferation and not increased sensitivity to 5-FU, we treated Gli1 null and wild-type mice with G-CSF (10mcg/kg/day) for three days to stimulate neutrophil proliferation. Confirming our hypothesis, we observed an attenuated neutrophil response in G-CSF stimulated Gli1 null mice. In summary, we have demonstrated that Gli1 loss leads to decreased HSC and myeloid progenitor proliferation, which has important functional consequences for stress hematopoiesis. These data suggest that abnormal Hh activity in leukemia may be important for driving the uncontrolled proliferation of cancer cells. Gli1 null mice were a kind gift from Alexandra Joyner, Memorial Sloan-Kettering Cancer Center

scholarly journals Selectins and neutrophil traffic: margination and Streptococcus pneumoniae-induced emigration in murine lungs.

1996 ◽  
Vol 184 (2) ◽  
pp. 639-645 ◽  
Author(s):  
J P Mizgerd ◽  
B B Meek ◽  
G J Kutkoski ◽  
D C Bullard ◽  
A L Beaudet ◽  
...  
Keyword(s):  
Body Weight ◽  
Streptococcus Pneumoniae ◽  
Blood Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
Intratracheal Instillation ◽  
Wild Type ◽  
Intravenous Injections ◽  
Pulmonary Capillaries ◽  
Pulmonary Microvessels

The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both E- and P-selectins (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both L- and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/- 0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increased margination of neutrophils within pulmonary capillaries (39.7 +/- 9.4 vs. 4.6 +/- 1.1 neutrophil profiles per 100 red blood cell profiles) but no change in margination within noncapillary pulmonary microvessels. After intratracheal instillation of Streptococcus pneumoniae, lungs of E/P mutants displayed increased neutrophil emigration (564 +/- 92 vs. 116 +/- 19 neutrophils per 100 alveolar profiles), edema (5.3 +/- 1.5 vs. 1.5 +/- 0.4 microliter/g body weight), and histologic evidence of lung injury compared with those in wild-type (WT). Fucoidin treatment did not affect neutrophil emigration during streptococcal pneumonia in WT or E/P mice. During pneumonia, the number of white blood cells (WBC) tethered to or spread upon the noncapillary vessel endothelium increased in both WT and E/P lungs. These are the first data demonstrating that neutrophil margination in uninfected pulmonary capillaries does not require E- and P-selectins; that streptococcal pneumonia induces an E- and P-selectin-independent increase in WBC interactions with noncapillary endothelium; and that migration of neutrophils to alveoli can occur despite deficiency or inhibition of all of the known selectins.

scholarly journals 5 NEUTRAL SEGREGATION OF DONOR CELL MITOCHONDRIA IN FETAL AND ADULT TISSUES OF SOMATIC CELL CLONES IN CATTLE

2005 ◽  
Vol 17 (2) ◽  
pp. 153
Author(s):  
F. Viramontes ◽  
F. Filion ◽  
L.C. Smith
Keyword(s):  
Blood Cells ◽  
Bos Taurus ◽  
White Blood Cells ◽  
Bos Indicus ◽  
Pcr Amplification ◽  
Donor Cell ◽  
Wild Type ◽  
Mtdna Mutation ◽  
D Loop ◽  
The Mean

Until now, animal cloning has been extremely inefficient: only 1–2% of nuclear transfer (NT) clones survive to birth. Some of these anomalies may be related to an incompatibility between nuclear and mitochondrial genes (Cummins JM 2001 Hum. Reprod. Update 7, 217–228). Controversy exists as to the levels of donor cell mitochondrial DNA (mtDNA) inheritance in somatic clones (heteroplasmy). Whereas some researchers found very low quantities (0.1–4%) (Steinborn R et al. 2000 Nat. Genet. 25, 255–257), others found levels of heteroplasmy ranging from 6 to 40% (Takeda et al. Mol. Reprod. Dev. 64, 429–437). Since it remains unclear whether mtDNA segregation is neutral or selective, the purpose of this study was to analyze the transmission of the mtDNA from donor somatic cells in fetal and adult clones using a particular mtDNA marker (mtDNA Bos taurus with one mutation in the D-loop of 40 base pairs plus than the wild type). Fibroblasts from a fetus of 60 days were used as donor cells. The fetus was produced by artificial insemination of a Holstein (Bos taurus) heifer carrying an mtDNA mutation with semen from a Zebu (Bos indicus) bull. Oocytes derived from slaughterhouse ovaries of Holstein cows carrying wild-type mtDNA were used as recipient cells. The presence of the mutated mtDNA from the donor cell (heteroplasmy) was analyzed in a male cloned fetus of 60 days and in three adult male clones at 18 months of age. Heteroplasmy was detected in 7 tissues in the foetus: muscle, skin, stomach, testicle, thymus, tongue, and umbilical cord. Three tissues were analyzed from the adult clones: semen, skin, and white blood cells. Heteroplasmy was detected in all the tissues by nested PCR amplification of the D-loop and analyzed by ANOVA and Tukey-Kramer multiple comparison test. The mean (%) of the mutated mtDNA of the donor cell in the seven tissues of the60-day-old fetus was 1.14 ± 0.34 (SEM). There was no differences in the means of heteroplasmy (%) between the tissues of the fetus (P > 0.05). The mean level of heteroplasmy in the three adult clones analyzed (clones A, B, and C) was 1.41 ± 0.18 (SEM). Analysis of heteroplasmy between the tissues of each clone showed no differences (P > 0.05) with the exception of clone B, where semen was different (P < 0.05) from white blood cells. There were significant differences (P < 0.05) between some clones (taking together all the results of all tissues of each clone). The heteroplasmy in clone B (%) (2.59 ± 0.18 SEM) was different (P < 0.05) from that of both clone A (1.04 ± 0.18) and clone C (1.46 ± 0.18). There was no difference between the heteroplasmy (%) of clone A and that of clone C (P > 0.05). These results show that the tissues of the fetus and the adult clones were heteroplasmic at similar levels, suggesting neutral segregation of the donor cell mtDNA during development and tissue differentiation.

