WorldWideScience

Sample records for deficient red cells

  1. Red cell pyruvate kinase deficiency in Southern Sardinia.

    Science.gov (United States)

    Perseu, L; Giagu, N; Satta, S; Sollaino, M C; Congiu, R; Galanello, R

    2010-12-15

    Pyruvate kinase (PK) deficiency is the most frequent red cell enzymatic defect responsible for hereditary non-spherocytic hemolytic anemia. The clinical picture is quite variable and the reasons of this variability have been only partially clarified. We report the clinical description and the extended molecular analysis in 3 PK deficient patients with clinical phenotype of variable severity. We studied the clinical and hematological aspects of 3 patients and analyzed the following genes: pyruvate kinase-R, glucose-6-phosphate-dehydrogenase, α-globin, uridindiphosphoglucuronil transferase and HFE. One patient (A) with a severe clinical picture resulted homozygote for exon 8 nt994A substitution, the other 2 (brothers) were compound heterozygotes for exon 8 nt994A and exon 11 nt1456T mutation. One of the two brothers with a more severe phenotype coinherited also had G6PD deficiency, while both had microcytosis due to the homozygosity for the non-deletional form of α-thalassemia ATG→ACG substitution at the initiation codon of the alpha2 globin gene. Our results suggest that extended molecular analysis is useful for studying how several interacting gene mutations contribute to the clinical variability of pyruvate kinase deficiency.

  2. Estimated red blood cell thickness in microcytic anemia due to iron deficiency anemia and thalassemia

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2009-05-01

    Full Text Available "nAnemia is one of the most common hematological disorders that are still the present in all countries around the world. Microcytic anemia is a specific kind of anemia presenting with small red blood cell. In this paper, the author discusses on the estimated red blood cell thickness, a new proposed parameter, comparing between that of iron deficiency anemia and thalassemia and further extrapolate on the clinical implication.

  3. Red cell pyruvate kinase deficiency: from genetics to clinical manifestations.

    Science.gov (United States)

    Zanella, A; Bianchi, P

    2000-03-01

    Pyruvate kinase deficiency is the most frequent enzyme abnormality of the Embden-Meyerhof pathway causing hereditary non-spherocytic haemolytic anaemia. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life-threatening neonatal anaemia and jaundice necessitating exchange transfusions. Splenectomy should be reserved for young patients who require regular blood transfusions. The gene encoding for pyruvate kinase (PK-LR) has been localized to the long arm of chromosome I; the cDNA of R-type is 2060 bp long and codes for 574 amino acids. More than 130 different mutations, mostly missense, have so far been described in association with PK deficiency, 1529A and 1456T being considered to be the most common mutations in Caucasians. Analysis of the three-dimensional structure of the enzyme may help in predicting the severity of the molecular defect. Further data on clinical features of homozygous patients are needed, at least for some mutations, to allow a more precise genotype/phenotype correlation.

  4. Heme oxygenase-1 deficiency alters erythroblastic island formation, steady-state erythropoiesis and red blood cell lifespan in mice.

    Science.gov (United States)

    Fraser, Stuart T; Midwinter, Robyn G; Coupland, Lucy A; Kong, Stephanie; Berger, Birgit S; Yeo, Jia Hao; Andrade, Osvaldo Cooley; Cromer, Deborah; Suarna, Cacang; Lam, Magda; Maghzal, Ghassan J; Chong, Beng H; Parish, Christopher R; Stocker, Roland

    2015-05-01

    Heme oxygenase-1 is critical for iron recycling during red blood cell turnover, whereas its impact on steady-state erythropoiesis and red blood cell lifespan is not known. We show here that in 8- to 14-week old mice, heme oxygenase-1 deficiency adversely affects steady-state erythropoiesis in the bone marrow. This is manifested by a decrease in Ter-119(+)-erythroid cells, abnormal adhesion molecule expression on macrophages and erythroid cells, and a greatly diminished ability to form erythroblastic islands. Compared with wild-type animals, red blood cell size and hemoglobin content are decreased, while the number of circulating red blood cells is increased in heme oxygenase-1 deficient mice, overall leading to microcytic anemia. Heme oxygenase-1 deficiency increases oxidative stress in circulating red blood cells and greatly decreases the frequency of macrophages expressing the phosphatidylserine receptor Tim4 in bone marrow, spleen and liver. Heme oxygenase-1 deficiency increases spleen weight and Ter119(+)-erythroid cells in the spleen, although α4β1-integrin expression by these cells and splenic macrophages positive for vascular cell adhesion molecule 1 are both decreased. Red blood cell lifespan is prolonged in heme oxygenase-1 deficient mice compared with wild-type mice. Our findings suggest that while macrophages and relevant receptors required for red blood cell formation and removal are substantially depleted in heme oxygenase-1 deficient mice, the extent of anemia in these mice may be ameliorated by the prolonged lifespan of their oxidatively stressed erythrocytes.

  5. Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.

    Science.gov (United States)

    Sayour, Elias J; Mousallem, Talal; Van Mater, David; Wang, Endi; Martin, Paul; Buckley, Rebecca H; Barfield, Raymond C

    2016-10-01

    Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids. © 2016 Wiley Periodicals, Inc.

  6. Red blood cell PK deficiency: An update of PK-LR gene mutation database.

    Science.gov (United States)

    Canu, Giulia; De Bonis, Maria; Minucci, Angelo; Capoluongo, Ettore

    2016-03-01

    Pyruvate kinase (PK) deficiency is known as being the most common cause of chronic nonspherocytic hemolytic anemia (CNSHA). Clinical PK deficiency is transmitted as an autosomal recessive trait, that can segregate neither in homozygous or in a compound heterozygous modality, respectively. Two PK genes are present in mammals: the pyruvate kinase liver and red blood cells (PK-LR) and the pyruvate kinase muscle (PK-M), of which only the first encodes for the isoenzymes normally expressed in the red blood cells (R-type) and in the liver (L-type). Several reports have been published describing a large variety of genetic defects in PK-LR gene associated to CNSHA. Herein, we present a review of about 250 published mutations and six polymorphisms in PK-LR gene with the corresponding clinical and molecular data. We consulted the PubMed website for searching mutations and papers, along with two main databases: the Leiden Open Variation Database (LOVD, https://grenada.lumc.nl/LOVD2/mendelian_genes/home.php?select_db=PKLR) and Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PKLR) for selecting, reviewing and listing the annotated PK-LR gene mutations present in literature. This paper is aimed to provide useful information to clinicians and laboratory professionals regarding overall reported PK-LR gene mutations, also giving the opportunity to harmonize data regarding PK-deficient individuals.

  7. Red blood cell distribution width and iron deficiency anemia among pregnant Sudanese women

    Directory of Open Access Journals (Sweden)

    Abdelrahman Esam G

    2012-12-01

    Full Text Available Abstract Background Iron deficiency anemia (IDA is a major health problem during pregnancy and it has adverse effects on the mother and the newborn. Red cell distribution width (RDW, which is a quantitative measure for red cell size variation (anisocytosis, is a predictor of IDA. Little is known regarding RDW and IDA during pregnancy. Methods A cross sectional study was conducted at the antenatal clinic of Khartoum Hospital, Sudan, to determine the performance of RDW in the diagnosis of IDA using serum ferritin as a gold standard. Results Among 194 pregnant women with a gestational period of 21.4 ± 6.5 weeks, 57 (29.4% had IDA according to serum ferritin levels (14.5. The sensitivity, specificity, positive predictive value, and negative predictive value of RDW where serum ferritin was the gold standard were 43.8% (95% CI: 31.4–57.0%, 73.7% (95% CI: 65.8–80.5%, 41.0% (95% CI: 29.2–53.6%, and 76.0% (95% CI: 68.1–82.6%, respectively. Conclusions In this study, we found that RDW has a poor performance in diagnosing IDA among pregnant women compared with serum ferritin as the gold standard. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1721072967826303

  8. Apoptosis and morphological alterations after UVA irradiation in red blood cells of p53 deficient Japanese medaka (Oryzias latipes).

    Science.gov (United States)

    Sayed, Alla El-Din Hamid; Watanabe-Asaka, Tomomi; Oda, Shoji; Mitani, Hiroshi

    2016-08-01

    Morphological alterations in red blood cells were described as hematological bioindicators of UVA exposure to investigate the sensitivity to UVA in wild type Japanese medaka (Oryzias latipes) and a p53 deficient mutant. The fewer abnormal red blood cells were observed in the p53 mutant fish under the control conditions. After exposure to different doses of UVA radiation (15min, 30min and 60min/day for 3days), cellular and nuclear alterations in red blood cells were analyzed in the UVA exposed fish compared with non-exposed controls and those alterations included acanthocytes, cell membrane lysis, swollen cells, teardrop-like cell, hemolyzed cells and sickle cells. Those alterations were increased after the UVA exposure both in wild type and the p53 deficient fish. Moreover, apoptosis analyzed by acridine orange assay showed increased number of apoptosis in red blood cells at the higher UVA exposure dose. No micronuclei but nuclear abnormalities as eccentric nucleus, nuclear budding, deformed nucleus, and bilobed nucleus were observed in each group. These results suggested that UVA exposure induced both p53 dependent and independent apoptosis and morphological alterations in red blood cells but less sensitive to UVA than Wild type in medaka fish.

  9. Red Cell Indices and Formulas Used in Differentiation of β-Thalassemia Trait from Iron Deficiency in Thai Adults.

    Science.gov (United States)

    Plengsuree, Soontharee; Punyamung, Manoo; Yanola, Jintana; Nanta, Siriporn; Jaiping, Kanokwan; Maneewong, Kritsanee; Wongwiwatthananukit, Sanchai; Pornprasert, Sakorn

    2015-01-01

    β-Thalassemia (β-thal) and iron deficiency cause most microcytic anemias. Red cell indices and formulas have been established as simple, fast, and inexpensive in discrimination between these two hematological disorders in school children. However, whether these formulas could be applied to diagnose β-thal trait and iron deficiency in adult Thai subjects is unclear. The aim of this study was to examine the diagnostic accuracy of five red cell indices [red blood cell (RBC) counts, mean corpuscular volume (MCV), mean corpuscular hemoglobin (Hb) (MCH), mean corpuscular Hb concentration (MCHC), and red cell distribution width (RDW)] and nine formulas (RDW/RBC, RDW Index, Sirdah, Green and King, Mentzer, England and Fraser, Ehsani, Srivastava and Shine and Lal). Their sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), efficiency, and Youden's Index were analyzed in 102 β-thal trait and 64 iron deficiency adult Thai subjects. The RDW/RBC formula proved to be the most reliable index as they had 100.0% specificity and PPV and the highest efficiency (94.58%) and Youden's Index (91.18%), as well as high sensitivity (91.18%) and NPV (87.67%). Therefore, this formula could be used in initial discrimination of β-thal trait from iron deficiency in adult Thai subjects.

  10. The Effect of Iron Deficiency on Osmotic Sensitivity of Red Blood Cells from Neonatal Rats and Their Mothers.

    Science.gov (United States)

    Al-Hashimi, L Mossa; Gambling, Lorraine; McArdle, H J

    2015-12-01

    Iron deficiency during pregnancy has many effects on both the mother and her developing foetus. These can be both short and long term. One effect is an alteration in fatty acid metabolism and we hypothesised that these changes may result in alterations in membrane function and structure. In order to test this hypothesis, we measured osmotic sensitivity in red blood cells isolated from neonates and their mothers at different times following birth. We fed female rats control or iron-deficient diets for 4 weeks prior to mating and kept them on the same diet until term. At that time, we returned one group of deficient dams to the control diet. The others were kept on the same diet. We showed that iron deficiency results in a decrease in osmotic sensitivity in the mothers but not in their neonates. Returning the dams to the control diet resulted in a return of their red cell osmotic sensitivity to control levels. In the neonates, there was no recovery in haematocrit or in any other parameter, though they did not get any worse, in contrast to the pups being suckled by deficient mothers. The data show two things. The first is that following birth, the mother restores her own iron stores at the expense of the pups, and secondly, there are differences in properties and sensitivities between red cells from mothers and their neonates. This latter observation cannot be explained by differences in the membrane fatty acid profiles, which were not significantly different.

  11. Peroxiredoxin I deficiency attenuates phagocytic capacity of macrophage in clearance of the red blood cells damaged by oxidative stress.

    Science.gov (United States)

    Han, Ying-Hao; Kwon, Taeho; Kim, Sun-Uk; Ha, Hye-Lin; Lee, Tae-Hoon; Kim, Jin-Man; Jo, Eun-Kyeong; Kim, Bo Yeon; Yoon, Do Young; Yu, Dae-Yeul

    2012-10-01

    The role of peroxiredoxin (Prx) I as an erythrocyte antioxidant defense in red blood cells (RBCs) is controversial. Here we investigated the function of Prx I by using Prx I(-/-) and Prx I/II(-/-) mice. Prx I(-/-) mice exhibited a normal blood profile. However, Prx I/II(-/-) mice showed more significantly increased Heinz body formation as compared with Prx II(-/-) mice. The clearance rate of Heinz body-containing RBCs in Prx I(-/-) mice decreased significantly through the treatment of aniline hydrochloride (AH) compared with wild-type mice. Prx I deficiency decreased the phagocytic capacity of macrophage in clearing Heinz body-containing RBCs. Our data demonstrate that Prx I deficiency did not cause hemolytic anemia, but showed that further increased hemolytic anemia symptoms in Prx II(-/-) mice by attenuating phagocytic capacity of macrophage in oxidative stress damaged RBCs, suggesting a novel role of Prx I in phagocytosis of macrophage.

  12. Red Blood Cell Distribution Width and the Platelet Count in Iron-deficient Children Aged 0.5-3 Years.

    Science.gov (United States)

    Akkermans, M D; Uijterschout, L; Vloemans, J; Teunisse, P P; Hudig, F; Bubbers, S; Verbruggen, S; Veldhorst, M; de Leeuw, T G; van Goudoever, J B; Brus, F

    2015-01-01

    Early detection of iron deficiency (ID) and iron deficiency anemia (IDA) in young children is important to prevent impaired neurodevelopment. Unfortunately, many biomarkers of ID are influenced by infection, thus limiting their usefulness. The aim of this study was to investigate the value of red blood cell distribution width (RDW) and the platelet count for detecting ID(A) among otherwise healthy children. A multicenter prospective observational study was conducted in the Netherlands to investigate the prevalence of ID(A) in 400 healthy children aged 0.5-3 years. ID was defined as serum ferritin (SF) count were determined in the complete blood cell count. RDW was inversely correlated with SF and not associated with CRP. Calculated cutoff values for RDW to detect ID and IDA gave a relatively low sensitivity (53.1% and 57.1%, respectively) and specificity (64.7% and 69.9%, respectively). Anemic children with a RDW >14.3% had a 2.7 higher odds (95% confidence interval [CI]: 1.2-6.3) to be iron deficient, compared with anemic children with a RDW count showed a large range in both ID and non-ID children. In conclusion, RDW can be helpful for identifying ID as the cause of anemia in 0.5- to 3-year-old children, but not as primary biomarker of ID(A). RDW values are not influenced by the presence of infection. There appears to be no role for the platelet count in diagnosing ID(A) in this group of children.

  13. Peroxiredoxin I deficiency attenuates phagocytic capacity of macrophage in clearance of the red blood cells damaged by oxidative stress

    Directory of Open Access Journals (Sweden)

    Ying-Hao Han1,8,#, Taeho Kwon1,7,#, Sun-Uk Kim1,2,#, Hye-Lin Ha1, Tae-Hoon Lee1,3, Jin-Man Kim4, Eun-Kyeong Jo5, Bo Yeon Kim6, Do Young Yoon7 & Dae-Yeul Yu1,*

    2012-10-01

    Full Text Available The role of peroxiredoxin (Prx I as an erythrocyte antioxidantdefense in red blood cells (RBCs is controversial. Here weinvestigated the function of Prx I by using Prx I–⁄– and Prx I/II–⁄–mice. Prx I–⁄– mice exhibited a normal blood profile. However,Prx I/II–⁄– mice showed more significantly increased Heinz bodyformation as compared with Prx II–⁄– mice. The clearance rate ofHeinz body-containing RBCs in Prx I–⁄– mice decreasedsignificantly through the treatment of aniline hydrochloride (AHcompared with wild-type mice. Prx I deficiency decreased thephagocytic capacity of macrophage in clearing Heinz bodycontainingRBCs. Our data demonstrate that Prx I deficiency didnot cause hemolytic anemia, but showed that further increasedhemolytic anemia symptoms in Prx II–⁄– mice by attenuatingphagocytic capacity of macrophage in oxidative stress damagedRBCs, suggesting a novel role of Prx I in phagocytosis ofmacrophage.

  14. The use of primaquine in malaria infected patients with red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency in Myanmar.

    Science.gov (United States)

    Myat-Phone-Kyaw; Myint-Oo; Aung-Naing; Aye-Lwin-Htwe

    1994-12-01

    32 subjects with Plasmodium falciparum gametocytes, and 31 cases with Plasmodium vivax infection from two military hospitals (Lashio, Mandalay) were treated with quinine 600 mg three times a day for 7 days followed by primaquine 45 mg single dose for gametocytes and 45 mg weekly x 8 weeks for vivax malaria. Although screening of red cell glucose-6-phosphate dehydrogenase (G6PD) was done prior to primaquine treatment, G6PD deficient subjects were not excluded from the trial. 20 patients hemizygous for mild G6PD deficiency (GdB- variant), 2 patients hemizygous for severe deficiency (Gd-Myanmar variant) completed the trial. No case of acute hemolysis was observed in all 22 patients with two genotypes of red cell G6PD deficiency status. Therefore, a single dose of primaquine 45 mg and/or weekly for 8 weeks is adequate for the treatment of patients with P. falciparum gametocytes and/or P. vivax malaria ignoring these red cell G6PD enzyme deficient variants in Myanmar.

  15. Red blood cell production

    Science.gov (United States)

    ... to one part of the body or another. Red blood cells are an important element of blood. Their job ... is carried to and eliminated by the lungs. Red blood cells are formed in the red bone marrow of ...

  16. Red cell indices and discriminant functions in the detection of beta-thalassaemia trait in a population with high prevalence of iron deficiency anaemia.

    Science.gov (United States)

    Madan, N; Sikka, M; Sharma, S; Rusia, U; Kela, K

    1999-01-01

    Red cell indices and discriminant functions were studied in 463 heterozygous beta-thalassaemics (337 without iron deficiency, 126 with iron deficiency) and 195 patients of iron deficiency anaemia (IDA) to ascertain their utility in the detection of betathalassaemia trait (BTT). Majority of traits in both groups had an elevated RBC count (> or = 5.0 x 10(12)/L). The counts were significantly higher than of patients with IDA, only 4.6% of whom had this degree of erythrocytosis. Mean Hb concentration was significantly higher in traits as compared to iron deficient subjects (p < 0.0001). Mean MCV and MCH were significantly (p < 0.0001) lower in traits more so in those with ID as compared to patients of IDA. MCV < 80 fl and MCH < 27 pg were found to be sensitive markers in the detection of traits even in the presence of ID. Of the four discriminant functions studied MCSQ was found to be most sensitive in detection of BTT and it identified 97.9% traits. DF of England and Fraser was most specific for BTT being < 8.4 in only 6.2% patients with IDA. Detection of erythrocytosis especially in the presence of mild anaemia and calculation of discriminant functions derived from red cell indices were found to play an important role in screening for BTT even in the presence of ID and helped identify those patients who required further laboratory evaluation.

  17. A new red cell index and portable RBC analyzer for screening of iron deficiency and Thalassemia minor in a Chinese population.

    Science.gov (United States)

    Tong, Lieshu; Kauer, Josef; Wachsmann-Hogiu, Sebastian; Chu, Kaiqin; Dou, Hu; Smith, Zachary J

    2017-09-05

    Anemia is a widespread public health problem with 1/4 ~1/3 of the world's population being affected. In Southeast Asia, Thalassemia trait (TT) and iron deficiency anemia (IDA) are the two most common anemia types and can have a serious impact on quality of life. IDA patients can be treated with iron supplementation, yet TT patients have diminished capacity to process iron. Therefore, distinguishing between types of anemia is essential for effective diagnosis and treatment. Here, we present two advances towards low-cost screening for anemia. First: a new red-cell-based index, Joint Indicator A, to discriminate between IDA, TT, and healthy children in a Chinese population. We collected retrospective data from 384 Chinese children and used discriminant function analysis to determine the best analytic function to separate healthy and diseased groups, achieving 94% sensitivity and 90% specificity, significantly higher than reported indices. This result is achieved using only three red cell parameters: mean cell volume (MCV), red cell distribution width (RDW) and mean cell hemoglobin concentration (MCHC). Our second advance: the development of a low cost, portable red cell analyzer to measure these parameters. Taken together, these two results may help pave the way for widespread screening for nutritional and genetic anemias.

  18. Data on how several physiological parameters of stored red blood cells are similar in glucose 6-phosphate dehydrogenase deficient and sufficient donors

    Directory of Open Access Journals (Sweden)

    Vassilis L. Tzounakas

    2016-09-01

    Full Text Available This article contains data on the variation in several physiological parameters of red blood cells (RBCs donated by eligible glucose-6-phosphate dehydrogenase (G6PD deficient donors during storage in standard blood bank conditions compared to control, G6PD sufficient (G6PD+ cells. Intracellular reactive oxygen species (ROS generation, cell fragility and membrane exovesiculation were measured in RBCs throughout the storage period, with or without stimulation by oxidants, supplementation of N-acetylcysteine and energy depletion, following incubation of stored cells for 24 h at 37 °C. Apart from cell characteristics, the total or uric acid-dependent antioxidant capacity of the supernatant in addition to extracellular potassium concentration was determined in RBC units. Finally, procoagulant activity and protein carbonylation levels were measured in the microparticles population. Further information can be found in “Glucose 6-phosphate dehydrogenase deficient subjects may be better “storers” than donors of red blood cells” [1].

  19. Serological and molecular identification of H Antigen deficiency and the physical and chemical functions of H deficient red blood cells%红细胞H抗原缺陷型鉴定及其理化功能研究

    Institute of Scientific and Technical Information of China (English)

    何子毅; 邹文涛; 胡应明; 钟炽辉; 刘仁强; 王德文; 刘赴平

    2013-01-01

    Objective To study the serology, molecular biology, typing characteristics, and physical and chemical func-tions of H antigen-deficient red blood cells. Methods H antigen deficiency was identified by serological method,ABO and para- Bombay genotype was determined by SSP-PCR. Erythrocyte osmotic fragility test,and deformability test for H Antigen-deficient red blood cell were conducted. Cross matching tests, simulating blood recipient and donor,were also performed. Results A total of six blood donors were identified as H antigen-deficient by serological methods, among which 3 cases were h3 homozygous,one h4 homozygous,one h1h3 heterozygotes,and the last not determined. The osmotic fragility and the deformability of H antigen-deficient red blood cells were below those of H antigen normal cells. As a blood recipient, the major cross match showed stronger agglutination with A or B type RBCs, compared to O type RBCs. As a blood donor, the major cross match were negative with some recipients,and positive with others. Conclusion H antigen deficient RBCs do not react with anti-H,anti-H1/H can be detected in H deficient serum,ABO genes were normal. The osmotic fragility and the deformability of H antigen-deficient type RBCs were lower than those of H antigen normal cells. As a receipt,receiving 0 type blood,is safer than A type or B type blood. While as a donor,if cross match is non-reactive,H deficient RBCs could be transfused to 0 type recipient.%目的 研究红细胞H抗原缺陷型血清学及分子生物学分型特点及其理化功能.方法 采用血型血清学鉴定H抗原缺陷型、SSP-PCR进行ABO基因分型,采用红细胞渗透脆性试验、变形性试验检测H抗原缺陷型红细胞理化功能,模拟作为受血者或供血者进行交叉配血试验.结果 6名献血者血样经血清学方法确定为H抗原缺陷型,类孟买基因分型其中3例为h3纯合子,1例为h4纯合子,1例为h1h3杂合子,1例基因分型不确定;H抗原缺陷型红

  20. Evaluation of Platelet and Red Blood Cell Parameters with Proposal of Modified Score as Discriminating Guide for Iron Deficiency Anemia and β-Thalassemia Minor

    Science.gov (United States)

    Shrivastava, Vikas; Chandra, Smita; Rawat, Anil; Nautiyal, Ruchira

    2016-01-01

    Introduction Iron Deficiency Anaemia (IDA) and β-Thalassaemia Minor (BTM) are considered to be important cause of microcytic hypochromic anaemia. Studies have evaluated various red cell parameters which are easily available on electronic cell counters for discrimination of IDA and BTM in different ethnic populations. The analysis of previously established red cell discriminative indices with new cut-off have also been done by studies which may be relevant in their set of population for differentiation. Aim The study was conducted to propose a modified score considering the established red blood cell indices with a new cut off and to formulate index taking into consideration Red Blood Cell (RBC) and platelet parameters for early differentiation of IDA and BTM. Materials and Methods The prospective study included cases with MCV< 80 fl and new modified score of 11 was proposed by statistically analysing the previous discriminative indices with new cut-off by giving score 0 for IDA and score 1 for BTM. The summation of all scores gave modified 11 T score. A new cut off for differentiation of IDA and BTM was proposed in the study by using ROC curve and analysing AUC which statistically corresponded to highest accuracy. An attempt to formulate a new index using the RBC and platelet parameters was also made for initial discrimination. Results The study included 153 cases and in addition to red blood cell parameters, mean platelet volume and platelet distribution width also showed statistical significant difference between IDA and BTM (p<0.05). Modified new 11 T score was 87.6% specific for BTM while proposed index showed 80.4% negative predictive value for BTM and correctly identified 75% of cases. Conclusion The proposed new index and modified 11T score may be used for initial discrimination of BTM and IDA especially in resource limited regions. Apart from RBC parameters, mean platelet volume and platelet distribution width may also be useful in early differentiation

  1. High Red Blood Cell Count

    Science.gov (United States)

    Symptoms High red blood cell count By Mayo Clinic Staff A high red blood cell count is an increase in oxygen-carrying cells in your bloodstream. Red blood cells transport oxygen from your lungs to tissues throughout ...

  2. EVALUATION OF RED CELL INDICES AND RETICULOCYTE MATURITY INDICES INCLUDING RETICULOCYTE HAEMOGLOBIN CONCENTRATION IN IRON DEFICIENCY ANAEMIA IN ADULT FEMALE POPULATION

    Directory of Open Access Journals (Sweden)

    Anitha Sunkara

    2016-12-01

    Full Text Available BACKGROUND Prevalence of iron deficiency anaemia is higher in both developed, underdeveloped countries and in developing countries particularly in toddlers, adolescent girls and women of childbearing age. Diagnosis of iron deficiency is made by biochemical investigations along with the routine haemogram. Automated analysers in the recent years provide many reticulocyte parameters like Low Fluorescence Ratio (LFR, Medium Fluorescence Ratio (MFR and High Fluorescence Ratio (HFR, Reticulocyte Haemoglobin Concentration-haemoglobin (Ret-He, which not only aid in the diagnosis of Iron Deficiency Anaemia (IDA without the necessity of biochemical investigations, but also help in the follow up of these patients for bone marrow response accurately. The aim of the present study is to evaluate the effectiveness of these parameters in the diagnosis of iron deficiency anaemia in the female population in reproductive age group. MATERIALS AND METHODS The present study included peripheral blood samples from fifty eight women aged between 18-45 years from routine workload including 20 normal (Hb >12.0 g/dL with normal serum ferritin and serum iron levels and 38 iron deficiency anaemia samples (Hb <12.0 g/dL and with low serum ferritin and serum iron levels. RESULTS There was significant differences in the means between the subjects from the control group and IDA group in red cell distribution width, RDW CV (% (13.26±1.07 vs. 18.22±3.34 p-value <0.00001 and immature reticulocyte fraction (% (9.87±5.68 vs. 17.89±9.00 p-value=.000646, reticulocyte haemoglobin concentration (pg (33.34±2.92 vs. 22.0±4.13, p-value=<0.00001. Serum iron and serum ferritin showed statistically significant difference between two groups. CONCLUSIONS The reticulocyte parameters including Ret-He provide an important information in suspected cases of iron deficiency. Routine haemogram can thus be more helpful not only on morphological categorisation of anaemia, but also in knowing the

  3. The Value of Erythrocyte Indices and Red Cell Volume Distribution Width in Differential Diagnosis of Iron Deficiency Anemia and Anemia of Chronic Disease

    Directory of Open Access Journals (Sweden)

    Abdullah Altıntaş

    2007-01-01

    Full Text Available Iron deficiency anemia (IDA and anemia of chronic disease are the most commonly confused anemias. We investigate the diagnostic value of erythrocyte indices, red cell volume distribution width, and serum ferritin levels to make differential diagnosis of anemia in controls and anemic patients.Iron deficiency anemia (44 patients, anemia of chronic disease (41, IDA with anemia of chronic disease (17 and control (50 groups were compared. We performed serum ferritin, CBC, and sedimentation rate in all patientsand bone marrow aspiration in patients with anemia of chronic disease.Although mean cell volume (MCV and mean corpuscular hemoglobin (MCH are low in IDA and anemia of chronic disease, it is much striking in the former one (p<0.001, p<0.001. Only 7.3% of patients with anemia of chronic disease had a MCV<70 fL and MCH<24 pg, 90.0% of patients with IDA were below that cut-off point. Serum ferritin means were in patients with IDA and anemia of chronic disease were 4.6±3.3 and 489.6 ±519.9 ng/ml, respectively.The probability of IDA is low when RDW is normal in microcytic anemias. RDW is high in half of patients with anemia of chronic disease. Reference values for ferritin must be changed in patients with anemia of chronic disease and IDA. If serum ferritin is 57.6-146.4 ng/ml anemia of chronic disease and iron deficiency must ruled out by other diagnostic tests.

  4. Stability and reproducibility of ADVIA 120-measured red blood cell and platelet parameters in dogs, cats, and horses, and the use of reticulocyte haemoglobin content (CH(R)) in the diagnosis of iron deficiency

    NARCIS (Netherlands)

    Prins, M.; van Leeuwen, M.W.; Teske, E.

    2009-01-01

    Tijdschr Diergeneeskd. 2009 Apr 1;134(7):272-8. Stability and reproducibility of ADVIA 120-measured red blood cell and platelet parameters in dogs, cats, and horses, and the use of reticulocyte haemoglobin content (CH(R)) in the diagnosis of iron deficiency. Prins M, van Leeuwen MW, Teske E. Departm

  5. Diverse captive non-human primates with phytanic acid-deficient diets rich in plant products have substantial phytanic acid levels in their red blood cells

    Directory of Open Access Journals (Sweden)

    Moser Ann B

    2013-02-01

    Full Text Available Abstract Background Humans and rodents with impaired phytanic acid (PA metabolism can accumulate toxic stores of PA that have deleterious effects on multiple organ systems. Ruminants and certain fish obtain PA from the microbial degradation of dietary chlorophyll and/or through chlorophyll-derived precursors. In contrast, humans cannot derive PA from chlorophyll and instead normally obtain it only from meat, dairy, and fish products. Results Captive apes and Old world monkeys had significantly higher red blood cell (RBC PA levels relative to humans when all subjects were fed PA-deficient diets. Given the adverse health effects resulting from PA over accumulation, we investigated the molecular evolution of thirteen PA metabolism genes in apes, Old world monkeys, and New world monkeys. All non-human primate (NHP orthologs are predicted to encode full-length proteins with the marmoset Phyh gene containing a rare, but functional, GA splice donor dinucleotide. Acox2, Scp2, and Pecr sequences had amino acid positions with accelerated substitution rates while Amacr had significant variation in evolutionary rates in apes relative to other primates. Conclusions Unlike humans, diverse captive NHPs with PA-deficient diets rich in plant products have substantial RBC PA levels. The favored hypothesis is that NHPs can derive significant amounts of PA from the degradation of ingested chlorophyll through gut fermentation. If correct, this raises the possibility that RBC PA levels could serve as a biomarker for evaluating the digestive health of captive NHPs. Furthermore, the evolutionary rates of the several genes relevant to PA metabolism provide candidate genetic adaptations to NHP diets.

  6. Red blood cells, multiple sickle cells (image)

    Science.gov (United States)

    Sickle cell anemia is an inherited disorder in which abnormal hemoglobin (the red pigment inside red blood cells) is produced. The abnormal hemoglobin causes red blood cells to assume a sickle shape, like the ones seen in this photomicrograph.

  7. Rare red blood cell abnormalities

    NARCIS (Netherlands)

    van Zwieten, R.

    2015-01-01

    The aim of this thesis is to give insight in the process of diagnosing rare red blood cell defects, to clarify the relation of a defect with cell function and to extend, in this respect, our knowledge about normal red cell function and biochemistry. It is possible to categorize different red cell ab

  8. Acquired hemoglobin variants and exposure to glucose-6-phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen-matched blood.

    Science.gov (United States)

    Raciti, Patricia M; Francis, Richard O; Spitalnik, Patrice F; Schwartz, Joseph; Jhang, Jeffrey S

    2013-08-01

    Red blood cell exchange (RBCEx) is frequently used in the management of patients with sickle cell disease (SCD) and acute chest syndrome or stroke, or to maintain target hemoglobin S (HbS) levels. In these settings, RBCEx is a category I or II recommendation according to guidelines on the use of therapeutic apheresis published by the American Society for Apheresis. Matching donor red blood cells (RBCs) to recipient phenotypes (e.g., C, E, K-antigen negative) can decrease the risk of alloimmunization in patients with multi-transfused SCD. However, this may select for donors with a higher prevalence of RBC disorders for which screening is not performed. This report describes a patient with SCD treated with RBCEx using five units negative for C, E, K, Fya, Fyb (prospectively matched), four of which were from donors with hemoglobin variants and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Pre-RBCEx HbS quantification by high performance liquid chromatography (HPLC) demonstrated 49.3% HbS and 2.8% hemoglobin C, presumably from transfusion of a hemoglobin C-containing RBC unit during a previous RBCEx. Post-RBCEx HPLC showed the appearance of hemoglobin G-Philadelphia. Two units were G6PD-deficient. The patient did well, but the consequences of transfusing RBC units that are G6PD-deficient and contain hemoglobin variants are unknown. Additional studies are needed to investigate effects on storage, in-vivo RBC recovery and survival, and physiological effects following transfusion of these units. Post-RBCEx HPLC can monitor RBCEx efficiency and detect the presence of abnormal transfused units.

  9. Red Blood Cell Antibody Identification

    Science.gov (United States)

    ... ID, RBC; RBC Ab ID Formal name: Red Blood Cell Antibody Identification Related tests: Direct Antiglobulin Test ; RBC ... I should know? How is it used? Red blood cell (RBC) antibody identification is used as a follow- ...

  10. Red blood cells, sickle cell (image)

    Science.gov (United States)

    Sickle cell anemia is an inherited blood disease in which the red blood cells produce abnormal pigment (hemoglobin). ... abnormal hemoglobin causes deformity of the red blood cells into crescent or sickle-shapes, as seen in this photomicrograph.

  11. RELATIONSHIP BETWEEN LIPID PEROXIDATION AND RED BLOOD CELL IMMUNE FUNCTION IN PATIENTS WITH SPLEEN DEFICIENCY%脾虚患者脂质过氧化和红细胞免疫功能关系

    Institute of Scientific and Technical Information of China (English)

    章梅; 邱根全; 夏天

    2001-01-01

    Objective:To explore the effect of lipid peroxidation on red blood cell immune function in patients with spleen deficiency.Method:By the methods of TBA and red blood cell-yeast mixed flower circle,the RBC-C3b receptor rate,malonyldialdehyde(MDA) of plasma and erythrocyte membrane in patients with spleen deficiency were determined respectively.Result:The red blood cell C3b receptor rate(RBC-C3bRR)and red blood cell immune compound(RBC-IC) were lowered,but the MDA content in plasma and erythrocyte membrane were increased respectively.The relative analysis suggested that there were relationship between the RBC-C3bRR and MAD content in plasma and erythrocyte membrane.Conclusion:The lipid peroxidation lesion of red blood cell membrane had a bad effect on RBC-C3bRR.%目的:探讨脾虚患者脂质过氧化对红细胞免疫功能的影响。方法:采用红细胞酵母菌混合花环法和硫代巴比妥酸(TBA)法检测脾虚患者红细胞膜C3b受体花环率(RBC-C3bRR)、血浆及红细胞膜丙二醛(MDA)水平。结果:脾虚患者RBC-C3bRR和红细胞膜免疫复合物花环率(RBC-ICR)明显降低,血浆MDA和红细胞膜MDA明显升高;RBC-C3bRR与血浆MDA、红细胞膜MDA呈负相关,其中红细胞膜MDA和RBC-C3bRR关系更为密切。结论:红细胞膜脂质过氧化损害对RBC-C3bRR有不利影响。

  12. Pediatric red cell disorders and pure red cell aplasia.

    Science.gov (United States)

    Perkins, Sherrie L

    2004-12-01

    Anemia in children may arise from a wide variety of pathogenetic mechanisms that include congenital and acquired disorders. Often the diagnostic considerations include disorders that are not seen commonly in adults and lifelong disorders that arise in children and persist throughout life. Consideration of diverse causes of anemia such as red cell membrane disorders, red cell enzymopathies, congenital dyserythropoietic anemias, congenital sideroblastic anemias, and hereditary pure red cell aplasia (Diamond-Blackfan anemia), as well as infectious causes such as parvovirus B19 infection, often is required when diagnosing anemia in an infant or young child. Knowledge of these entities that are important causes of anemia in the pediatric population, including clinical manifestations and laboratory workup, will aid in recognition of the specific disease entities and effective workup of pediatric red cell disorders.

  13. In vitro generated Rh(null) red cells recapitulate the in vivo deficiency: a model for rare blood group phenotypes and erythroid membrane disorders.

    Science.gov (United States)

    Cambot, Marie; Mazurier, Christelle; Canoui-Poitrine, Florence; Hebert, Nicolas; Picot, Julien; Clay, Denis; Picard, Véronique; Ripoche, Pierre; Douay, Luc; Dubart-Kupperschmitt, Anne; Cartron, Jean-Pierre

    2013-05-01

    Lentiviral modification combined with ex vivo erythroid differentiation was used to stably inhibit RhAG expression, a critical component of the Rh(rhesus) membrane complex defective in the Rh(null) syndrome. The cultured red cells generated recapitulate the major alterations of native Rh(null) cells regarding antigen expression, membrane deformability, and gas transport function, providing the proof of principle for their use as model of Rh(null) syndrome and to investigate Rh complex biogenesis in human primary erythroid cells. Using this model, we were able to reveal for the first time that RhAG extinction alone is sufficient to explain ICAM-4 and CD47 loss observed on native Rh(null) RBCs. Together with the effects of RhAG forced expression in Rh(null) progenitors, this strongly strengthens the hypothesis that RhAG is critical to Rh complex formation. The strategy is also promising for diagnosis purpose in order to overcome the supply from rare blood donors and is applicable to other erythroid defects and rare phenotypes, providing models to dissect membrane biogenesis of multicomplex proteins in erythroid cells, with potential clinical applications in transfusion medicine.

  14. Disorders of red cell membrane

    National Research Council Canada - National Science Library

    An, Xiuli; Mohandas, Narla

    2008-01-01

    Summary Studies during the last three decades have enabled the development of detailed molecular insights into the structural basis of altered function in various inherited red cell membrane disorders...

  15. Red blood cells, spherocytosis (image)

    Science.gov (United States)

    Spherocytosis is a hereditary disorder of the red blood cells (RBCs), which may be associated with a mild anemia. Typically, the affected RBCs are small, spherically shaped, and lack the light centers seen ...

  16. Nitric Oxide Scavenging by Red Cell Microparticles

    OpenAIRE

    Liu, Chen; Zhao, Weixin; George J Christ; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

    2013-01-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the import...

  17. Red cell metabolism studies on Skylab

    Science.gov (United States)

    Mengel, C. E.

    1977-01-01

    Blood samples from Spacelab crewmembers were studied for possible environment effects on red cell components. Analysis involved peroxidation of red cell lipids, enzymes of red cell metabolism, and levels of 2,3-diphosphoglyceric acid and adenosine triphosphate. Results show that there is no evidence of lipid peroxidation, that biochemical effect known to be associated with irreversible red cell damage. Changes observed in glycolytic intermediates and enzymes cannot be directly implicated as indicating evidence of red cell damage.

  18. Red cell metabolism studies on Skylab

    Science.gov (United States)

    Mengel, C. E.

    1977-01-01

    Blood samples from Spacelab crewmembers were studied for possible environment effects on red cell components. Analysis involved peroxidation of red cell lipids, enzymes of red cell metabolism, and levels of 2,3-diphosphoglyceric acid and adenosine triphosphate. Results show that there is no evidence of lipid peroxidation, that biochemical effect known to be associated with irreversible red cell damage. Changes observed in glycolytic intermediates and enzymes cannot be directly implicated as indicating evidence of red cell damage.

  19. Red Cell Distribution Width

    Science.gov (United States)

    ... used to diagnose: Other blood disorders such as thalassemia , an inherited disease that can cause severe anemia ... cold hands and feet A family history of thalassemia, sickle cell anemia or other inherited blood disorder ...