Impaired neutrophil maturation in truncated murine G-CSF receptor–transgenic mice

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 2990-2995 ◽  
Author(s):  
Tetsuo Mitsui ◽  
Sumiko Watanabe ◽  
Yoshihiro Taniguchi ◽  
Sachiyo Hanada ◽  
Yasuhiro Ebihara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
White Blood Cells ◽  
Acute Myelocytic Leukemia ◽  
Wild Type ◽  
Maturation Arrest ◽  
Mutant Receptor ◽  
Cell Counts ◽  
Marrow Cells

Abstract Severe congenital neutropenia (SCN) is a hematopoietic disorder characterized by neutropenia in peripheral blood and maturation arrest of neutrophil precursors in bone marrow. Patients with SCN may evolve to have myelodysplastic syndrome or acute myelocytic leukemia. In approximately 20% of SCN cases, a truncation mutation is found in the cytoplasmic region of the granulocyte colony-stimulating factor receptor (G-CSFR). We then generated mice carrying murine wild-type G-CSFR and its mutants equivalent to truncations at amino acids 718 and 731 in human G-CSFR, those were reported to be related to leukemic transformation of SCN. Although numbers of peripheral white blood cells, red blood cells, and platelets did not differ among mutant and wild-type G-CSFR transgenic (Tg) mice, both of the mutant receptor Tg mice had one third of peripheral neutrophil cell counts compared with wild-type receptor Tg mice. The mutant receptor Tg mice also showed impaired resistance to the infection with Staphylococcus aureus. Moreover, bone marrow of these Tg mice had an increased percentage of immature myeloid cells, a feature of SCN. This maturation arrest was also observed in in vitro cultures of bone marrow cells of truncated G-CSFR Tg mice under G-CSF stimulation. In addition, clonal culture of bone marrow cells of the truncated G-CSFR Tg mice showed the hypersensitivity to G-CSF in myeloid progenitors. Our Tg mice may be useful in the analysis of the role of truncated G-CSFR in SCN pathobiology.

scholarly journals Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2148-2159 ◽  
Author(s):  
Harshal H. Nandurkar ◽  
Lorraine Robb ◽  
David Tarlinton ◽  
Louise Barnett ◽  
Frank Köntgen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
White Blood Cells ◽  
Null Mutation ◽  
Wild Type ◽  
Normal Numbers ◽  
Interleukin 11 ◽  
Marrow Cells

Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11Rα, we have generated mice with a null mutation of IL11Ra (IL11Ra−/−) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra−/− bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra−/− mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra−/− mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra−/− and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra−/− and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.

Abstract 15892: mRNA Stability Hu Proteins Regulate Human Cardiac Sodium Channel Expression

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Anyu Zhou ◽  
Ian Greener ◽  
An Xie ◽  
Guangbin Shi ◽  
Kai-Chien Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sodium Channel ◽  
Mrna Stability ◽  
Blood Cells ◽  
White Blood Cells ◽  
Mrna Abundance ◽  
Wild Type ◽  
Hu Protein ◽  
Hu Proteins ◽  
Cardiac Sodium Channel