  20. Characterization of Micronutrient Deficiency in Australian Red Cedar (Toona ciliata M. Roem var. australis

    Directory of Open Access Journals (Sweden)

    Bruno da Silva Moretti

    2012-01-01

    Full Text Available The Australian Red Cedar presents a great exploitation potential in Brazil, but works about the nutrient requirements and deficiency characterization in that species are still scarce. The objectives of this work were evaluating the effects of the omission of micronutrients and characterizing the nutrient deficiency symptoms in Australian Red Cedar saplings. The experiment was conducted in a greenhouse for a 90-day period. Australian Red Cedar cuttings were cultivated in pots with a nutrient solution under the missing element technique. The omission of the micronutrients B, Cu, Fe, Mn, and Zn affect negatively the height, diameter, and dry matter yield of the Australian Red Cedar plants. The micronutrient which affected the relative growth of the plants the most was B. Australian Red Cedar plants deficient in micronutrients present several visual symptoms characteristic of the metabolism disorders. The perception of the deficiencies through the visual diagnosis can be useful in the nutrient management of the culture of the Australian Red Cedar.

  1. First successful automated red cell exchange (erythrocytapheresis ...

    African Journals Online (AJOL)

    First successful automated red cell exchange (erythrocytapheresis) in ... PROMOTING ACCESS TO AFRICAN RESEARCH ... Hematopoietic Stem cell Transplantation (HSCT) remains the only curative therapy for Sickle Cell Disease (SCD).

  2. Red cell DAMPs and inflammation.

    Science.gov (United States)

    Mendonça, Rafaela; Silveira, Angélica A A; Conran, Nicola

    2016-09-01

    Intravascular hemolysis, or the destruction of red blood cells in the circulation, can occur in numerous diseases, including the acquired hemolytic anemias, sickle cell disease and β-thalassemia, as well as during some transfusion reactions, preeclampsia and infections, such as those caused by malaria or Clostridium perfringens. Hemolysis results in the release of large quantities of red cell damage-associated molecular patterns (DAMPs) into the circulation, which, if not neutralized by innate protective mechanisms, have the potential to activate multiple inflammatory pathways. One of the major red cell DAMPs, heme, is able to activate converging inflammatory pathways, such as toll-like receptor signaling, neutrophil extracellular trap formation and inflammasome formation, suggesting that this DAMP both activates and amplifies inflammation. Other potent DAMPs that may be released by the erythrocytes upon their rupture include heat shock proteins (Hsp), such as Hsp70, interleukin-33 and Adenosine 5' triphosphate. As such, hemolysis represents a major inflammatory mechanism that potentially contributes to the clinical manifestations that have been associated with the hemolytic diseases, such as pulmonary hypertension and leg ulcers, and likely plays a role in specific complications of sickle cell disease such as endothelial activation, vaso-occlusive processes and tissue injury.

  3. The IOC consensus statement: beyond the Female Athlete Triad--Relative Energy Deficiency in Sport (RED-S).

    Science.gov (United States)

    Mountjoy, Margo; Sundgot-Borgen, Jorunn; Burke, Louise; Carter, Susan; Constantini, Naama; Lebrun, Constance; Meyer, Nanna; Sherman, Roberta; Steffen, Kathrin; Budgett, Richard; Ljungqvist, Arne

    2014-04-01

    Protecting the health of the athlete is a goal of the International Olympic Committee (IOC). The IOC convened an expert panel to update the 2005 IOC Consensus Statement on the Female Athlete Triad. This Consensus Statement replaces the previous and provides guidelines to guide risk assessment, treatment and return-to-play decisions. The IOC expert working group introduces a broader, more comprehensive term for the condition previously known as 'Female Athlete Triad'. The term 'Relative Energy Deficiency in Sport' (RED-S), points to the complexity involved and the fact that male athletes are also affected. The syndrome of RED-S refers to impaired physiological function including, but not limited to, metabolic rate, menstrual function, bone health, immunity, protein synthesis, cardiovascular health caused by relative energy deficiency. The cause of this syndrome is energy deficiency relative to the balance between dietary energy intake and energy expenditure required for health and activities of daily living, growth and sporting activities. Psychological consequences can either precede RED-S or be the result of RED-S. The clinical phenomenon is not a 'triad' of the three entities of energy availability, menstrual function and bone health, but rather a syndrome that affects many aspects of physiological function, health and athletic performance. This Consensus Statement also recommends practical clinical models for the management of affected athletes. The 'Sport Risk Assessment and Return to Play Model' categorises the syndrome into three groups and translates these classifications into clinical recommendations.

  4. Nitric oxide scavenging by red cell microparticles.

    Science.gov (United States)

    Liu, Chen; Zhao, Weixin; Christ, George J; Gladwin, Mark T; Kim-Shapiro, Daniel B

    2013-12-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about 1000 times faster than red-cell-encapsulated hemoglobin. The degree to which this fast reaction with NO by red cell microparticles influences NO bioavailability depends on several factors that are explored here. In the context of stored blood preserved in ADSOL, we find that both cell-free hemoglobin and red cell microparticles increase as a function of duration of storage, and the proportion of extra erythrocytic hemoglobin in the red cell microparticle fraction is about 20% throughout storage. Normalized by hemoglobin concentration, the NO-scavenging ability of cell-free hemoglobin is slightly higher than that of red cell microparticles as determined by a chemiluminescence NO-scavenging assay. Computational simulations show that the degree to which red cell microparticles scavenge NO will depend substantially on whether they enter the cell-free zone next to the endothelial cells. Single-microvessel myography experiments performed under laminar flow conditions demonstrate that microparticles significantly enter the cell-free zone and inhibit acetylcholine, endothelial-dependent, and NO-dependent vasodilation. Taken together, these data suggest that as little as 5 μM hemoglobin in red cell microparticles, an amount formed after the infusion of one unit of aged stored packed red blood cells, has the potential to reduce NO bioavailability and impair endothelial-dependent vasodilation.

  5. Is red meat required for the prevention of iron deficiency among children and adolescents?

    Science.gov (United States)

    Savva, Savvas C; Kafatos, Anthony

    2014-01-01

    Iron deficiency remains the most common nutritional deficiency worldwide despite the fact that global prevention is a high priority. Recent guidelines suggest intake of red meat both in infants and toddlers to prevent iron deficiency. However frequent consumption of red and processed meat may be associated with an increased risk for cancer, cardiovascular disease and diabetes. Evidence also suggests that even in vegetarian diets or diets with little consumption of white or red meat, iron status may not be adversely affected. The Eastern Orthodox Christian Church dietary recommendations which is a type of periodic vegetarian diet, has proved beneficial for the prevention of iron deficiency and avoidance of excess iron intake. This paper aims to provide examples of meals for children and adolescents that may be sufficient to meet age specific iron requirements without consumption of red meat beyond the recommended consumption which is once or twice per month.

  6. Pure red cell aplasia and associated thymoma

    Directory of Open Access Journals (Sweden)

    Cristian Rosu

    2011-04-01

    Full Text Available Pure red cell aplasia is a rare cause of anemia, caused by an absence of red blood cell precursors in the bone marrow. It is usually a paraneoplastic syndrome, associated most commonly with large-cell granular lymphocyte leukemia but also thymoma. For patients who present both pure red cell aplasia and thymoma, thymectomy leads to an initial remission of the aplasia in 30% of cases. However, sustained remission may require the addition of medications such as corticosteroids, cyclospo­rine, or cyclophosphamide. We present a case of pure red cell aplasia associated with a thymoma in an otherwise healthy 80 year-old woman.

  7. Red cell or serum folate: what to do in clinical practice?

    Science.gov (United States)

    Farrell, Christopher-John L; Kirsch, Susanne H; Herrmann, Markus

    2013-03-01

    Folate deficiency has been linked to diverse clinical manifestations and despite the importance of accurate assessment of folate status, the best test for routine use is uncertain. Both serum and red cell folate assays are widely available in clinical laboratories; however, red cell folate is the more time-consuming and costly test. This review sought to evaluate whether the red cell assay demonstrated superior performance characteristics to justify these disadvantages. Red cell folate, but not serum folate, measurements demonstrated analytical variation due to sample pre-treatment parameters, oxygen saturation of haemoglobin and haematocrit. Neither marker was clearly superior in characterising deficiency but serum folate more frequently showed the higher correlation with homocysteine, a sensitive marker of deficiency. Similarly, both serum and red cell folate were shown to increase in response to folic acid supplementation. However, serum folate generally gave the greater response and was able to distinguish different supplementation doses. The C677T polymorphism of methylenetetrahydrofolate reductase alters the distribution of folate forms in red cells and may thereby cause further analytical variability in routine red cell folate assays. Overall, serum folate is cheaper and faster to perform than red cell folate, is influenced by fewer analytical variables and provides an assessment of folate status that may be superior to red cell folate.

  8. EVALUATION OF ANAEMIA USING RED CELL AND RETICULOCYTE PARAMETERS USING AUTOMATED HAEMATOLOGY ANALYSER

    Directory of Open Access Journals (Sweden)

    Vidyadhar Rao

    2016-06-01

    Full Text Available Use of current models of Automated Haematology Analysers help in calculating the haemoglobin contents of the mature Red cells, Reticulocytes and percentages of Microcytic and hypochromic Red cells. This has helped the clinician in reaching early diagnosis and management of Different haemopoietic disorders like Iron Deficiency Anaemia, Thalassaemia and anaemia of chronic diseases. AIM This study is conducted using an Automated Haematology Analyser to evaluate anaemia using the Red Cell and Reticulocyte parameters. Three types of anaemia were evaluated; iron deficiency anaemia, anaemia of long duration and anaemia associated with chronic disease and Iron deficiency. MATERIALS AND METHODS The blood samples were collected from 287 adult patients with anaemia differentiated depending upon their iron status, haemoglobinopathies and inflammatory activity. Iron deficiency anaemia (n=132, anaemia of long duration (ACD, (n=97 and anaemia associated with chronic disease with iron deficiency (ACD Combi, (n=58. Microcytic Red cells, hypochromic red cells percentage and levels of haemoglobin in reticulocytes and matured RBCs were calculated. The accuracy of the parameters was analysed using receiver operating characteristic analyser to differentiate between the types of anaemia. OBSERVATIONS AND RESULTS There was no difference in parameters between the iron deficiency group or anaemia associated with chronic disease and iron deficiency. The hypochromic red cells percentage was the best parameter in differentiating anaemia of chronic disease with or without absolute iron deficiency with a sensitivity of 72.7% and a specificity of 70.4%. CONCLUSIONS The parameters of red cells and reticulocytes were of reasonably good indicators in differentiating the absolute iron deficiency anaemia with chronic disease.

  9. Stability and reproducibility of ADVIA 120-measured red blood cell and platelet parameters in dogs, cats, and horses, and the use of reticulocyte haemoglobin content (CH(R)) in the diagnosis of iron deficiency.

    Science.gov (United States)

    Prins, M; van Leeuwen, M W; Teske, E

    2009-04-01

    Modern laser-based haematology analysers such as the ADVIA 120 have species-specific software and offer the possibility of assessing new haematological parameters. These parameters have yet to be evaluated, and as these analysers are often used in referral laboratories, it is important to know whether the values of haematological parameters change during sample transport. Therefore, samples of EDTA-anticoagulated blood from nine healthy dogs and EDTA- and citrate-anticoagulated blood from six healthy horses were collected and stored at room temperature for 72 and 48 hours, respectively. In canine samples, WBC and the red blood cell parameters Hb, Hb(cell), Ht, MCV, and MCHC changed significantly after only 24 hours of storage. Thus if canine blood samples need to be stored for 24 hours or longer, Hb, RBC, and MCH would appear to be more reliable parameters than Ht, Hb(cell), MCV, and MCHC. The cytoplasmic haemoglobin content (CH(R)) remained stable up to 48 hours. Both dog and horse platelet numbers were stable over time when blood was anticoagulated with EDTA. Of the platelet-derived parameters, MPC was already significantly lower 2 hours after collection of equine blood samples and was also significantly lower 24 hours after collection of canine blood samples. In contrast, MPV levels were significantly higher 48 hours after sample collection. Initial platelet numbers and platelet parameters were significantly different in citrate-anticoagulated blood and EDTA-anticoagulated blood, and platelet numbers and MPM decreased significantly in citrate-anticoagulated blood samples after only 4 hours of storage. After reference intervals for CH(R) had been established using samples from 53 non-anaemic dogs and 150 non-anaemic cats, the use of CH(R) to detect iron deficiency anaemia was tested in 63 dogs and 55 cats with different diseases. With the help of ROC curves, the optimal cut-off point was determined to be 1.22 fmol in dogs and 0.88 fmol in cats, resulting in a

  10. Inflight Assay of Red Blood Cell Deformability

    Science.gov (United States)

    Ingram, M.; Paglia, D. E.; Eckstein, E. C.; Frazer, R. E.

    1985-01-01

    Studies on Soviet and American astronauts have demonstrated that red blood cell production is altered in response to low gravity (g) environment. This is associated with changes in individual red cells including increased mean cell volume and altered membrane deformability. During long orbital missions, there is a tendency for the red cell mass deficit to be at least partly corrected although the cell shape anomalies are not. Data currently available suggest that the observed decrease in red cell mass is the result of sudden suppression of erythropoieses and that the recovery trend observed during long missions reflects re-establishment of erythropoietic homeostasis at a "set point" for the red cell mass that is slightly below the normal level at 1 g.

  11. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... TV, Video Games, and the Internet Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia Print A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  12. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia A A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  13. Red blood cell alloimmunization after blood transfusion

    NARCIS (Netherlands)

    Schonewille, Henk

    2008-01-01

    Current pretransfusion policy requires the patients’ serum to be tested for the presence of irregular red blood cell antibodies. In case of an antibody, red blood cells lacking the corresponding antigen are transfused after an antiglobulin crossmatch. The aim of the studies in this thesis is primari

  14. Recovery of red fluorescent protein chromophore maturation deficiency through rational design.

    Directory of Open Access Journals (Sweden)

    Matthew M Moore

    Full Text Available Red fluorescent proteins (RFPs derived from organisms in the class Anthozoa have found widespread application as imaging tools in biological research. For most imaging experiments, RFPs that mature quickly to the red chromophore and produce little or no green chromophore are most useful. In this study, we used rational design to convert a yellow fluorescent mPlum mutant to a red-emitting RFP without reverting any of the mutations causing the maturation deficiency and without altering the red chromophore's covalent structure. We also created an optimized mPlum mutant (mPlum-E16P that matures almost exclusively to the red chromophore. Analysis of the structure/function relationships in these proteins revealed two structural characteristics that are important for efficient red chromophore maturation in DsRed-derived RFPs. The first is the presence of a lysine residue at position 70 that is able to interact directly with the chromophore. The second is an absence of non-bonding interactions limiting the conformational flexibility at the peptide backbone that is oxidized during red chromophore formation. Satisfying or improving these structural features in other maturation-deficient RFPs may result in RFPs with faster and more complete maturation to the red chromophore.

  15. Red blood cell decreases of microgravity

    Science.gov (United States)

    Johnson, P. C.

    1985-01-01

    Postflight decreases in red blood cell mass (RBCM) have regularly been recorded after exposure to microgravity. These 5-25 percent decreases do not relate to the mission duration, workload, caloric intake or to the type of spacecraft used. The decrease is accompanied by normal red cell survivals, increased ferritin levels, normal radioactive iron studies, and increases in mean red blood cell volume. Comparable decreases in red blood cell mass are not found after bed rest, a commonly used simulation of the microgravity state. Inhibited bone marrow erythropoiesis has not been proven to date, although reticulocyte numbers in the peripheral circulation are decreased about 50 percent. To date, the cause of the microgravity induced decreases in RBCM is unknown. Increased splenic trapping of circulating red blood cells seem the most logical way to explain the results obtained.

  16. Red cell membrane: past, present, and future

    National Research Council Canada - National Science Library

    Mohandas, Narla; Gallagher, Patrick G

    2008-01-01

    .... The non-nucleated red cell is unique among human cell type in that the plasma membrane, its only structural component, accounts for all of its diverse antigenic, transport, and mechanical characteristics...

  17. 21 CFR 640.10 - Red Blood Cells.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Red Blood Cells. 640.10 Section 640.10 Food and... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.10 Red Blood Cells. The proper name of this product shall be Red Blood Cells. The product is defined as red blood cells remaining...

  18. Red cell hemolysis during processing and storage

    Directory of Open Access Journals (Sweden)

    Sawant R

    2007-01-01

    Full Text Available Introduction: Apart from the visual assessment, measurement of plasma hemoglobin in the supernatant from red cell units provides an objective measure of the extent of hemolysis during storage. Study Design and Methods: Packed red cells (N=50, 25 units each in triple (CPD-A1 and SAGM and quadruple (CPD-A1 and ADSOL blood bags were evaluated for plasma hemoglobin by the tetramethylbenzidiene (TMB method on day 1, 7, 14, 21 and 28 of collection. The hemoglobin, hematocrit, MCV, LDH and potassium levels were also noted. Whole blood units (N=25 were used as controls. Results: Hemolysis increased in all the stored red cell units. Plasma hemoglobin increased significantly in the first week of storage. The hemolysis, LDH and potassium levels were found to be significantly higher in the red cell units harvested from the triple blood bags. However, on day 28 of storage, free hemoglobin in all the red cell units was much below the 0.8% hemolysis. Conclusion: Hemolysis of the red cells increases due to processing and during storage and is maximum during the first week. Adequate process control and proper storage facilities should be ensured to minimize the hemolysis of red cells during processing and storage.

  19. Human spleen and red blood cells

    Science.gov (United States)

    Pivkin, Igor; Peng, Zhangli; Karniadakis, George; Buffet, Pierre; Dao, Ming

    2016-11-01

    Spleen plays multiple roles in the human body. Among them is removal of old and altered red blood cells (RBCs), which is done by filtering cells through the endothelial slits, small micron-sized openings. There is currently no experimental technique available that allows us to observe RBC passage through the slits. It was previously noticed that people without a spleen have less deformable red blood cells, indicating that the spleen may play a role in defining the size and shape of red blood cells. We used detailed RBC model implemented within the Dissipative Particle Dynamics (DPD) simulation framework to study the filter function of the spleen. Our results demonstrate that spleen indeed plays major role in defining the size and shape of the healthy human red blood cells.

  20. Caspase 12 in calnexin-deficient cells.

    Science.gov (United States)

    Groenendyk, Jody; Zuppini, Anna; Shore, Gordon; Opas, Michal; Bleackley, R Chris; Michalak, Marek

    2006-11-07

    We investigated a role for calnexin, caspase 12, and Bap31 in endoplasmic reticulum stress-induced apoptosis in calnexin-deficient mouse embryonic fibroblasts and a calnexin-deficient human T cell line (NKR). We showed that calnexin-deficient mouse embryonic fibroblasts are relatively resistant to endoplasmic reticulum stress-induced apoptosis. Western blot analysis demonstrated that both wild-type and calnexin-deficient cells contained a caspase 12 protein. Caspase 12 expression was slightly inhibited in calnexin-deficient cells, and the protein carried out specific cleavage in the presence of thapsigargin. Immunoprecipitation experiments revealed that in the endoplasmic reticulum, caspase 12 forms complexes with Bap31 and calnexin. Treatment of wild-type cells with thapsigargin induced apoptosis and cleavage of Bap31. However, in the absence of calnexin, there was no significant cleavage of Bap31. There was also a negligible processing of caspase 8 in these cells. This work indicates that calnexin may play a role in modulating the sensitivity of a cell to apoptosis induced by endoplasmic reticulum stress, in conjunction with caspase 12 and Bap31.

  1. Malaria and human red blood cells.

    Science.gov (United States)

    Mohandas, Narla; An, Xiuli

    2012-11-01

    Invasion by the malaria parasite, Plasmodium falciparum, brings about extensive changes in the host red cells. These include loss of the normal discoid shape, increased rigidity of the membrane, elevated permeability to a wide variety of ionic and other species and increased adhesiveness, most notably to endothelial surfaces. These effects facilitate survival of the parasite within the host cell and tend to increase the virulence of disease that includes cerebral malaria and anemia. Numerous proteins secreted by the internalized parasite and interacting with red cell membrane proteins are responsible for the changes occurring to the host cell. Anemia, a serious clinical manifestation of malaria, is due to increased destruction of both infected and uninfected red cells due to membrane alterations, as well as ineffective erythropoiesis. There is very good evidence that various red cell disorders including hemoglobinopathies and hereditary ovalocytosis decrease the virulence of disease following parasite infection. A number of mechanism(s) are likely responsible for the protective effect of various red cell abnormalities including decreased invasion, impaired intraerythrocytic development of the parasites and altered interaction between exported parasite proteins and the red cell membrane skeleton.

  2. Folate-deficiency anemia

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000551.htm Folate-deficiency anemia To use the sharing features on this page, please enable JavaScript. Folate-deficiency anemia is a decrease in red blood cells (anemia) ...

  3. Red palm oil as an intervention food to prevent vitamin A deficiency.

    Science.gov (United States)

    Vitamin A deficiency (VAD) is an important cause of blindness. Red palm oil (RPO) is the richest food source of VA-forming carotenoids. We evaluated RPO carotenoid concentration and bioavailability, and used this data to estimate the amount of RPO needed to meet VA requirements. Amounts ranged fr...

  4. Utilization and quality of cryopreserved red blood cells in transfusion medicine.

    Science.gov (United States)

    Henkelman, S; Noorman, F; Badloe, J F; Lagerberg, J W M

    2015-02-01

    Cryopreserved (frozen) red blood cells have been used in transfusion medicine since the Vietnam war. The main method to freeze the red blood cells is by usage of glycerol. Although the usage of cryopreserved red blood cells was promising due to the prolonged storage time and the limited cellular deterioration at subzero temperatures, its usage have been hampered due to the more complex and labour intensive procedure and the limited shelf life of thawed products. Since the FDA approval of a closed (de) glycerolization procedure in 2002, allowing a prolonged postthaw storage of red blood cells up to 21 days at 2-6°C, cryopreserved red blood cells have become a more utilized blood product. Currently, cryopreserved red blood cells are mainly used in military operations and to stock red blood cells with rare phenotypes. Yet, cryopreserved red blood cells could also be useful to replenish temporary blood shortages, to prolong storage time before autologous transfusion and for IgA-deficient patients. This review describes the main methods to cryopreserve red blood cells, explores the quality of this blood product and highlights clinical settings in which cryopreserved red blood cells are or could be utilized.

  5. Diphenylhydantoin-induced pure red cell aplasia.

    Science.gov (United States)

    Rusia, Usha; Malhotra, Purnima; Joshi, Panul

    2006-01-01

    Pure red cell aplasia is an uncommon complication of diphenylhydantoin therapy. It has not been reported in Indian literature. Awareness of the entity helps in establishing the cause of anaemia in these patients and alerts the physicians to the need of comprehensive haematological monitoring in these patients. A case of 58-year-old male who developed pure red cell aplasia following three months of diphenylhydantoin therapy is reported here.

  6. Autoimmune Lymphoproliferative Syndrome with Red Cell Aplasia.

    Science.gov (United States)

    Meena, K R; Bisht, Supriya; Tamaria, K C

    2015-12-01

    Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of abnormal lymphocyte apoptosis, leading to chronic lymphoproliferation. It presents as lymphadenopathy, hepatosplenomegaly and autoimmune phenomena. Pure red cell aplasia is characterized by normochromic normocytic anemia, reticulocytopenia, and absence of erythroblasts from a normal bone marrow. Only few lymphoproliferative disorders have been associated with erythroid aplasia. The authors are reporting a case of ALPS associated with red cell aplasia in a 7-y-old girl.

  7. Hereditary red cell membrane disorders and laboratory diagnostic testing.

    Science.gov (United States)

    King, M-J; Zanella, A

    2013-06-01

    This overview describes two groups of nonimmune hereditary hemolytic anemias caused by defects in membrane proteins located in distinct layers of the red cell membrane. Hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP) represent disorders of the red cell cytoskeleton. Hereditary stomatocytoses represents disorders of cation permeability in the red cell membrane. The current laboratory screening tests for HS are the osmotic fragility test, acid glycerol lysis time test (AGLT), cryohemolysis test, and eosin-5'-maleimide (EMA)-binding test. For atypical HS, SDS-polyacrylamide gel electrophoresis of erythrocyte membrane proteins is carried out to confirm the diagnosis. The diagnosis of HE/HPP is based on abnormal red cell morphology and the detection of protein 4.1R deficiency or spectrin variants using gel electrophoresis. None of screening tests can detect all HS cases. Some testing centers (a survey of 25 laboratories) use a combination of tests (e.g., AGLT and EMA). No specific screening test for hereditary stomatocytoses is available. The preliminary diagnosis is based on presenting a compensated hemolytic anemia, macrocytosis, and a temperature or time dependent pseudohyperkalemia in some patients. Both the EMA-binding test and the osmotic fragility test may help in differential diagnosis of HS and hereditary stomatocytosis.

  8. Phosphatidylserine exposure and red cell viability in red cell aging and in hemolytic anemia

    Science.gov (United States)

    Boas, Franz Edward; Forman, Linda; Beutler, Ernest

    1998-01-01

    Phosphatidylserine (PS) normally localizes to the inner leaflet of cell membranes but becomes exposed in abnormal or apoptotic cells, signaling macrophages to ingest them. Along similar lines, it seemed possible that the removal of red cells from circulation because of normal aging or in hemolytic anemias might be triggered by PS exposure. To investigate the role of PS exposure in normal red cell aging, we used N-hydroxysuccinimide-biotin to tag rabbit red cells in vivo, then used phycoerythrin-streptavidin to label the biotinylated cells, and annexin V-fluorescein isothiocyanate (FITC) to detect the exposed PS. Flow cytometric analysis of these cells drawn at 10-day intervals up to 70 days after biotinylation indicated that older, biotinylated cells expose more PS. Furthermore, our data match a simple model of red cell senescence that assumes both an age-dependent destruction of senescent red cells preceded by several hours of PS exposure and a random destruction of red cells without PS exposure. By using this model, we demonstrated that the exposure of PS parallels the rate at which biotinylated red cells are removed from circulation. On the other hand, using an annexin V-FITC label and flow cytometry demonstrates that exposed PS does not cause the reduced red cell life span of patients with hemolytic anemia, with the possible exception of those with unstable hemoglobins or sickle cell anemia. Thus, in some cases PS exposure on the cell surface may signal the removal of red cells from circulation, but in other cases some other signal must trigger the sequestration of cells. PMID:9501218

  9. Red cell parameters in infant and children from the Arabian Peninsula.

    Science.gov (United States)

    Mekaini, Lolowa A Al; Denic, Srdjan; Jabri, Omar N Al; Narchi, Hassib; Souid, Abdul-Kader; Al-Hammadi, Suleiman

    2015-01-01

    α+-Thalassemia trait and iron deficiency anemia are frequent causes of microcytosis and a common diagnostic challenge in Arabian children. In this study, their prevalences and effects on the red cell parameters were evaluated in 28,457 children aged one day to 6 years. α+-Thalassemia trait was considered to be present when mean cell volume (MCV) was iron deficiency anemia when red cell distribution width (RDW) was >14.5%. The prevalence of α+-thalassemia trait was 15.7% (502/3,191), which was similar to previously reported values for adults (9-14%). Iron deficiency anemia peaked at 7 months (53%) and then declined at a rate of 8% per year. The nadirs of red blood cell count (RBC) and hemoglobin concentration (Hb) occurred at two months of age (physiological anemia). Subsequently, Hb increased at a rate similar to that of MCV, demonstrating the two processes are coupled. The third percentile MCV in children older than 3 months was ≤64 fL, which was significantly lower than that in European children. The third percentile Hb, on the other hand, was similar to that in European children. Thus, α+-thalassemia trait and iron deficiency anemia are exceptionally frequent in Arabian children and their red cell indices are considerably different from European-based norms. Careful interpretation of red cell parameters is required for the evaluation of microcytic anemia in Arabian children.

  10. 21 CFR 864.8540 - Red cell lysing reagent.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Red cell lysing reagent. 864.8540 Section 864.8540...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8540 Red cell lysing reagent. (a) Identification. A red cell lysing reagent is a device used to lyse (destroy) red blood cells...

  11. 21 CFR 864.5300 - Red cell indices device.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Red cell indices device. 864.5300 Section 864.5300....5300 Red cell indices device. (a) Identification. A red cell indices device, usually part of a larger... corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC). The red cell...

  12. Clinical study on the role of red blood cells and reticulocyte parameters in identification of light β-mediterranean anemia and iron deficiency anemia%红细胞及网织红细胞参数在轻型β地贫与缺铁贫鉴别临床研究

    Institute of Scientific and Technical Information of China (English)

    柯宗明

    2013-01-01

    目的 探讨血常规红细胞参数及网织红细胞参数在轻型β地中海贫血和缺铁性贫血的临床鉴别诊断中的应用价值.方法 将98例缺铁性贫血患者设为缺铁贫组,46例轻型β地中海贫血设为地贫组,44例正常体检人员设为对照组.比较3组血常规红细胞参数及网织红细胞参数水平.结果 红细胞参数方面,缺铁贫组、地贫组MCV、MCH、MCHC出现降低,与对照组比较有显著差异(P<0.05);缺铁贫组RDW升高,地贫组RDW与对照组比较无显著差异(P>0.05);网织红细胞参数方面,缺铁贫组、地贫组RET#、RET%、IRF、MFR%、HFR%均出现升高,LFR%出现降低,且地贫组变化更为显著;缺铁贫组Ret-He出现降低,与地贫组、对照组比较均有显著差异(P<0.05),而地贫组与对照组比较无显著差异(P>0.05).结论 红细胞及网织红细胞参数在轻型β地中海贫血和缺铁性贫血的临床鉴别诊断中具有重要的意义.%Objective To study the application value of red blood cells and reticulocyte parameters in the clinical identification of light β-mediterranean anemia and iron deficiency anemia.Methods Ninety-eight patients with iron deficiency anemia were set to iron deficiency anemia group,forty-six patients of light β-mediterranean were set to the mediterranean anemia group,and forty-four health subjects were set to the control group.A comparison was made between groups in terms of routine blood red blood cell parameters and the characteristics of reticulocyte parameters.Results Erythrocyte parameters such as MCV,MCH and MCHC in iron deficiency anemia group and Mediterranean anemia group decreased.Compared with the control group,the differences were statistically significant (P < 0.05).RDW in iron deficiency anemia group increased.Compared with the Mediterranean anemia group,the differences in RDW showed no significant difference (P >0.05).As for the reticulocyte parameters

  13. Genomic Typing of Red Cell Antigens

    Science.gov (United States)

    2011-09-01

    Antigen‐Matched  Red  Cells  for  Sickle  Cell  Anemia   Patients  Using  Molecular Typing to Augment Testing: Meghan Delaney, Prashant Gaur, Askale...Antigen‐Matched Red Cells for Sickle Cell  Anemia  Patients  Using Molecular Typing to Augment Testing: AABB (poster) 2009.  Background: Patients with sickle...not used. Delivery of a  healthy female  neonate  was uneventful. The serologic studies showed the mother and baby’s  phenotypes as O and AB

  14. Red cells and rouleaux in shear flow.

    Science.gov (United States)

    Goldsmith, H L

    1966-09-16

    The rotation and deformation of human red cells and linear aggregates (rouleaux) in dilute plasma suspension were observed in Poiseuille and Couette flow. Single lunideform-led erythrocyte. s and roluleauix rotated in orbits predicted by theory for rigid spheroids. Bending of rouleaux occurred at orientations at which compressive forces act on the particles and the degree of flexibility increased with the number of cells in linear array.

  15. Enzyme-inhibitor mediated red cell labelling

    Energy Technology Data Exchange (ETDEWEB)

    Ackery, D.M.; Singh, J.; Wyeth, P. (Southampton Univ. (UK). Dept. of Chemistry)

    Red blood cells contain 90% of the body's enzyme carbonic anhydrase to which aromatic sulphonamide inhibitors bind tightly. P-iodo-benzene sulphonamide (PIBS) is a lipophilic inhibitor which would afford rapid cell labelling. Radioiodinated PIBS was prepared, in high yield, by radio ion exchange in the presence of ammonium sulphate. After intravenous injection of /sup 131/I-PIBS the radiolabel was found in the blood pool.

  16. Single-cell measurement of red blood cell oxygen affinity

    CERN Document Server

    Caprio, Di; Higgins, John M; Schonbrun, Ethan

    2015-01-01

    Oxygen is transported throughout the body by hemoglobin in red blood cells. While the oxygen affinity of blood is well understood and is routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of red blood cell volume and hemoglobin concentration are taken millions of times per day by clinical hematology analyzers and are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume and hemoglobin concentration for individual red blood cells in high-throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.5%, which corresponds to the maximum slope of the oxygen-hemoglobin dissociation curve. In addition, single-cell oxygen affinity is positively correlated with hemoglobin concentr...

  17. Pure Red Cell Aplasia Caused by Acute Hepatitis A

    OpenAIRE

    Lee, Tae Heon; Oh, Suk Joong; Hong, Soojung; Lee, Kyu Bek; Park, Hyosoon; Woo, Hee-Yeon

    2011-01-01

    Pure red cell aplasia is characterized as a normocytic anemia associated with reticulocytopenia and the absence of erythroblasts in the bone marrow. Pure red cell aplasia can be induced by various causes such as thymoma, connective tissue disease, viral infection, lymphoma, and adverse drug reactions. There have been only a few reports of pure red cell aplasia associated with acute viral hepatitis A. In Korea, no case of pure red cell aplasia caused by acute hepatitis A has yet been reported....

  18. Risk of Abnormal Red Blood Cell to Get Malarial Infection

    OpenAIRE

    Viroj Wiwanitkit

    2008-01-01

    Malarial infection in red blood cell disorder is an interesting topic in tropical medicine. In this work, the author proposes a new idea on the physical property of red blood cell and risk for getting malarial infection. The study on scenario of red blood cell disorders is performed. Conclusively, the author found that physical property of red blood cell is an important determinant for getting malarial infection

  19. 21 CFR 864.8185 - Calibrator for red cell and white cell counting.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Calibrator for red cell and white cell counting... Calibrator for red cell and white cell counting. (a) Identification. A calibrator for red cell and white cell counting is a device that resembles red or white blood cells and that is used to set instruments...

  20. 21 CFR 660.30 - Reagent Red Blood Cells.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reagent Red Blood Cells. 660.30 Section 660.30...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660.30 Reagent Red Blood Cells. (a) Proper name and definition. The proper name of the product shall be...

  1. 21 CFR 864.7100 - Red blood cell enzyme assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Red blood cell enzyme assay. 864.7100 Section 864...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7100 Red blood cell enzyme assay. (a) Identification. Red blood cell enzyme assay is a device used to measure the activity...

  2. Acquired pure red cell aplasia in children

    Directory of Open Access Journals (Sweden)

    Sujata R Dafale

    2012-01-01

    Full Text Available Acquired Pure Red Cell Aplasia (PRCA is a rare occurrence in children.This is a case of an eight year old girl child who developed acquired PRCA secondary to long term intake of sodium Valproate. This case is reported to review the causes of PRCA in children and to reconsider the use of drugs of longer duration in children and adults.

  3. Phenotypic and quantitative relationship of red cell acid phosphatase with haemoglobin, haptoglobin, and G6PD phenotypes.

    Science.gov (United States)

    Saha, N; Patgunarajah, N

    1981-08-01

    The phenotypic and quantitative relationship of red cell acid phosphatase with haemoglobin, haptoglobin, and G6PD phenotypes was investigated in three populations in the Sudan and one population in Nilgiris, India. No significant consistent association of red cell acid phosphatase phenotypes was observed with these polymorphisms. However, there was a lack of acid phosphatase AB in G6PD deficient subjects from Nilgiris. The relative quantitative expression of red cell acid phosphatase genes PA, PB, and PC was 1.0, 1.2, and 1.3, respectively. The red cell acid phosphatase activity was higher (15%) in the presence of raised haemoglobin A2 and in sickle cell anaemia (21%). Those with Hp2 had 18% higher level of acid phosphatase than those with Hp1. G6PD deficient subjects had a lower level of acid phosphatase activity (20%) than those with normal G6PD activity.

  4. Neocytolysis: physiological down-regulator of red-cell mass

    Science.gov (United States)

    Alfrey, C. P.; Rice, L.; Udden, M. M.; Driscoll, T. B.

    1997-01-01

    It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.

  5. Neocytolysis: physiological down-regulator of red-cell mass

    Science.gov (United States)

    Alfrey, C. P.; Rice, L.; Udden, M. M.; Driscoll, T. B.

    1997-01-01

    It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.

  6. Anemia and iron deficiency in children: association with red meat and poultry consumption.

    Science.gov (United States)

    Moshe, Galit; Amitai, Yona; Korchia, Gerard; Korchia, Levana; Tenenbaum, Ariel; Rosenblum, Joseph; Schechter, Avi

    2013-12-01

    The aim of this study was to study the relative contribution of dietary sources of iron in children with high prevalence of anemia and iron deficiency (ID). A cross-sectional study in 263 healthy, 1.5- to 6-year-old children in the Jewish sector of Jerusalem, Israel. Venous blood samples and a qualitative Food Frequency Questionnaire on iron-rich foods were obtained. Anemia was defined as hemoglobin children younger than 4 years and children older than 4 years; ID was defined as ferritin iron-deficiency anemia in 3.7%. The prevalence of anemia was higher in toddlers ages 1.5 to 3 years compared with children ages 3 to 6 years (17.7% vs 7.3%, P = 0.01). Children with extremely low red meat consumption (seldom) had 4-fold higher rates of ID than those who consumed ≥2 times per week (odds ratio 3.98; 95% confidence interval 1.21-13.03; P = 0.023), whereas poultry consumption was not associated with ID. Soy consumption was inversely associated with ferritin (marginally significant, r = -0.134, P = 0.057). The high prevalence of anemia and ID found in this study, mainly in children 1.5 to 3 years old, is related to low red meat consumption. The characteristically high poultry consumption in the Israeli population was not protective. The shift toward reduced red meat consumption and higher poultry consumption in developed countries may result in increasing the risk of ID.

  7. In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong

  8. Prevalence of red-green color vision deficiency (cvd among science students: a 10 years' survey

    Directory of Open Access Journals (Sweden)

    Arun V. Panat , M.Sc. M.Phil.

    2016-02-01

    Full Text Available Red-green Color vision deficiency (CVD has a high prevalence and is often a handicap in everyday life. The fact that most of the students do not know they have CVD due to non testing of color vision. All Science faculty students of the ASC Rahuri College in the age range of 17-19 were screened for Red-green CVD by using Ishihara test plates from 2001 to 2010. Thus total 654 males and 292 female students were screened during 10 years. The collected data were analyzed for frequency estimation among males and females and then estimating mating types by using the Hardy-Weinberg Principle. Frequency of color blindness in males was 0.303 and that in females 0.288. Predicted mating types show a higher contribution of carrier females, and homozygous color blinds than expected. Estimated normal mating type is only 35.35%. Prevalence of Red-green CVD was found considerably high among science students and specifically among females which is unusual. Mating types involving carrier females, colorblind females, and colorblind males together show a very high contribution than normal ones.

  9. H-deficient Bombay and para-Bombay red blood cells are most strongly agglutinated by the galactophilic lectins of Aplysia and Pseudomonas aeruginosa that detect I and P1 antigens.

    Science.gov (United States)

    Gilboa-Garber, N; Sudakevitz, D; Levene, C; Rahimi-Levene, N; Yahalom, V

    2006-01-01

    The galactophilic lectins Aplysia gonad lectin (AGL) and Pseudomonas aeruginosa lectin (PA-IL), which detect human I and P1 RBC antigens, were examined for hemagglutination of H+ (group O and B) and H-deficient (Bombay and para-Bombay phenotype) RBCs. The results were compared with those obtained using two other galactophilic lectins, Maclura pomifera lectin (MPL) and Arachis hypogaea (peanut) agglutinin (PNA), which share T-antigen affinity, and two fucose-binding H-specific lectins, Ulex europaeus (UEA-I) and Pseudomonas aeruginosa lectin (PA-IIL), as well as with those achieved with anti-I serum. The results revealed that, in contrast to UEA-I and PA-IIL, which preferentially agglutinated H+ RBCs, and to MPL and PNA, which similarly agglutinated all examined RBCs, AGL, PA-IL, and the anti-I serum agglutinated the H-deficient RBCs more strongly than did the H+ RBCs. These findings could be attributed to increased levels of I and P1 antigens on those RBCs resulting from the use of the free common H-type 2 precursor for their synthesis. Since both PA-IL and PA-IIL are regarded as potential pathogen adhesins, it would be interesting to statistically compare the sensitivities of individuals of H+ and H-deficient RBC populations to P. aeruginosa infections.

  10. Low red cell production may protect against severe anemia during a malaria infection – insights from modeling

    OpenAIRE

    Cromer, Deborah; Stark, Jaroslav; P Davenport, Miles

    2009-01-01

    Abstract The malaria parasite causes lysis of red blood cells, resulting in anemia, a major cause of mortality and morbidity. Intuitively, one would expect the production of red blood cells to increase in order to compensate for this loss. However, it has been observed that this response is weaker than would be expected. Furthermore iron supplementation for iron deficient children in malaria endemic regions can paradoxically adversely affect the clinical outcome of malaria infectio...

  11. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders.

    Science.gov (United States)

    Da Costa, Lydie; Galimand, Julie; Fenneteau, Odile; Mohandas, Narla

    2013-07-01

    Hereditary spherocytosis and elliptocytosis are the two most common inherited red cell membrane disorders resulting from mutations in genes encoding various red cell membrane and skeletal proteins. Red cell membrane, a composite structure composed of lipid bilayer linked to spectrin-based membrane skeleton is responsible for the unique features of flexibility and mechanical stability of the cell. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and hereditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and hereditary elliptocytosis. The disease severity is primarily dependent on the extent of membrane surface area loss. Both these diseases can be readily diagnosed by various laboratory approaches that include red blood cell cytology, flow cytometry, ektacytometry, electrophoresis of the red cell membrane proteins, and mutational analysis of gene encoding red cell membrane proteins.