Human heart failure has been associated with reduced cardiac Nav1.5 Na+ channel current and SCN5A mRNA abundance. We hypothesized that reduced mRNA stability would contribute to the reduction of SCN5A mRNA. Hu proteins are known to contribute to mRNA stability The SCN5A mRNA 3’-untranslated region (UTR) contains two sets of putative Hu protein binding site. Over-expression of HuR and HuB in cardiomyocytes derived from primary human fetal ventricle increased wild-type SCN5A mRNA 46.3% (P=0.004) and 60.7% (P=0.008), respectively. Knocking down of HuR or HuB by siRNA decreased SCN5A mRNA by 27.5% (P=0.000) and 20.4% (P=0.02). RNA immunoprecipitation showed HuR associated with SCN5A mRNA. This suggested Hu family proteins might play an important role in upregulation of SCN5A expression by stabilizing SCN5A mRNA. In addition, we found HuR mRNA decreased 38.9% (P=0.034) in peripheral white blood cells of heart failure patients with implanted cardioverter-defibrillator (ICD) and evidence of appropriate event-driven therapy compared to control subjects. The decrease of HuR mRNA correlated with a reduction of wild-type SCN5A mRNA abundance in white blood cells from these patients. Our results demonstrate an additional layer of SCN5A posttranscriptional regulation in addition to alternative splicing that can contribute to sodium channel down-regulation in heart failure. Our results also suggest that circulating HU protein assessment may be useful in arrhythmic risk stratification and that exogenous HU protein overexpression may help reduce arrhythmic risk in heart failure.

Ultrastructural changes in murine lymphoma cells exposed to ultraviolet-A radiation

1991 ◽  
Vol 49 ◽  
pp. 104-105
Author(s):  
Delma P. Thomas ◽  
Dianne E. Godar
Keyword(s):  
Medical Devices ◽  
Blood Cells ◽  
White Blood Cells ◽  
Consumer Products ◽  
Ultrastructural Changes ◽  
Ultraviolet A ◽  
Uv Spectrum ◽  
Lymphoma Cells ◽  
Murine Lymphoma ◽  
Transmission Electron

Ultraviolet radiation (UVR) from all three waveband regions of the UV spectrum, UVA (320-400 nm), UVB (290-320 nm), and UVC (200-290 nm), can be emitted by some medical devices and consumer products. Sunlamps can expose the blood to a considerable amount of UVR, particularly UVA and/or UVB. The percent transmission of each waveband through the epidermis to the dermis, which contains blood, increases in the order of increasing wavelength: UVC (10%) < UVB (20%) < UVA (30%). To investigate the effects of UVR on white blood cells, we chose transmission electron microscopy to examine the ultrastructure changes in L5178Y-R murine lymphoma cells.

The Effect of Red Blood Cells on the ADP-induced Aggregation of Human Platelets in Flow Through Tubes

1990 ◽  
Vol 63 (01) ◽  
pp. 112-121 ◽  
Author(s):  
David N Bell ◽  
Samira Spain ◽  
Harry L Goldsmith
Keyword(s):  
Platelet Aggregation ◽  
Shear Rate ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Platelet Rich Plasma ◽  
Mean Transit Time ◽  
White Blood Cells ◽  
Aggregate Size ◽  
Human Platelets ◽  
Induced Aggregation

SummaryThe effect of red blood cells, rbc, and shear rate on the ADPinduced aggregation of platelets in whole blood, WB, flowing through polyethylene tubing was studied using a previously described technique (1). Effluent WB was collected into 0.5% glutaraldehyde and the red blood cells removed by centrifugation through Percoll. At 23°C the rate of single platelet aggregtion was upt to 9× greater in WB than previously found in platelet-rich plasma (2) at mean tube shear rates Ḡ = 41.9,335, and 1,920 s−1, and at both 0.2 and 1.0 µM ADP. At 0.2 pM ADP, the rate of aggregation was greatest at Ḡ = 41.9 s−1 over the first 1.7 s mean transit time through the flow tube, t, but decreased steadily with time. At Ḡ ≥335 s−1 the rate of aggregation increased between t = 1.7 and 8.6 s; however, aggregate size decreased with increasing shear rate. At 1.0 µM ADP, the initial rate of single platelet aggregation was still highest at Ḡ = 41.9 s1 where large aggregates up to several millimeters in diameter containing rbc formed by t = 43 s. At this ADP concentration, aggregate size was still limited at Ḡ ≥335 s−1 but the rate of single platelet aggregation was markedly greater than at 0.2 pM ADP. By t = 43 s, no single platelets remained and rbc were not incorporated into aggregates. Although aggregate size increased slowly, large aggregates eventually formed. White blood cells were not significantly incorporated into aggregates at any shear rate or ADP concentration. Since the present technique did not induce platelet thromboxane A2 formation or cause cell lysis, these experiments provide evidence for a purely mechanical effect of rbc in augmenting platelet aggregation in WB.

White blood cells levels and PCOS: direct and indirect relationship with insulin resistance, but not with hyperandogenemia

2013 ◽  
Author(s):  
Olga Papalou ◽  
Sarantis Livadas ◽  
Athanasios Karachalios ◽  
Nektarios Benetatos ◽  
George Boutzios ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Cells ◽  
White Blood Cells ◽  
Indirect Relationship
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