  12. Deep coverage mouse red blood cell proteome: a first comparison with the human red blood cell

    DEFF Research Database (Denmark)

    Pasini, Erica M; Kirkegaard, Morten; Salerno, Doris

    2008-01-01

    Mice have close genetic/physiological relationships to humans, breed rapidly, and can be genetically modified, making them the most used mammal in biomedical research. Because the red blood cell (RBC) is the sole gas transporter in vertebrates, diseases of the RBC are frequently severe; much...

  13. Rare hereditary red blood cell enzymopathies associated with hemolytic anemia - pathophysiology, clinical aspects, and laboratory diagnosis.

    Science.gov (United States)

    Koralkova, P; van Solinge, W W; van Wijk, R

    2014-06-01

    Hereditary red blood cell enzymopathies are genetic disorders affecting genes encoding red blood cell enzymes. They cause a specific type of anemia designated hereditary nonspherocytic hemolytic anemia (HNSHA). Enzymopathies affect cellular metabolism, which, in the red cell, mainly consists of anaerobic glycolysis, the hexose monophosphate shunt, glutathione metabolism, and nucleotide metabolism. Enzymopathies are commonly associated with normocytic normochromic hemolytic anemia. In contrast to other hereditary red cell disorders such as membrane disorders or hemoglobinopathies, the morphology of the red blood cell shows no specific abnormalities. Diagnosis is based on detection of reduced specific enzyme activity and molecular characterization of the defect on the DNA level. The most common enzyme disorders are deficiencies of glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). However, there are a number of other enzyme disorders, often much less known, causing HNSHA. These disorders are rare and often underdiagnosed, and the purpose of this review. In this brief review, we provide an overview of clinically relevant enzymes, their function in red cell metabolism, and key aspects of laboratory diagnosis.

  14. Mechanosensing Dynamics of Red blood Cells

    Science.gov (United States)

    Wan, Jiandi

    2015-11-01

    Mechanical stress-induced deformation of human red blood cells (RBCs) plays important physiopathological roles in oxygen delivery, blood rheology, transfusion, and malaria. Recent studies demonstrate that, in response to mechanical deformation, RBCs release adenosine-5'-triphosphate (ATP), suggesting the existence of mechanotransductive pathways in RBCs. Most importantly, the released ATP from RBCs regulates vascular tone and impaired release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. To date, however, the mechanisms of mechanotransductive release of ATP from RBCs remain unclear. Given that RBCs experience shear stresses continuously during the circulation cycle and the released ATP plays a central role in vascular physiopathology, understanding the mechanotransductive release of ATP from RBCs will provide not only fundamental insights to the role of RBCs in vascular homeostasis but also novel therapeutic strategies for red cell dysfunction and vascular disease. This talk describes the main research in my group on integrating microfluidic-based approaches to study the mechanosensing dynamics of RBCs. Specifically, I will introduce a micro?uidic approach that can probe the dynamics of shear-induced ATP release from RBCs with millisecond resolution and provide quantitative understandings of the mechanosensitive ATP release processes in RBCs. Furthermore, I will also describe our recent findings about the roles of the Piezo1 channel, a newly discovered mechanosensitive cation channel in the mechanotransductive ATP release in RBCs. Last, possible functions of RBCs in the regulation of cerebral blood flow will be discussed.

  15. Membrane-to-membrane transfer of tocopherol in red blood cells.

    Science.gov (United States)

    Tanaka, H; Mino, M

    1986-10-01

    The direct cell-to-cell transfer of tocopherol between red blood cells (RBCs) was examined. Two kinds of RBCs were provided; 1) Tocopherol-deficient ones showing complete dialuric acid-hemolysis and 2) tocopherol-supplemented ones showing no dialuric acid-hemolysis. The two kinds of RBCs were mixed and incubated with gentle swirling in a buffer solution. If no tocopherol transfer occurred between the two kinds of RBCs in the cell suspensions, hemolysis should not change during incubation because hemolysis is limited only in the -deficient cells in the suspensions. However, it was actually observed that when RBCs with adequate amounts of tocopherol were incubated with tocopherol-deficient RBCs, dialuric acid-induced hemolysis decreased during a 3-h incubation period. Contrarily, when an inadequate amount of tocopherol constituting a limiting level for inhibition of hemolysis, existed in RBCs which were mixed with -deficient ones, hemolysis increased after incubation. This indicates that tocopherol is transferred from the tocopherol-rich RBCs to the -deficient RBCs. The transfer was greater as the hematocrit of cell suspensions increased. Gum arabic contained in the suspensions inhibited the transfer, while bromelain (a protease which lowers the electric charge on the cell surface) increased it. These findings indicate that the transfer of tocopherol is related to the frequency of collision between cells.

  16. Red blood cell clusters in Poiseuille flow

    Science.gov (United States)

    Ghigliotti, Giovanni; Selmi, Hassib; Misbah, Chaouqi; Elasmi, Lassaad

    2011-11-01

    We present 2D numerical simulations of sets of vesicles (closed bags of a lipid bilayer membrane) in a parabolic flow, a setup that mimics red blood cells (RBCs) in the microvasculature. Vesicles, submitted to sole hydrodynamical interactions, are found to form aggregates (clusters) of finite size. The existence of a maximal cluster size is pointed out and characterized as a function of the flow intensity and the swelling ratio of the vesicles. Moreover bigger clusters move at lower velocity, a fact that may prove of physiological interest. These results quantify previous observations of the inhomogeneous distribution of RBCs in vivo (Gaehtgens et al., Blood Cells 6 - 1980). An interpretation of the phenomenon is put forward based on the presence of boli (vortices) between vesicles. Both the results and the explanation can be transposed to the three-dimensional case.

  17. The negative regulation of red cell mass by neocytolysis: physiologic and pathophysiologic manifestations.

    Science.gov (United States)

    Rice, Lawrence; Alfrey, Clarence P

    2005-01-01

    We have uncovered a physiologic process which negatively regulates the red cell mass by selectively hemolyzing young circulating red blood cells. This allows fine control of the number of circulating red blood cells under steady-state conditions and relatively rapid adaptation to new environments. Neocytolysis is initiated by a fall in erythropoietin levels, so this hormone remains the major regulator of red cell mass both with anemia and with red cell excess. Physiologic situations in which there is increased neocytolysis include the emergence of newborns from the hypoxic uterine environment and the descent of polycythemic high-altitude dwellers to sea level. The process first became apparent while investigating the mechanism of the anemia that invariably occurs after spaceflight. Astronauts experience acute central plethora on entering microgravity resulting in erythropoietin suppression and neocytolysis, but the reduced blood volume and red cell mass become suddenly maladaptive on re-entry to earth's gravity. The pathologic erythropoietin deficiency of renal disease precipitates neocytolysis, which explains the prolongation of red cell survival consistently resulting from erythropoietin therapy and points to optimally efficient erythropoietin dosing schedules. Implications should extend to a number of other physiologic and pathologic situations including polycythemias, hemolytic anemias, 'blood-doping' by elite athletes, and oxygen therapy. It is likely that erythropoietin influences endothelial cells which in turn signal reticuloendothelial phagocytes to destroy or permit the survival of young red cells marked by surface molecules. Ongoing studies to identify the molecular targets and cytokine intermediaries should facilitate detection, dissection and eventual therapeutic manipulation of the process. Copyright (c) 2005 S. Karger AG, Basel.

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... a waste product) from your body. Anemia also can occur if your red blood cells don't ... have less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, ...

  19. Reflectance confocal microscopy of red blood cells: simulation and experiment (Conference Presentation)

    Science.gov (United States)

    Zeidan, Adel; Yeheskely-Hayon, Daniella; Minai, Limor; Yelin, Dvir

    2016-03-01

    The properties of red blood cells are a remarkable indicator of the body's physiological condition; their density could indicate anemia or polycythemia, their absorption spectrum correlates with blood oxygenation, and their morphology is highly sensitive to various pathologic states including iron deficiency, ovalocytosis, and sickle cell disease. Therefore, measuring the morphology of red blood cells is important for clinical diagnosis, providing valuable indications on a patient's health. In this work, we simulated the appearance of normal red blood cells under a reflectance confocal microscope and discovered unique relations between the cells' morphological parameters and the resulting characteristic interference patterns. The simulation results showed good agreement with in vitro reflectance confocal images of red blood cells, acquired using spectrally encoded flow cytometry (SEFC) that imaged the cells during linear flow and without artificial staining. By matching the simulated patterns to the SEFC images of the cells, the cells' three-dimensional shapes were evaluated and their volumes were calculated. Potential applications include measurement of the mean corpuscular volume, cell morphological abnormalities, cell stiffness under mechanical stimuli, and the detection of various hematological diseases.

  20. Replication fork stability confers chemoresistance in BRCA-deficient cells

    DEFF Research Database (Denmark)

    Chaudhuri, Arnab Ray; Callen, Elsa; Ding, Xia;

    2016-01-01

    Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3....../4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11...... nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations...

  1. Treatment of pure red-cell aplasia with cyclosporine in a renal transplant patient.

    Science.gov (United States)

    Yildirim, Rahsan; Bilen, Yusuf; Keles, Mustafa; Uyanik, Abdullah; Gokbulut, Puren; Aydinli, Bulent

    2013-02-01

    Acquired pure red-cell aplasia is a rare disorder that can be either idiopathic or associated with certain autoimmune diseases, pregnancy, lymphoproliferative disorders, nutritional deficiencies, or medicines. We present a deceased-donor renal transplant patient who developed pure red-cell aplasia associated with mycophenolate mofetil or tacrolimus and was treated with cyclosporine. A 20-year-old woman was transplanted from a deceased donor 1 month earlier and presented to us with symptoms of fatigue, prostration, and palpitation. The results of a laboratory examination revealed anemia. A diagnostic work-up resulted in a diagnosis of pure red-cell aplasia. Mycophenolate mofetil was discontinued. Tacrolimus also was replaced with cyclosporine 2 months after mycophenolate mofetil was halted because of a lack of improvement in anemia. Three months later, her anemia improved with cyclosporine. Starting cyclosporine instead of tacrolimus or mycophenolate mofetil showed good improvement in our patient within 6 months of therapy.

  2. Red blood cell transfusion in septic shock

    DEFF Research Database (Denmark)

    Rosland, Ragnhild G; Hagen, Marte U; Haase, Nicolai

    2014-01-01

    BACKGROUND: Treating anaemia with red blood cell (RBC) transfusion is frequent, but controversial, in patients with septic shock. Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients. METHODS: We did a prospective cohort study at 7...... general intensive care units (ICUs) including all adult patients with septic shock in a 5-month period. RESULTS: Ninety-five of the 213 included patients (45%) received median 3 (interquartile range 2-5) RBC units during shock. The median pre-transfusion haemoglobin level was 8.1 (7.4-8.9) g....../dl and independent of shock day and bleeding. Patients with cardiovascular disease were transfused at higher haemoglobin levels. Transfused patients had higher Simplified Acute Physiology Score (SAPS) II (56 (45-69) vs. 48 (37-61), p = 0.0005), more bleeding episodes, lower haemoglobin levels days 1 to 5, higher...

  3. Value of red blood cell parameters in identifying pregnancy with thalassemia and pregnancy with iron-deficiency anemia%红细胞指标对妊娠合并地中海贫血和缺铁性贫血的鉴别价值

    Institute of Scientific and Technical Information of China (English)

    郭秋琼; 高飞雁

    2014-01-01

    目的:探讨红细胞指标对鉴别妊娠合并地中海贫血和缺铁性贫血的价值。方法选择妊娠合并地中海贫血者45例纳入地贫组,45例合并缺铁性贫血(IDA)的孕妇纳入IDA组,未合并地中海贫血和IDA的孕妇45例纳入对照组,比较三组孕妇红细胞指标参数。结果 RBC计数在IDA组明显低于地贫组及对照组,差异有统计学意义(P0.05);平均红细胞体积(MCV)在地贫组及IDA组均显著低于对照组(P0.05);红细胞体积分布宽度(RDW)在IDA组明显高于地贫组及对照组,且地贫组明显高于对照组,差异均有统计学意义(P<0.05)。结论红细胞指标中低MCV及高RDW是IDA的特征性改变,在妊娠期妇女合并地中海贫血与缺铁性贫血的鉴别诊断上具有实用价值。%Objective To investigate the value of red blood cell parameters in identifying pregnancy with thalassemia and pregnancy with iron-deficiency anemia. Methods 45 cases of pregnancy with thalassemia were in-cluded as thalassemia group, 45 cases of pregnancy with iron-deficiency anemia were included as IDA group and 45 cases of normal pregnancy were included as control group. The red cell parameters in each group were compared. Results RBC count in IDA group was significantly lower than that in thalassemia and control groups. There was no significant difference in RBC count between thalassemia and control group. MCV in thalassemia and IDA groups were significantly lower than that in control group. However, MCV in thalassemia and IDA groups showed no signifi-cant difference. RDW in IDA group was significantly higher than that of thalassemia and control group and RDW in thalassemia group was significantly higher than that in control group. Conclusion Low MCV and high RDW in red cell parameters were characteristic changes of IDA in pregnant women, which had practical values in the differential diagnosis of pregnancy with IDA and pregnancy with thalassemia.

  4. Augmented cell death with Bloom syndrome helicase deficiency.

    Science.gov (United States)

    Kaneko, Hideo; Fukao, Toshiyuki; Kasahara, Kimiko; Yamada, Taketo; Kondo, Naomi

    2011-01-01

    Bloom syndrome (BS) is a rare autosomal genetic disorder characterized by lupus-like erythematous telangi-ectasias of the face, sun sensitivity, infertility, stunted growth, upper respiratory infection, and gastrointestinal infections commonly associated with decreased immuno-globulin levels. The syndrome is associated with immuno-deficiency of a generalized type, ranging from mild and essentially asympto-matic to severe. Chromosomal abnormalities are hallmarks of the disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are diagnostic features. BS is caused by mutations in BLM, a member of the RecQ helicase family. We determined whether BLM deficiency has any effects on cell growth and death in BLM-deficient cells and mice. BLM-deficient EB-virus-transformed cell lines from BS patients and embryonic fibroblasts from BLM-/- mice showed slower growth than wild-type cells. BLM-deficient cells showed abnormal p53 protein expression after irradiation. In BLM-/- mice, small body size, reduced number of fetal liver cells and increased cell death were observed. BLM deficiency causes the up-regulation of p53, double-strand break and apoptosis, which are likely observed in irradiated control cells. Slow cell growth and increased cell death may be one of the causes of the small body size associated with BS patients.

  5. Growth and replication of red rain cells at 121°C and their red fluorescence

    Science.gov (United States)

    Gangappa, Rajkumar; Wickramasinghe, Chandra; Wainwright, Milton; Kumar, A. Santhosh; Louis, Godfrey

    2010-09-01

    We have shown that the red cells found in the Red Rain (which fell on Kerala, India, in 2001) survive and grow after incubation for periods of up to two hours at 121°C . Under these conditions daughter cells appear within the original mother cells and the number of cells in the samples increases with length of exposure to 121°C. No such increase in cells occurs at room temperature, suggesting that the increase in daughter cells is brought about by exposure of the Red Rain cells to high temperatures. This is an independent confirmation of results reported earlier by two of the present authors, claiming that the cells can replicate under high pressure at temperatures upto 300°C. The flourescence behaviour of the red cells is shown to be in remarkable correspondence with the extended red emission observed in the Red Rectagle planetary nebula and other galactic and extragalactic dust clouds, suggesting, though not proving an extraterrestrial origin.

  6. Growth and replication of red rain cells at 121 oC and their red fluorescence

    CERN Document Server

    Gangappa, Rajkumar; Wainwright, Milton; Kumar, A Santhosh; Louis, Godfrey

    2010-01-01

    We have shown that the red cells found in the Red Rain (which fell on Kerala, India, in 2001) survive and grow after incubation for periods of up to two hours at 121 oC . Under these conditions daughter cells appear within the original mother cells and the number of cells in the samples increases with length of exposure to 121 oC. No such increase in cells occurs at room temperature, suggesting that the increase in daughter cells is brought about by exposure of the Red Rain cells to high temperatures. This is an independent confirmation of results reported earlier by two of the present authors, claiming that the cells can replicate under high pressure at temperatures up to 300 oC. The flourescence behaviour of the red cells is shown to be in remarkable correspondence with the extended red emission observed in the Red Rectangle planetary nebula and other galactic and extragalactic dust clouds, suggesting, though not proving, an extraterrestrial origin.

  7. The evolution of pretransfusion testing: from agglutination to solid-phase red cell adherence tests.

    Science.gov (United States)

    Plapp, F V; Sinor, L T; Rachel, J M

    1989-01-01

    Hospital transfusion services and blood centers still use manual hemagglutination tests for most of their serological procedures. Automation of hemagglutination reactions has proven to be difficult, primarily because hemagglutination lacks an objective endpoint which can be easily interpreted by inexpensive instruments. Alternatively, solid-phase red cell adherence assays for ABO cell and serum grouping, Rh typing, red cell and platelet antibody screening, red cell and platelet crossmatching, IgA deficiency screening, hepatitis B surface antigen, and HIV antibody screening have been developed. The performance of these assays compares favorably with current hemagglutination and enzyme immunoassay methods. All of these tests share a common objective endpoint of adherence or nonadherence of indicator red cells. This uniformity allows easy interpretation of results visually, spectrophotometrically, or by image analysis. The latter technique has the potential to revolutionize the reading and interpretation of all agglutination tests. Solid-phase red cell adherence tests in microplates are ideal for batch processing large numbers of specimens. However, adherence tests are not restricted to this format. Therefore, blood grouping dipsticks have been produced, which permit testing of individual blood samples even outside of the laboratory.

  8. The homeostasis of Plasmodium falciparum-infected red blood cells.

    Directory of Open Access Journals (Sweden)

    Jakob M A Mauritz

    2009-04-01

    Full Text Available The asexual reproduction cycle of Plasmodium falciparum, the parasite responsible for severe malaria, occurs within red blood cells. A merozoite invades a red cell in the circulation, develops and multiplies, and after about 48 hours ruptures the host cell, releasing 15-32 merozoites ready to invade new red blood cells. During this cycle, the parasite increases the host cell permeability so much that when similar permeabilization was simulated on uninfected red cells, lysis occurred before approximately 48 h. So how could infected cells, with a growing parasite inside, prevent lysis before the parasite has completed its developmental cycle? A mathematical model of the homeostasis of infected red cells suggested that it is the wasteful consumption of host cell hemoglobin that prevents early lysis by the progressive reduction in the colloid-osmotic pressure within the host (the colloid-osmotic hypothesis. However, two critical model predictions, that infected cells would swell to near prelytic sphericity and that the hemoglobin concentration would become progressively reduced, remained controversial. In this paper, we are able for the first time to correlate model predictions with recent experimental data in the literature and explore the fine details of the homeostasis of infected red blood cells during five model-defined periods of parasite development. The conclusions suggest that infected red cells do reach proximity to lytic rupture regardless of their actual volume, thus requiring a progressive reduction in their hemoglobin concentration to prevent premature lysis.

  9. Genetics Home Reference: transcobalamin deficiency

    Science.gov (United States)

    ... deficiency often develop a blood disorder called megaloblastic anemia . Megaloblastic anemia results in a shortage of red blood cells, ... and Prevention: Intellectual Disability (PDF) Children's Hospital Boston: Megaloblastic Pernicious Anemia Children's Hospital Boston: White Blood Cell Disorders CLIMB: ...

  10. Selenoprotein O deficiencies suppress chondrogenic differentiation of ATDC5 cells.

    Science.gov (United States)

    Yan, Jidong; Fei, Yao; Han, Yan; Lu, Shemin

    2016-10-01

    Selenoprotein O (Sel O) is a selenium-containing protein, but its function is still unclear. In the present study, we observed that the mRNA and protein expression levels of Sel O increased during chondrogenic induction of ATDC5 cells. The effects of Sel O on chondrocyte differentiation were then examined through shRNA-mediated gene silencing technique. The expression of Sel O was significantly suppressed at both mRNA and protein levels in a stable cell line transfected with a Sel O-specific target shRNA construct. Thereafter, we demonstrated that Sel O deficiencies suppress chondrogenic differentiation of ATDC5 cells. Sel O deficiencies inhibited expression of chondrogenic gene Sox9, Col II, and aggrecan. Sel O-deficient cells also accumulated a few cartilage glycosaminoglycans (GAGs) and decreased the activity of alkaline phosphatase (ALP). In addition, Sel O deficiencies inhibited chondrocyte proliferation through delayed cell cycle progression by suppression of cyclin D1 expression. Moreover, Sel O deficiencies induced chondrocyte death through cell apoptosis. In summary, we describe the expression patterns and the essential roles of Sel O in chondrocyte viability, proliferation, and chondrogenic differentiation. Additionally, Sel O deficiency-mediated impaired chondrogenesis may illustrate the mechanisms of Se deficiency in the pathophysiological process of the endemic osteoarthropathy.

  11. Red cell alloimmunisation in patients with different types of infections

    NARCIS (Netherlands)

    Evers, Dorothea; van der Bom, Johanna G; Tijmensen, Janneke; Middelburg, Rutger A; de Haas, Masja; Zalpuri, Saurabh; de Vooght, Karen M K; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C V; Hudig, Francisca; Zwaginga, Jaap Jan

    2016-01-01

    Red cell alloantigen exposure can cause alloantibody-associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case-control study within a sou

  12. Red cell alloimmunisation in patients with different types of infections.

    NARCIS (Netherlands)

    Evers, D.; Bom, J.G. Van Der; Tijmensen, J.; Middelburg, R.A.; Haas, M. de; Zalpuri, S.; Vooght, K.M. De; Kerkhof, D. van de; Visser, O; Pequeriaux, N.C.V.; Hudig, F.; Zwaginga, J.J.

    2016-01-01

    Red cell alloantigen exposure can cause alloantibody-associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case-control study within a sou

  13. Control of red blood cell mass during spaceflight

    Science.gov (United States)

    Lane, H. W.; Alfrey, C. P.; Driscoll, T. B.; Smith, S. M.; Nyquist, L. E.

    1996-01-01

    Data are reviewed from twenty-two astronauts from seven space missions in a study of red blood cell mass. The data show that decreased red cell mass in all astronauts exposed to space for more than nine days, although the actual dynamics of mass changes varies with flight duration. Possible mechanisms for these changes, including alterations in erythropoietin levels, are discussed.

  14. Red blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells

    Directory of Open Access Journals (Sweden)

    Heimo eMairbäurl

    2013-11-01

    Full Text Available During exercise the cardiovascular system has to warrant substrate supply to working muscle. The main function of red blood cells in exercise is the transport of O2 from the lungs to the tissues and the delivery of metabolically produced CO2 to the lungs for expiration. Hemoglobin also contributes to the blood’s buffering capacity, and ATP and NO release from red blood cells contributes to vasodilation and improved blood flow to working muscle. These functions require adequate amounts of red blood cells in circulation. Trained athletes, particularly in endurance sports, have a decreased hematocrit, which is sometimes called sports anemia. This is not anemia in a clinical sense because athletes have in fact an increased total mass of red blood cells and hemoglobin in circulation relative to sedentary individuals. The slight decrease in hematocrit by training is brought about by an increased plasma volume. The mechanisms that increase total red blood cell mass by training are not understood fully. Despite stimulated erythropoiesis, exercise can decrease the red blood cell mass by intravascular hemolysis mainly of senescent red blood cells, which is caused by mechanical rupture when red blood cells pass through capillaries in contracting muscles, and by compression of red cells e.g. in foot soles during running or in hand palms in weightlifters. Together, these adjustments cause a decrease in the average age of the population of circulating red blood cells in trained athletes. These younger red cells are characterized by improved oxygen release and deformability, both of which also improve tissue oxygen supply during exercise.

  15. Red blood cell vesiculation in hereditary hemolytic anemia

    Science.gov (United States)

    Alaarg, Amr; Schiffelers, Raymond M.; van Solinge, Wouter W.; van Wijk, Richard

    2013-01-01

    Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias. PMID

  16. Red blood cell vesiculation in hereditary hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Amr eAlaarg

    2013-12-01

    Full Text Available Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterised by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely asessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary

  17. Red blood cell vesiculation in hereditary hemolytic anemia.

    Science.gov (United States)

    Alaarg, Amr; Schiffelers, Raymond M; van Solinge, Wouter W; van Wijk, Richard

    2013-12-13

    Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias.

  18. Red blood cells in retinal vascular disorders.

    Science.gov (United States)

    Agrawal, Rupesh; Sherwood, Joseph; Chhablani, Jay; Ricchariya, Ashutosh; Kim, Sangho; Jones, Philip H; Balabani, Stavroula; Shima, David

    2016-01-01

    Microvascular circulation plays a vital role in regulating physiological functions, such as vascular resistance, and maintaining organ health. Pathologies such as hypertension, diabetes, or hematologic diseases affect the microcirculation posing a significant risk to human health. The retinal vasculature provides a unique window for non-invasive visualisation of the human circulation in vivo and retinal vascular image analysis has been established to predict the development of both clinical and subclinical cardiovascular, metabolic, renal and retinal disease in epidemiologic studies. Blood viscosity which was otherwise thought to play a negligible role in determining blood flow based on Poiseuille's law up to the 1970s has now been shown to play an equally if not a more important role in controlling microcirculation and quantifying blood flow. Understanding the hemodynamics/rheology of the microcirculation and its changes in diseased states remains a challenging task; this is due to the particulate nature of blood, the mechanical properties of the cells (such as deformability and aggregability) and the complex architecture of the microvasculature. In our review, we have tried to postulate a possible role of red blood cell (RBC) biomechanical properties and laid down future framework for research related to hemorrheological aspects of blood in patients with retinal vascular disorders.

  19. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

    Energy Technology Data Exchange (ETDEWEB)

    Canuto, K.S.; Guimaraes, O.R.; Geller, M. [Centro Universitario Serra dos Orgaos, Teresopolis, RJ (Brazil). Centro de Ciencias da Saude; Sergio, L.P.S. [Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro, RJ (Brazil). Departamento de Biofisica e Biometria; Paoli, F. [Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, MG (Brazil). Departamento de Morfologia; Fonseca, A.S., E-mail: adnfonseca@ig.com.br [Universidade Federal do Estado do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Departamento de Ciencias Fisiologicas

    2015-10-15

    Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia coli cells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficient E. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out. (author)

  20. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

    Directory of Open Access Journals (Sweden)

    K.S. Canuto

    2015-01-01

    Full Text Available Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia coli cells that were exposed to ultraviolet C (UVC radiation. Exponential and stationary wild-type and uvrA-deficient E. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC. Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

  1. Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  2. Dietary folic acid protects against genotoxicity in the red blood cells of mice

    Science.gov (United States)

    MacFarlane, Amanda J.; Behan, Nathalie A.; Field, Martha S.; Williams, Andrew; Stover, Patrick J.; Yauk, Carole L.

    2016-01-01

    Folate is an essential B vitamin required for the de novo synthesis of purines, thymidylate and methionine. Folate deficiency can lead to mutations and genome instability, and has been shown to exacerbate the genotoxic potential of environmental toxins. We hypothesized that a folic acid (FA) deficient diet would induce genotoxicity in mice as measured by the Pig-a mutant phenotype (CD24−) and micronuclei (MN) in reticulocytes (RET) and red blood cells/normochromatic erythrocytes (RBC/NCE). Male Balb/c mice were fed a FA deficient (0 mg/kg), control (2 mg/kg) or supplemented (6 mg/kg) diet from weaning for 18 wk. Mice fed the deficient diet had 70% lower liver folate (p control diet. RETCD24− and RBCCD24− frequencies were not different between mice fed the deficient and control diets. Compared to mice fed the FA supplemented diet, mice fed the deficient diet had 73% lower liver folate (p cells of mice. PMID:26177356

  3. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells.

    Science.gov (United States)

    Canuto, K S; Sergio, L P S; Guimarães, O R; Geller, M; Paoli, F; Fonseca, A S

    2015-10-01

    Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

  4. Abnormal red cell structure and function in neuroacanthocytosis.

    Directory of Open Access Journals (Sweden)

    Judith C A Cluitmans

    Full Text Available Panthothenate kinase-associated neurodegeneration (PKAN belongs to a group of hereditary neurodegenerative disorders known as neuroacanthocytosis (NA. This genetically heterogeneous group of diseases is characterized by degeneration of neurons in the basal ganglia and by the presence of deformed red blood cells with thorny protrusions, acanthocytes, in the circulation.The goal of our study is to elucidate the molecular mechanisms underlying this aberrant red cell morphology and the corresponding functional consequences. This could shed light on the etiology of the neurodegeneration.We performed a qualitative and semi-quantitative morphological, immunofluorescent, biochemical and functional analysis of the red cells of several patients with PKAN and, for the first time, of the red cells of their family members.We show that the blood of patients with PKAN contains not only variable numbers of acanthocytes, but also a wide range of other misshapen red cells. Immunofluorescent and immunoblot analyses suggest an altered membrane organization, rather than quantitative changes in protein expression. Strikingly, these changes are not limited to the red blood cells of PKAN patients, but are also present in the red cells of heterozygous carriers without neurological problems. Furthermore, changes are not only present in acanthocytes, but also in other red cells, including discocytes. The patients' cells, however, are more fragile, as observed in a spleen-mimicking device.These morphological, molecular and functional characteristics of red cells in patients with PKAN and their family members offer new tools for diagnosis and present a window into the pathophysiology of neuroacanthocytosis.

  5. Iron deficiency anemia

    Science.gov (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  6. Electrochemical Red Blood Cell Counting: One at a Time.

    Science.gov (United States)

    Sepunaru, Lior; Sokolov, Stanislav V; Holter, Jennifer; Young, Neil P; Compton, Richard G

    2016-08-08

    We demonstrate that the concentration of a red blood cell solution under physiological conditions can be determined by electrochemical voltammetry. The magnitude of the oxygen reduction currents produced at an edge-plane pyrolytic graphite electrode was diagnosed analytically at concentrations suitable for a point-of-care test device. The currents could be further enhanced when the solution of red blood cells was exposed to hydrogen peroxide. We show that the enhanced signal can be used to detect red blood cells at a single entity level. The method presented relies on the catalytic activity of red blood cells towards hydrogen peroxide and on surface-induced haemolysis. Each single cell activity is expressed as current spikes decaying within a few seconds back to the background current. The frequency of such current spikes is proportional to the concentration of cells in solution.

  7. Lack of Erythropoietic Inhibitory Effect of Serum From Patients with Congenital Pure Red Cell Aplasia

    Science.gov (United States)

    Geller, Gary; And Others

    1975-01-01

    Serum of five children ages 1 to 19 months with congenital pure red cell aplasia (incomplete or defective development of red blood cells) was injected in normal mice to determine possible inhibition of red blood cell formulating stimulants. (CL)

  8. [Promising technologies of packed red blood cells production and storage].

    Science.gov (United States)

    Maksimov, A G; Golota, A S; Krassiĭ, A B

    2013-10-01

    The current article is dedicated to promising technologies of packed red blood cells production and storage. The following new technical approaches are presented: (1) erythrocytes storage in strict anaerobic argon-hydrogen environment, (2) lyophilization of erythrocyte suspension by its atomization in nitrogen gas, (3) lyophilization of erythrocytes by directional freezing under the influence of radio frequency radiation, (4) automated pharming of antigen free packed red blood cells from progenitor cell directly at the battlefield.

  9. Red blood cell lifespan, erythropoiesis and hemoglobin control.

    Science.gov (United States)

    Kruse, Anja; Uehlinger, Dominik E; Gotch, Frank; Kotanko, Peter; Levin, Nathan W

    2008-01-01

    Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

  10. Red cell exchange: special focus on sickle cell disease.

    Science.gov (United States)

    Kim, Haewon C

    2014-12-05

    The primary function of red blood cells (RBCs) is to deliver oxygen from the lungs to tissues. Tissue hypoxia occurs when the oxygen-carrying capacity of RBCs is compromised due primarily to 3 causes: (1) a reduction in circulating RBC mass, (2) an increase in circulating RBC mass, or (3) abnormal hemoglobin (Hb) that either does not sufficiently release oxygen to tissues (high-oxygen-affinity hemoglobin) or occludes the microvasculature due to deformed RBCs (sickled RBCs). To improve oxygenation in patients with reduced or increased RBC mass, RBC administration (simple transfusion) or RBC removal (RBC depletion) is performed, respectively. However, for patients with abnormal Hb, RBCs containing abnormal Hb are removed and replaced by healthy volunteer donor RBCs by red cell exchange (RCE). RCE can be performed by manual exchange or by automated exchange using a blood cell separator (erythrocytapheresis). In this review, indications for RCE in sickle cell disease using the evidence-based American Society for Apheresis categories(1) are presented and the rationale for RCE in each disorder are discussed. Simple transfusion versus RCE and manual RCE versus automated RCE are compared. Finally, this review briefly presents some of the challenges of performing erythrocytapheresis in small children and discusses various choices for central venous access during RCE.(2.)

  11. Microfluidic Device for Continuous Magnetophoretic Separation of Red Blood Cells

    CERN Document Server

    Iliescu, Ciprian; Avram, Marioara; Xu, G; Avram, Andrei

    2008-01-01

    This paper presents a microfluidic device for magnetophoretic separation red blood cells from blood under contionous flow. The separation method consist of continous flow of a blood sample (diluted in PBS) through a microfluidic channel which presents on the bottom "dots" of feromagnetic layer. By appling a magnetic field perpendicular on the flowing direction, the feromagnetic "dots" generates a gradient of magnetic field which amplifies the magnetic force. As a result, the red blood cells are captured on the bottom of the microfluidic channel while the rest of the blood is collected at the outlet. Experimental results show that an average of 95 % of red blood cells are trapped in the device

  12. Dysferlin and other non-red cell proteins accumulate in the red cell membrane of Diamond-Blackfan Anemia patients.

    Directory of Open Access Journals (Sweden)

    Esther N Pesciotta

    Full Text Available Diamond Blackfan Anemia (DBA is a congenital anemia usually caused by diverse mutations in ribosomal proteins. Although the genetics of DBA are well characterized, the mechanisms that lead to macrocytic anemia remain unclear. We systematically analyzed the proteomes of red blood cell membranes from multiple DBA patients to determine whether abnormalities in protein translation or erythropoiesis contribute to the observed macrocytosis or alterations in the mature red blood cell membrane. In depth proteome analysis of red cell membranes enabled highly reproducible identification and quantitative comparisons of 1100 or more proteins. These comparisons revealed clear differences between red cell membrane proteomes in DBA patients and healthy controls that were consistent across DBA patients with different ribosomal gene mutations. Proteins exhibiting changes in abundance included those known to be increased in DBA such as fetal hemoglobin and a number of proteins not normally found in mature red cell membranes, including proteins involved in the major histocompatibility complex class I pathway. Most striking was the presence of dysferlin in the red blood cell membranes of DBA patients but absent in healthy controls. Immunoblot validation using red cell membranes isolated from additional DBA patients and healthy controls confirmed a distinct membrane protein signature specific to patients with DBA.

  13. Copper deficiency and effects of copper supplementation in a herd of red deer (Cervus elaphus

    Directory of Open Access Journals (Sweden)

    Bernhoft Aksel

    2008-04-01

    Full Text Available Abstract Copper (Cu deficiency was diagnosed in a Norwegian red deer (Cervus elaphus herd subsequent to deaths due to emaciation in late autumn 1999. The animals had free access to salt licks containing 3000 mg Cu/kg. An evaluation of the herd revealed poor calf growth rate, low weights of adult hinds, dull and light-coloured hair coats and cases of diarrhoea. The herd was subsequently monitored throughout a three-year period of Cu-supplementation. The monitoring regimen included clinical observation, copper serum examination, weighing, faecal parasitological examination, and reproduction control by ultrasound. During the period January 2000 to May 2001, the animals were treated with Cu oxid capsules (1 g CuO/10 kg liveweight at 2–4 months intervals, with the exception of March to September 2000. The animals were fed continuously with Cu-enriched concentrates containing 300 mg Cu/kg, at a rate of 1/2 kg per head and day, from May 2001 to January 2003. Following both copper supplementation regimens adequate serum Cu concentrations were measured, and markedly improved body weights, coat quality and reproductive results were observed, except for the period from March to September 2000 when no treatment was given. The results showed that in a deer herd, with a diet low in Cu, supplementation with CuO capsules had to be given at intervals of a few months to maintain adequate serum Cu levels. Free access to Cu-containing salt licks did not meet the animals' Cu demand. Good and stable results were achieved by the daily feeding of Cu-enriched concentrates.

  14. Red cell parameters in infant and children from the Arabian Peninsula

    OpenAIRE

    Mekaini, Lolowa A Al; Denic, Srdjan; Jabri, Omar N Al; Narchi, Hassib; Souid, Abdul-Kader; Al-Hammadi, Suleiman

    2015-01-01

    α+-Thalassemia trait and iron deficiency anemia are frequent causes of microcytosis and a common diagnostic challenge in Arabian children. In this study, their prevalences and effects on the red cell parameters were evaluated in 28,457 children aged one day to 6 years. α+-Thalassemia trait was considered to be present when mean cell volume (MCV) was 14.5%. The prevalence of α+-thalassemia trait was 15.7% (502/3,191), which was similar to previously reported values for adults (9-14%). Iron def...

  15. Automated red blood cell analysis compared with routine red blood cell morphology by smear review

    Directory of Open Access Journals (Sweden)

    Dr.Poonam Radadiya

    2015-01-01

    Full Text Available The RBC histogram is an integral part of automated haematology analysis and is now routinely available on all automated cell counters. This histogram and other associated complete blood count (CBC parameters have been found abnormal in various haematological conditions and may provide major clues in the diagnosis and management of significant red cell disorders. Performing manual blood smears is important to ensure the quality of blood count results and to make presumptive diagnosis. In this article we have taken 100 samples for comparative study between RBC histograms obtained by automated haematology analyzer with peripheral blood smear. This article discusses some morphological features of dimorphism and the ensuing characteristic changes in their RBC histograms.

  16. Neonatal management and outcome in red cell alloimmunization

    NARCIS (Netherlands)

    Smits-Wintjens, Vivianne Elise Huberta Johanna

    2012-01-01

    In this thesis, several studies on neonatal red cell alloimmune hemolytic disease are presented, including various management options, associated complications and co-morbidities and the short-term and long-term outcome of children with Rhesus hemolytic disease.

  17. Acquired pure red cell aplasia in a child.

    Directory of Open Access Journals (Sweden)

    Sharma R

    2002-01-01

    Full Text Available Primary acquired pure red cell aplasia is a rare occurrence in childhood. An eleven-year old boy presented to us with pallor, which required multiple packed red cell transfusions. He did not have hepatosplenomegaly, jaundice or lymphadenopathy. Bone marrow examination revealed the diagnosis of pure red cell aplasia. All possible investigations were done to exclude secondary causes of pure red cell aplasia. No secondary cause was found on investigations. Rheumatoid factor and anti-nuclear antibodies were positive. He was started on oral steroids, to which he did not respond. He was then given cyclosporine A. Response to cyclosporine was dramatic and the child now does not require any transfusions.

  18. Neonatal management and outcome in red cell alloimmunization

    NARCIS (Netherlands)

    Smits-Wintjens, Vivianne Elise Huberta Johanna

    2012-01-01

    In this thesis, several studies on neonatal red cell alloimmune hemolytic disease are presented, including various management options, associated complications and co-morbidities and the short-term and long-term outcome of children with Rhesus hemolytic disease.

  19. Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

    OpenAIRE

    Ioana Mozos

    2015-01-01

    The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular dise...

  20. Research progress on the red cell diseases in China

    Institute of Scientific and Technical Information of China (English)

    YUE Lan-zhu; SHAO Zong-hong

    2012-01-01

    In recent years,there have been lots of progresses in the studies on red cell diseases in China,especially bone marrow failure diseases including immune-related pancytopenia,aplastic anemia,myelodysplastic syndrome,and paroxymal nocturnal hemoglobinuria.Numerous laboratory experiments as well as clinical researches have been carried out by Chinese hematologists,which brought about much clearer pathogenesis,more rational diagnosis methods and more effective therapies for red cell diseases.

  1. Elastic thickness compressibilty of the red cell membrane.

    OpenAIRE

    Heinrich, V; Ritchie, K; Mohandas, N; Evans, E.

    2001-01-01

    We have used an ultrasensitive force probe and optical interferometry to examine the thickness compressibility of the red cell membrane in situ. Pushed into the centers of washed-white red cell ghosts lying on a coverglass, the height of the microsphere-probe tip relative to its closest approach on the adjacent glass surface revealed the apparent material thickness, which began at approximately 90 nm per membrane upon detection of contact (force approximately 1-2 pN). With further impingement...

  2. Chromosomal replication incompatibility in Dam methyltransferase deficient Escherichia coli cells

    DEFF Research Database (Denmark)

    Freiesleben, Ulrik Von

    1996-01-01

    Dam methyltransferase deficient Escherichia coli cells containing minichromosomes were constructed. Free plasmid DNA could not be detected in these cells and the minichromosomes were found to be integrated in multiple copies in the origin of replication (oriC) region of the host chromosome...

  3. Myosin IIA deficient cells migrate efficiently despite reduced traction forces at cell periphery

    Directory of Open Access Journals (Sweden)

    Melissa H. Jorrisch

    2013-02-01

    Cell motility is a cornerstone of embryogenesis, tissue remodeling and repair, and cancer cell invasion. It is generally thought that migrating cells grab and exert traction force onto the extracellular matrix in order to pull the cell body forward. While previous studies have shown that myosin II deficient cells migrate efficiently, whether these cells exert traction forces during cell migration in the absence of the major contractile machinery is currently unknown. Using an array of micron-sized pillars as a force sensor and shRNA specific to each myosin II isoform (A and B, we analyzed how myosin IIA and IIB individually regulate cell migration and traction force generation. Myosin IIA and IIB localized preferentially to the leading edge where traction force was greatest, and the trailing edge, respectively. When individual myosin II isoforms were depleted by shRNA, myosin IIA deficient cells lost actin stress fibers and focal adhesions, whereas myosin IIB deficient cells maintained similar actin organization and focal adhesions as wild-type cells. Interestingly, myosin IIA deficient cells migrated faster than wild-type or myosin IIB deficient cells on both a rigid surface and a pillar array, yet myosin IIA deficient cells exerted significantly less traction force at the leading edge than wild-type or myosin IIB deficient cells. These results suggest that, in the absence of myosin IIA mediated force-generating machinery, cells move with minimal traction forces at the cell periphery, thus demonstrating the remarkable ability of cells to adapt and migrate.

  4. Myosin IIA deficient cells migrate efficiently despite reduced traction forces at cell periphery.

    Science.gov (United States)

    Jorrisch, Melissa H; Shih, Wenting; Yamada, Soichiro

    2013-04-15

    Cell motility is a cornerstone of embryogenesis, tissue remodeling and repair, and cancer cell invasion. It is generally thought that migrating cells grab and exert traction force onto the extracellular matrix in order to pull the cell body forward. While previous studies have shown that myosin II deficient cells migrate efficiently, whether these cells exert traction forces during cell migration in the absence of the major contractile machinery is currently unknown. Using an array of micron-sized pillars as a force sensor and shRNA specific to each myosin II isoform (A and B), we analyzed how myosin IIA and IIB individually regulate cell migration and traction force generation. Myosin IIA and IIB localized preferentially to the leading edge where traction force was greatest, and the trailing edge, respectively. When individual myosin II isoforms were depleted by shRNA, myosin IIA deficient cells lost actin stress fibers and focal adhesions, whereas myosin IIB deficient cells maintained similar actin organization and focal adhesions as wild-type cells. Interestingly, myosin IIA deficient cells migrated faster than wild-type or myosin IIB deficient cells on both a rigid surface and a pillar array, yet myosin IIA deficient cells exerted significantly less traction force at the leading edge than wild-type or myosin IIB deficient cells. These results suggest that, in the absence of myosin IIA mediated force-generating machinery, cells move with minimal traction forces at the cell periphery, thus demonstrating the remarkable ability of cells to adapt and migrate.

  5. Generation of Peroxisome-Deficient Somatic Animal Cell Mutants.

    Science.gov (United States)

    Okumoto, Kanji; Fujiki, Yukio

    2017-01-01

    Cell mutants with a genetic defect affecting various cellular phenotypes are widely utilized as a powerful tool in genetic, biochemical, and cell biological research. More than a dozen complementation groups of animal somatic mutant cells defective in peroxisome biogenesis have been successfully isolated in Chinese hamster ovary (CHO) cells and used as a model system reflecting fatal human severe genetic disorders named peroxisome biogenesis disorders (PBD). Isolation and characterization of peroxisome-deficient CHO cell mutants has allowed the identification of PEX genes and the gene products peroxins, which directly leads to the accomplishment of isolation of pathogenic genes responsible for human PBDs, as well as elucidation of their functional roles in peroxisome biogenesis. Here, we describe the procedure to isolate peroxisome-deficient mammalian cell mutants from CHO cells, by making use of an effective, photo-sensitized selection method.

  6. Iron deficiency.

    Science.gov (United States)

    Scrimshaw, N S

    1991-10-01

    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world.

  7. A role for activated endothelial cells in red blood cell clearance: implications for vasopathology

    DEFF Research Database (Denmark)

    Fens, Marcel H A M; van Wijk, Richard; Andringa, Grietje

    2012-01-01

    Background Phosphatidylserine exposure by red blood cells is acknowledged as a signal that initiates phagocytic removal of the cells from the circulation. Several disorders and conditions are known to induce phosphatidylserine exposure. Removal of phosphatidylserine-exposing red blood cells gener...... cells play a role in red blood cell clearance in vivo. Significant erythrophagocytosis can induce endothelial cell loss, which may contribute to vasopathological effects as seen, for instance, in sickle cell disease.......Background Phosphatidylserine exposure by red blood cells is acknowledged as a signal that initiates phagocytic removal of the cells from the circulation. Several disorders and conditions are known to induce phosphatidylserine exposure. Removal of phosphatidylserine-exposing red blood cells...... generally occurs by macrophages in the spleen and liver. Previously, however, we have shown that endothelial cells are also capable of erythrophagocytosis. Key players in the erythrophagocytosis by endothelial cells appeared to be lactadherin and αv-integrin. Phagocytosis via the phosphatidylserine...

  8. Quantification of depletion-induced adhesion of Red Blood Cells

    CERN Document Server

    Steffen, Patrick; Wagner, Christian

    2012-01-01

    Red blood cells (RBC) are known to form aggregates in the forms of rouleaux due to the presence of plasma proteins under physiological conditions. Rouleaux formation can be also induced in vitro by the addition of macromolecules to the RBC solution. Current data on the adhesion strength between red blood cells in their natural discocyte shapes mostly rely on indirect measurements like flow chamber experiments, but on the single cell level data is lacking. Here we present measurements on the dextran induced aggregation of red blood cells by use of atomic force microscopy based single cell force spectroscopy (SCFS). The effects of dextran concentration and molecular weight on the interaction energy of adhering RBCs was determined. The results are in good agreement with a model based on the depletion effect and former experimental studies.

  9. Radiolabeled red blood cells: status, problems, and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1983-01-01

    Radionuclidic labels for red cells can be divided into two main categories - cohort or pulse labels, and random labels. The random labels are incorporated into circulating cells of all ages and the labeling process is usually carried out in vitro. The red cell labels in predominant use involve random labeling and employ technetium-99m, chromium-51, indium-111, and gallium-68, roughly in that order. The extent of usefulness depends on the properties of the label such as the half-life, decay mode, and in-vivo stability, etc. Labeled cells can be used for red cell survival measurements when the half-life of the radionuclide is sufficiently long. The major portion of this article deals with random labels.

  10. Sirt1 deficiency attenuates spermatogenesis and germ cell function.

    Directory of Open Access Journals (Sweden)

    Matthew Coussens

    Full Text Available In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, and mitochondrial respiration. The initial investigations of Sirt1 deficient mice have revealed a phenotype that includes a reduced lifespan, small size, and an increased frequency of abnormal sperm. We have now performed a detailed analysis of the molecular and functional effects of Sirt1 deficiency in the germ line of Sirt1 knock-out (-/- mice. We find that Sirt1 deficiency markedly attenuates spermatogenesis, but not oogenesis. Numbers of mature sperm and spermatogenic precursors, as early as d15.5 of development, are significantly reduced ( approximately 2-10-fold less; Pdeficiency did not effect the efficiency oocyte production following superovulation of female mice. Furthermore, the proportion of mature sperm with elevated DNA damage ( approximately 7.5% of total epididymal sperm; P = 0.02 was significantly increased in adult Sirt1-/- males. Analysis of global gene expression by microarray analysis in Sirt1 deficient testis revealed dysregulated expression of 85 genes, which were enriched (P<0.05 for genes involved in spermatogenesis and protein sumoylation. To assess the function of Sirt1 deficient germ cells, we compared the efficiency of generating embryos and viable offspring in in vitro fertilization (IVF experiments using gametes from Sirt1-/- and sibling Sirt1+/- mice. While viable animals were derived in both Sirt1-/- X wild type and Sirt1-/- X Sirt1-/- crosses, the efficiency of producing both 2-cell zygotes and viable offspring was diminished when IVF was performed with Sirt1-/- sperm and/or oocytes. Together, these data support an important role for Sirt1 in spermatogenesis, including spermatogenic stem cells, as well as germ cell

  11. Deficient natural killer cell function in preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Alanen, A.; Lassila, O.

    1982-11-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.

  12. The effect of oxidative stress on human red cells glutathione peroxidase, glutathione reductase level, and prevalence of anemia among diabetics

    Directory of Open Access Journals (Sweden)

    Hisham Waggiallah

    2011-01-01

    Full Text Available Background: The oxidative stress is considered as major consequence of diabetes mellitus affecting red cell antioxidant enzymes. Aim: The present study was conducted to assess the impact of oxidative stress (reduced glutathione on glutathione peroxidase, and glutathione reductse and prevalence of anemia among diabetic patients. Materials and Methods: The study involved 100 adult patients attending Buraidah Central Hospital and 30 healthy controls. Blood samples were collected and analyzed for glutathione (GSH concentration, glutathione peroxidase (GPO, glutathione reductase (GR, fasting blood sugar (RBS, hemoglobin (HGB, red cell count (RBCs hematocrit (HCT mean cell volume (MCV mean cell hemoglobin (MCH and mean cell hemoglobin concentration (MCHC and hemoglobin A1c. Blood urea, serum creatinine, and microalbuminuria were measured to exclude diabetes mellitus nephropathy. Results : were obtained showed significant correlation between deficiency of glutathione peroxidase, glutathione reductase and deficient of glutathione among diabetics, which has significant correlation between low hemoglobin concentration (females <120 g/L, males <130 g/L, also there is low concentration of red cell count and red cell indices (MCV, MCH and MCHC. The prevalence of anemia was 22% in diabetes patients. Conclusion: It can be concluded that there is strong significant effect of oxidative stress (reduced glutathione on glutathione peroxidase, glutathione reductase level these may reduce hemoglobin concentration in diabetic patients. This means oxidative stress of diabetes mellitus is the possible cause of anemia in diabetics without nephropathy.

  13. Pure Red Cell Aplasia Following Interleukin-2 Therapy

    Directory of Open Access Journals (Sweden)

    Janice P. Dutcher MD

    2016-04-01

    Full Text Available A 61-year-old woman with metastatic renal cell carcinoma underwent systemic treatment with high-dose interleukin-2 (IL-2. Anemia requiring transfusion of 1 unit of packed red blood cells (PRBCs was required during the second week of IL-2 therapy. One month following completion of high-dose IL-2 treatment, she was hospitalized for severe, symptomatic anemia and received 5 units of PRBCs. She was referred back for evaluation. A complete hematologic evaluation was performed including antiviral serology, evaluation for hemolysis, complete iron studies, and finally bone marrow aspiration and biopsy. The diagnosis was pure red cell aplasia, and no inciting viral cause could be ascertained. She required PRBCs for 5 months following IL-2 therapy. It was concluded that IL-2 was the cause of her red cell aplasia. This subsequently resolved spontaneously, and she had normal hemoglobin and hematocrit, respectively, 1 and 2 years after treatment.

  14. Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.

  15. Mechanisms linking red blood cell disorders and cardiovascular diseases.

    Science.gov (United States)

    Mozos, Ioana

    2015-01-01

    The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.

  16. 琥珀酸亚铁片对妊娠合并缺铁性贫血的疗效及血红蛋白、红细胞、血清铁蛋白的影响%Efficacy of ferrous succinate tablets on iron deficiency anemia during pregnancy and impact on hemoglobin, red blood cells, serum ferritin

    Institute of Scientific and Technical Information of China (English)

    徐谟燕; 柴竟竟

    2014-01-01

    目的:观察琥珀酸亚铁片对妊娠合并缺铁性贫血( IDA)的治疗效果及其对血红蛋白( Hb)、红细胞( RBC)、血清铁蛋白( SF)的影响。方法选择我院2011年1月至2012年12月的妊娠合并缺铁性贫血患者120例(均符合入选标准),其中轻度贫血107例,中度贫血13例,重度贫血0例,给患者口服琥珀酸亚铁片,1~2片/次,3次/d。分别测定治疗前后孕妇的Hb、RBC和SF,观察并记录实验过程中出现的不良反应,评价药物的安全性。结果120例妊娠合并缺铁性贫血患者39例痊愈,57例显效,22例有效,2例无效,总有效率为98.3%。治疗后Hb、RBC和SF与治疗前比较差异有统计学意义(P<0.01)。治疗过程中部分患者出现轻微的不良反应,均未影响治疗效果。结论琥珀酸亚铁片对妊娠合并缺铁性贫血有显著的治疗效果,能明显提高妊娠合并缺铁性贫血患者的Hb、RBC和SF。%Objective To study the therapeutic effect of ferrous succinate tablets on iron deficiency anemia ( IDA) during pregnancy and impact on hemoglobin ( Hb) ,red blood cell ( RBC) ,serum ferritin ( SF) . Methods 120 IDA patients during pregnancy from January 2011 to December 2012 in our hospital were selected,there were 107 cases of mild anemia,13 cases of moderate anemia,no severe anemia. All patients were given oral ferrous succinate tablets 1~2 tables once,3 times a day. Hb,RBC and SF levels before and after treatment were measured. The adverse reactions during the experiment were observed and recorded,and the drug safety was evaluated. Results There were 39 cases cured,57 cases markedly effective,22 cases effective in the 120 cases of pregnant women with IDA after taking ferrous succinate tablets,only two cases invalid. The total effective rate was 98. 3%. HB,RBC,SF were significantly increased after treatment than before treatment (P<0. 01). In addition,patients during the treatment although had some mild side effects,but it did not affect the

  17. Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition

    Directory of Open Access Journals (Sweden)

    Kinoshita Ayako

    2005-05-01

    Full Text Available Abstract Background Cell simulation, which aims to predict the complex and dynamic behavior of living cells, is becoming a valuable tool. In silico models of human red blood cell (RBC metabolism have been developed by several laboratories. An RBC model using the E-Cell simulation system has been developed. This prototype model consists of three major metabolic pathways, namely, the glycolytic pathway, the pentose phosphate pathway and the nucleotide metabolic pathway. Like the previous model by Joshi and Palsson, it also models physical effects such as osmotic balance. This model was used here to reconstruct the pathology arising from hereditary glucose-6-phosphate dehydrogenase (G6PD deficiency, which is the most common deficiency in human RBC. Results Since the prototype model could not reproduce the state of G6PD deficiency, the model was modified to include a pathway for de novo glutathione synthesis and a glutathione disulfide (GSSG export system. The de novo glutathione (GSH synthesis pathway was found to compensate partially for the lowered GSH concentrations resulting from G6PD deficiency, with the result that GSSG could be maintained at a very low concentration due to the active export system. Conclusion The results of the simulation were consistent with the estimated situation of real G6PD-deficient cells. These results suggest that the de novo glutathione synthesis pathway and the GSSG export system play an important role in alleviating the consequences of G6PD deficiency.

  18. Cobalt uptake and binding in human red blood cells

    DEFF Research Database (Denmark)

    Simonsen, Lars Ole; Brown, Anthony M; Harbak, Henrik

    2011-01-01

    The basal uptake and cytoplasmic binding of cobalt was studied in human red cells using (57)Co as tracer. The basal uptake is linear with time, at a rate of about 10 µmol (l cells)(-1) h(-1) at 100 µM [Co(2+)](o), and is almost irreversible, as there is hardly any efflux into excess EDTA. Ionophore...

  19. Micronuclei in red blood cells of armored catfish Hypostomus ...

    African Journals Online (AJOL)

    SERVER

    2008-04-03

    Apr 3, 2008 ... 1Centro Universitário Metodista - Porto Alegre - RS –Brazil. 2Department of ... 2,000 red blood cells of animals subjected to treatment, it was possible to observe 8.25 ± 0.02% cells .... The social impact of this contamination of.

  20. Challenges for red blood cell biomarker discovery through proteomics

    NARCIS (Netherlands)

    Barasa, B.A.; Slijper, M.

    2014-01-01

    Red blood cells are rather unique body cells, since they have lost all organelles when mature, which results in lack of potential to replace proteins that have lost their function. They maintain only a few pathways for obtaining energy and reducing power for the key functions they need to fulfill. T

  1. Computational Biomechanics of Human Red Blood Cells in Hematological Disorders.

    Science.gov (United States)

    Li, Xuejin; Li, He; Chang, Hung-Yu; Lykotrafitis, George; Em Karniadakis, George

    2017-02-01

    We review recent advances in multiscale modeling of the biomechanical characteristics of red blood cells (RBCs) in hematological diseases, and their relevance to the structure and dynamics of defective RBCs. We highlight examples of successful simulations of blood disorders including malaria and other hereditary disorders, such as sickle-cell anemia, spherocytosis, and elliptocytosis.

  2. Challenges for red blood cell biomarker discovery through proteomics

    NARCIS (Netherlands)

    Barasa, B.A.; Slijper, M.

    2014-01-01

    Red blood cells are rather unique body cells, since they have lost all organelles when mature, which results in lack of potential to replace proteins that have lost their function. They maintain only a few pathways for obtaining energy and reducing power for the key functions they need to fulfill. T

  3. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.

    Science.gov (United States)

    Salzer, Elisabeth; Santos-Valente, Elisangela; Klaver, Stefanie; Ban, Sol A; Emminger, Wolfgang; Prengemann, Nina Kathrin; Garncarz, Wojciech; Müllauer, Leonhard; Kain, Renate; Boztug, Heidrun; Heitger, Andreas; Arbeiter, Klaus; Eitelberger, Franz; Seidel, Markus G; Holter, Wolfgang; Pollak, Arnold; Pickl, Winfried F; Förster-Waldl, Elisabeth; Boztug, Kaan

    2013-04-18

    Primary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family suffering from recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, a defective class switch indicated by low numbers of IgM- and IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase δ (PRKCD), causing the absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate was decreased, and mRNA levels of nuclear factor interleukin (IL)-6 and IL-6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B-cell deficiency with severe autoimmunity.

  4. Computational modeling of red blood cells: A symplectic integration algorithm

    Science.gov (United States)

    Schiller, Ulf D.; Ladd, Anthony J. C.

    2010-03-01

    Red blood cells can undergo shape transformations that impact the rheological properties of blood. Computational models have to account for the deformability and red blood cells are often modeled as elastically deformable objects. We present a symplectic integration algorithm for deformable objects. The surface is represented by a set of marker points obtained by surface triangulation, along with a set of fiber vectors that describe the orientation of the material plane. The various elastic energies are formulated in terms of these variables and the equations of motion are obtained by exact differentiation of a discretized Hamiltonian. The integration algorithm preserves the Hamiltonian structure and leads to highly accurate energy conservation, hence he method is expected to be more stable than conventional finite element methods. We apply the algorithm to simulate the shape dynamics of red blood cells.

  5. Prolonged storage of packed red blood cells for blood transfusion.

    Science.gov (United States)

    Martí-Carvajal, Arturo J; Simancas-Racines, Daniel; Peña-González, Barbra S

    2015-07-14

    A blood transfusion is an acute intervention, used to address life- and health-threatening conditions on a short-term basis. Packed red blood cells are most often used for blood transfusion. Sometimes blood is transfused after prolonged storage but there is continuing debate as to whether transfusion of 'older' blood is as beneficial as transfusion of 'fresher' blood. To assess the clinical benefits and harms of prolonged storage of packed red blood cells, in comparison with fresh, on recipients of blood transfusion. We ran the search on 1st May 2014. We searched the Cochrane Injuries Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO Host) and two other databases. We also searched clinical trials registers and screened reference lists of the retrieved publications and reviews. We updated this search in June 2015 but these results have not yet been incorporated. Randomised clinical trials including participants assessed as requiring red blood cell transfusion were eligible for inclusion. Prolonged storage was defined as red blood cells stored for ≥ 21 days in a blood bank. We did not apply limits regarding the duration of follow-up, or country where the study took place. We excluded trials where patients received a combination of short- and long-stored blood products, and also trials without a clear definition of prolonged storage. We independently performed study selection, risk of bias assessment and data extraction by at least two review authors. The major outcomes were death from any cause, transfusion-related acute lung injury, and adverse events. We estimated relative risk for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. We identified three randomised clinical trials, involving a total of 120 participants, comparing packed red blood cells with ≥ 21 days storage

  6. Clinical experience in T cell deficient patients

    Directory of Open Access Journals (Sweden)

    Cole Theresa S

    2010-05-01

    Full Text Available Abstract T cell disorders have been poorly understood until recently. Lack of knowledge of underlying molecular mechanisms together with incomplete data on long term outcome have made it difficult to assess prognosis and give the most effective treatment. Rapid progress in defining molecular defects, improved supportive care and much improved results from hematopoietic stem cell transplantation (HSCT now mean that curative treatment is possible for many patients. However, this depends on prompt recognition, accurate diagnosis and careful treatment planning. This review will discuss recent progress in our clinical and molecular understanding of a variety of disorders including: severe combined immunodeficiency, specific T cell immunodeficiencies, signaling defects, DNA repair defects, immune-osseous dysplasias, thymic disorders and abnormalities of apoptosis. There is still much to discover in this area and some conditions which are as yet very poorly understood. However, with increased knowledge about how these disorders can present and the particular problems each group may face it is hoped that these patients can be recognized early and managed appropriately, so providing them with the best possible outcome.

  7. In HepG2 Cells, Coexisting Carnitine Deficiency Masks Important Indicators of Marginal Biotin Deficiency123

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    Background: A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. Objective: In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. Methods: We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography–tandem mass spectrometry. Results: Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased

  8. Photoacoustic response of suspended and hemolyzed red blood cells

    Science.gov (United States)

    Saha, Ratan K.; Karmakar, Subhajit; Roy, Madhusudan

    2013-07-01

    The effect of confinement of hemoglobin molecules on photoacoustic (PA) signal is studied experimentally. The PA amplitudes for samples with suspended red blood cells (SRBCs) and hemolyzed red blood cells (HRBCs) were found to be comparable at each hematocrit for 532 nm illumination. The difference between the corresponding amplitudes increased with increasing hematocrit for 1064 nm irradiation. For example, the PA amplitude for the SRBCs was about 260% higher than that of the HRBCs at 40% hematocrit. This observation may help to develop a PA method detecting hemolysis noninvasively.

  9. Deep coverage mouse red blood cell proteome: a first comparison with the human red blood cell.

    Science.gov (United States)

    Pasini, Erica M; Kirkegaard, Morten; Salerno, Doris; Mortensen, Peter; Mann, Matthias; Thomas, Alan W

    2008-07-01

    Mice have close genetic/physiological relationships to humans, breed rapidly, and can be genetically modified, making them the most used mammal in biomedical research. Because the red blood cell (RBC) is the sole gas transporter in vertebrates, diseases of the RBC are frequently severe; much research has therefore focused on RBC and cardiovascular disorders of mouse and humans. RBCs also host malaria parasites. Recently we presented an in-depth proteome for the human RBC. Here we present directly comparable data for the mouse RBC as membrane-only, soluble-only, and combined membrane-bound/soluble proteomes (comprising, respectively, 247, 232, and 165 proteins). All proteins were identified, validated, and categorized in terms of subcellular localization, protein family, and function, and in comparison with the human RBC, were classified as orthologs, family-related, or unique. Splice isoforms were identified, and polypeptides migrating with anomalous apparent molecular weights were grouped into putatively ubiquitinated or partially degraded complexes. Overall there was close concordance between mouse and human proteomes, confirming the unexpected RBC complexity. Several novel findings in the human proteome have been confirmed here. This comparison sheds light on several open issues in RBC biology and provides a departure point for more comprehensive understanding of RBC function.

  10. Apoptosis and signalling in acid sphingomyelinase deficient cells

    Directory of Open Access Journals (Sweden)

    Sillence Dan J

    2001-11-01

    Full Text Available Abstract Background Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid induces blebbing of the plasma membrane to aid rapid engulfment by professional phagocytes. However contrary evidence suggests that cells which are deficient in acid sphingomyelinase are defective in apoptosis signalling. This data has been interpreted as support for the activation of acid sphingomyelinase as an early signal in apoptosis. Hypothesis An alternative explanation is put forward whereby the accumulation of intracellular sphingomyelin in sphingomyelinase deficient cells leads to the formation of intracellular rafts which lead to the sequestration of important signalling molecules that are normally present on the cell surface where they perform their function. Testing the hypothesis It is expected that the subcellular distribution of important signalling molecules is altered in acid sphingomyelinase deficient cells, leading to their sequestration in late endosomes / lysosomes. Other sphingolipid storage diseases such as Niemann-Pick type C which have normal acid sphingomyelinase activity would also be expected to show the same phenotype. Implications of the hypothesis If true the hypothesis would provide a mechanism for the pathology of the sphingolipid storage diseases at the cellular level and also have implications for the role of ceramide in apoptosis.

  11. Squeezing red blood cells on an optical waveguide to monitor cell deformability during blood storage.

    Science.gov (United States)

    Ahluwalia, Balpreet Singh; McCourt, Peter; Oteiza, Ana; Wilkinson, James S; Huser, Thomas R; Hellesø, Olav Gaute

    2015-01-07

    Red blood cells squeeze through micro-capillaries as part of blood circulation in the body. The deformability of red blood cells is thus critical for blood circulation. In this work, we report a method to optically squeeze red blood cells using the evanescent field present on top of a planar waveguide chip. The optical forces from a narrow waveguide are used to squeeze red blood cells to a size comparable to the waveguide width. Optical forces and pressure distributions on the cells are numerically computed to explain the squeezing process. The proposed technique is used to quantify the loss of blood deformability that occurs during blood storage lesion. Squeezing red blood cells using waveguides is a sensitive technique and works simultaneously on several cells, making the method suitable for monitoring stored blood.

  12. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  13. Fermented red ginseng extract inhibits cancer cell proliferation and viability.

    Science.gov (United States)

    Oh, Jisun; Jeon, Seong Bin; Lee, Yuri; Lee, Hyeji; Kim, Ju; Kwon, Bo Ra; Yu, Kang-Yeol; Cha, Jeong-Dan; Hwang, Seung-Mi; Choi, Kyung-Min; Jeong, Yong-Seob

    2015-04-01

    Red ginseng (Panax ginseng C.A. Meyer) is the most widely recognized medicinal herb due to its remedial effects in various disorders, such as cancers, diabetes, and heart problems. In this study, we investigated the anticancer effect of fermented red ginseng extract (f-RGE; provided by Jeonju Biomaterials Institute, Jeonju, South Korea) in a parallel comparison with the effect of nonfermented red ginseng extract (nf-RGE; control) on several cancer cell lines--MCF-7 breast cancer cells, HepG2 hepatocellular carcinoma cells, and reprogrammed MCF-7 cells (mimicking cancer stem cells). Cells were cultured at various concentrations of RGE (from 0.5 up to 5 mg/mL) and their viabilities and proliferative properties were examined. Our data demonstrate the following: (1) nf-RGE inhibited cell viability at ≥1 mg/mL for MCF-7 cells and ≥2 mg/mL for HepG2 cells, (2) in the presence of a carcinogenic agent, 12-O-tetradecanoylphorbol-13-acetate (TPA), nf-RGE treatment in combination with paclitaxel synergistically decreased MCF-7 as well as HepG2 cell viability, (3) f-RGE (which contained a greater level of Rg3 content) more effectively decreased the viability of MCF-7 and HepG2 cells compared to nf-RGE, and (4) f-RGE appeared more potent for inhibiting cancerous differentiation of reprogrammed MCF-7 cells in a synergistic fashion with paclitaxel, especially in the presence of TPA, compared to nf-RGE. These findings suggest that f-RGE treatment may be more effective for decreasing cancer cell survival by inducing apoptotic cell death and also presumably for preventing cancer stem cell differentiation compared to nf-RGE.

  14. [Hereditary red cell membrane disorders in Japan: comparison with other countries].

    Science.gov (United States)

    Nakanishi, Hidekazu; Wada, Hideho; Suemori, Shinichiro; Sugihara, Takashi

    2015-07-01

    Red cell membrane disorders are the most common type of inherited hemolytic disorders in the Japanese population. In hereditary spherocytosis (HS), the primary presentation is a loss of membrane surface area, leading to reduced deformability because of defects in the membrane proteins ankyrin, band 3, β-spectrin, α spectrin, or protein 4.2 (P4.2). Complete P4.2 deficiencies, which are inherited in an autosomal recessive manner, comprise a unique HS subgroup and are common in Japanese, but rare in other populations. In contrast, the principle presentation in hereditary elliptocytosis (HE) is mechanical weakness of the erythrocyte membrane skeleton due to defects in α-spectrin, β-spectrin, or protein 4.1. Although α-spectrin mutations are the most frequent cause of HE in Caucasian, African, and Mediterranean populations, these mutations are rare in the Japanese population, in which P4.1 deficiencies are instead most common. Furthermore, hereditary stomatocytoses (HSt) are disorders of monovalent cation permeability in the red cell membrane.

  15. Novel type of red blood cell pyruvate kinase hyperactivity predicts a remote regulatory locus involved in PKLR gene expression.

    Science.gov (United States)

    van Oirschot, Brigitte Antoinette; Francois, Jerney Johanna Jeanette Maria; van Solinge, Wouter Willem; van Wesel, Annet Cornelia Wilhelmina; Rijksen, Gert; van Amstel, Hans Kristian Ploos; van Wijk, Richard

    2014-04-01

    Red blood cell pyruvate kinase (PK-R) is a key regulatory enzyme of red cell metabolism. Hereditary deficiency of PK-R is caused by mutations in the PKLR gene, leading to chronic nonspherocytic hemolytic anemia. In contrast to PK deficiency, inherited PK hyperactivity has also been described. This very rare abnormality of RBC metabolism has been documented in only two families and appears to be without clinical consequences. Thus far, it has been attributed to either a gain of function mutation in PKLR or to persistent expression of the fetal PK isozyme PK-M2 in mature red blood cells. We here report on a novel type of inherited PK hyperactivity that is characterized by solely increased expression of a kinetically normal PK-R. In line with the latter, no mutations were detected in PKLR. Mutations in regulatory regions as well as variations in PKLR copy number were also absent. In addition, linkage analysis suggested that PK hyperactivity segregated independently from the PKLR locus. We therefore postulate that the causative mutation resides in a novel yet-unidentified locus, and upregulates PKLR gene expression. Other mutations of the same locus may be involved in those cases of PK deficiency that fail to reveal mutations in PKLR.

  16. Deoxygenation affects tyrosine phosphoproteome of red cell membrane from patients with sickle cell disease.

    Science.gov (United States)

    Siciliano, Angela; Turrini, Franco; Bertoldi, Mariarita; Matte, Alessandro; Pantaleo, Antonella; Olivieri, Oliviero; De Franceschi, Lucia

    2010-04-15

    Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder related to the production of a defective form of hemoglobin, hemoglobin S (HbS). One of the hallmarks of SCD is the presence of dense, dehydrate highly adhesive sickle red blood cells (RBCs) that result from persistent membrane damage associated with HbS polymerization, abnormal activation of membrane cation transports and generation of distorted and rigid red cells with membrane perturbation and cytoskeleton dysfunction. Although modulation of phosphorylation state of the proteins from membrane and cytoskeleton networks has been proposed to participate in red cell homeostasis, much still remains to be investigated in normal and diseased red cells. Here, we report that tyrosine (Tyr-) phosphoproteome of sickle red cells was different from normal controls and was affected by deoxygenation. We found proteins, p55 and band 4.1, from the junctional complex, differently Tyr-phosphorylated in SCD RBCs compared to normal RBCs under normoxia and modulated by deoxygenation, while band 4.2 was similarly Tyr-phosphorylated in both conditions. In SCD RBCs we identified the phosphopeptides for protein 4.1R located in the protein FERM domain (Tyr-13) and for alpha-spectrin located near or in a linker region (Tyr-422 and Tyr-1498) involving protein areas crucial for their functions in the context of red cell membrane properties, suggesting that Tyr-phosphorylation may be part of the events involved in maintaining membrane mechanical stability in SCD red cells.

  17. Role of Complement in Red Cell Dysfunction in Trauma

    Science.gov (United States)

    2013-12-01

    such as in systemic lupus erythematosus (SLE), complement fragments deposit on the surface of red blood cells (RBC), which limits their...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information . Send comments

  18. The effects of cryopreservation on red blood cell rheologic properties

    NARCIS (Netherlands)

    Henkelman, Sandra; Lagerberg, Johan W. M.; Graaff, Reindert; Rakhorst, Gerhard; van Oeveren, Willem

    2010-01-01

    BACKGROUND: In transfusion medicine, frozen red blood cells (RBCs) are an alternative for liquid-stored RBCs. Little is known about the rheologic properties (i.e., aggregability and deformability) of thawed RBCs. In this study the rheologic properties of high-glycerol frozen RBCs and postthaw stored

  19. Red blood cells intended for transfusion : quality criteria revisited

    NARCIS (Netherlands)

    Hogman, CF; Meryman, HT

    2006-01-01

    Great variation exists with respect to viability and function of fresh and stored red blood cells (RBCs) as well as of the contents of RBC hemoglobin (Hb) in individual units. Improved technology is available for the preparation as well as the storage of RBCs. The authors raise the question whether

  20. Hypoxia, hormones, and red blood cell function in chick embryos.

    Science.gov (United States)

    Dragon, Stefanie; Baumann, Rosemarie

    2003-04-01

    The red blood cell function of avian embryos is regulated by cAMP. Adenosine A(2A) and beta-adrenergic receptor activation during hypoxic conditions cause changes in the hemoglobin oxygen affinity and CO(2) transport. Furthermore, experimental evidence suggests a general involvement of cAMP in terminal differentiation of avian erythroblasts.

  1. Red blood cell transfusion during septic shock in the ICU

    DEFF Research Database (Denmark)

    Perner, A; Smith, S H; Carlsen, S

    2012-01-01

    Transfusion of red blood cells (RBCs) remains controversial in patients with septic shock, but current practice is unknown. Our aim was to evaluate RBC transfusion practice in septic shock in the intensive care unit (ICU), and patient characteristics and outcome associated with RBC transfusion....

  2. Spatial distributions of red blood cells significantly alter local haemodynamics.

    Directory of Open Access Journals (Sweden)

    Joseph M Sherwood

    Full Text Available Although bulk changes in red blood cell concentration between vessels have been well characterised, local distributions are generally overlooked. Red blood cells aggregate, deform and migrate within vessels, forming heterogeneous distributions which have considerable effect on local haemodynamics. The present study reports data on the local distribution of human red blood cells in a sequentially bifurcating microchannel, representing the branching geometry of the microvasculature. Imaging methodologies with simple extrapolations are used to infer three dimensional, time-averaged velocity and haematocrit distributions under a range of flow conditions. Strong correlation between the bluntness of the velocity and haematocrit profiles in the parent branch of the geometry is observed and red blood cell aggregation has a notable effect on the observed trends. The two branches of the first bifurcation show similar characteristics in terms of the shapes of the profiles and the extent of plasma skimming, despite the difference in geometric configuration. In the second bifurcation, considerable asymmetry between the branches in the plasma skimming relationship is observed, and elucidated by considering individual haematocrit profiles. The results of the study highlight the importance of considering local haematocrit distributions in the analysis of blood flow and could lead to more accurate computational models of blood flow in microvascular networks. The experimental approaches developed in this work provide a foundation for further examining the characteristics of microhaemodynamics.

  3. Red blood cell antibodies in pregnancy and their clinical consequences

    DEFF Research Database (Denmark)

    Nordvall, Maria; Dziegiel, Morten Hanefeld; Hegaard, Hanne Kristine;

    2009-01-01

    The objective was to determine clinical consequences of various specificities for the infant/fetus. The population was patients referred between 1998 and 2005 to the tertiary center because of detected red blood cell (RBC) alloimmunization. Altogether 455 infants were delivered by 390 alloimmunized...

  4. Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

    NARCIS (Netherlands)

    Darghouth, D.; Koehl, B.; Heilier, J.F.; Madalinski, G.; Bovee, P.H.; Bosman, G.J.C.G.M.; Delaunay, J.; Junot, C.; Romeo, P.H.

    2011-01-01

    Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this

  5. Sodium renders endothelial cells sticky for red blood cells

    Directory of Open Access Journals (Sweden)

    Hans eOberleithner

    2015-06-01

    Full Text Available Negative charges in the glycocalyx of red blood cells (RBC and vascular endothelial cells (EC facilitate frictionless blood flow through blood vessels. Na+ selectively shields these charges controlling surface electronegativity. The question was addressed whether the ambient Na+ concentration controls RBC-EC interaction. Using atomic force microscopy (AFM adhesion forces between RBC and endothelial glycocalyx were quantified. A single RBC, mounted on an AFM cantilever, was brought in physical contact with the endothelial surface and then pulled off. Adhesion forces were quantified (i after enzymatic removal of negative charges in the glycocalyx, (ii under different ambient Na+ and (iii after applying the intracellular aldosterone receptor antagonist spironolactone. Removal of negative surface charges increases RBC-EC interaction forces. A stepwise increase of ambient Na+ from 133 to 140 mM does not affect them. However, beyond 140 mM Na+ adhesion forces increase sharply (10% increase of adhesion force per 1 mM increase of Na+. Spironolactone prevents this response. It is concluded that negative charges reduce adhesion between RBC and EC. Ambient Na+ concentration determines the availability of free negative charges. Na+ concentrations in the low physiological range (below 140 mM allow sufficient amounts of vacant negative charges so that adhesion of RBC to the endothelial surface is small. In contrast, Na+ in the high physiological range (beyond 140 mM saturates the remaining negative surface charges thus increasing adhesion. Aldosterone receptor blockade by spironolactone prevents Na+ induced RBC adhesion to the endothelial glycocalyx. Extrapolation of in vitro experiments to in vivo conditions leads to the hypothesis that high sodium intake is likely to increase the incidence of thrombotic events.

  6. Sodium renders endothelial cells sticky for red blood cells.

    Science.gov (United States)

    Oberleithner, Hans; Wälte, Mike; Kusche-Vihrog, Kristina

    2015-01-01

    Negative charges in the glycocalyx of red blood cells (RBC) and vascular endothelial cells (EC) facilitate frictionless blood flow through blood vessels. Na(+) selectively shields these charges controlling surface electronegativity. The question was addressed whether the ambient Na(+) concentration controls RBC-EC interaction. Using atomic force microscopy (AFM) adhesion forces between RBC and endothelial glycocalyx were quantified. A single RBC, mounted on an AFM cantilever, was brought in physical contact with the endothelial surface and then pulled off. Adhesion forces were quantified (i) after enzymatic removal of negative charges in the glycocalyx, (ii) under different ambient Na(+) and (iii) after applying the intracellular aldosterone receptor antagonist spironolactone. Removal of negative surface charges increases RBC-EC interaction forces. A stepwise increase of ambient Na(+) from 133 to 140 mM does not affect them. However, beyond 140 mM Na(+) adhesion forces increase sharply (10% increase of adhesion force per 1 mM increase of Na(+)). Spironolactone prevents this response. It is concluded that negative charges reduce adhesion between RBC and EC. Ambient Na(+) concentration determines the availability of free negative charges. Na(+) concentrations in the low physiological range (below 140 mM) allow sufficient amounts of vacant negative charges so that adhesion of RBC to the endothelial surface is small. In contrast, Na(+) in the high physiological range (beyond 140 mM) saturates the remaining negative surface charges thus increasing adhesion. Aldosterone receptor blockade by spironolactone prevents Na(+) induced RBC adhesion to the endothelial glycocalyx. Extrapolation of in vitro experiments to in vivo conditions leads to the hypothesis that high sodium intake is likely to increase the incidence of thrombotic events.

  7. Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Filosa, S.; Giacometti, N.; Wangwei, C.; Martini, G. [Istituto Internazionale di Genetica e Biofisica, Naples (Italy)] [and others

    1996-10-01

    X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G{r_arrow}A) and two with G6PD Bari (1187C{r_arrow}T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis. 65 refs., 6 figs., 3 tabs.

  8. Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

    Directory of Open Access Journals (Sweden)

    Biljana Musicki

    Full Text Available Testosterone deficiency is associated with sickle cell disease (SCD, but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH levels compared with wild type (WT mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR, but not cholesterol side-chain cleavage enzyme (P450scc, in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

  9. Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

    Science.gov (United States)

    Musicki, Biljana; Zhang, Yuxi; Chen, Haolin; Brown, Terry R; Zirkin, Barry R; Burnett, Arthur L

    2015-01-01

    Testosterone deficiency is associated with sickle cell disease (SCD), but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle) exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH) levels compared with wild type (WT) mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol)- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR), but not cholesterol side-chain cleavage enzyme (P450scc), in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi) exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

  10. Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies

    Directory of Open Access Journals (Sweden)

    Michel Haagdorens

    2016-01-01

    Full Text Available Severe ocular surface disease can result in limbal stem cell deficiency (LSCD, a condition leading to decreased visual acuity, photophobia, and ocular pain. To restore the ocular surface in advanced stem cell deficient corneas, an autologous or allogenic limbal stem cell transplantation is performed. In recent years, the risk of secondary LSCD due to removal of large limbal grafts has been significantly reduced by the optimization of cultivated limbal epithelial transplantation (CLET. Despite the great successes of CLET, there still is room for improvement as overall success rate is 70% and visual acuity often remains suboptimal after successful transplantation. Simple limbal epithelial transplantation reports higher success rates but has not been performed in as many patients yet. This review focuses on limbal epithelial stem cells and the pathophysiology of LSCD. State-of-the-art therapeutic management of LSCD is described, and new and evolving techniques in ocular surface regeneration are being discussed, in particular, advantages and disadvantages of alternative cell scaffolds and cell sources for cell based ocular surface reconstruction.

  11. Macromolecular Dynamics in Red Blood Cells Investigated Using Neutron Spectroscopy

    CERN Document Server

    Stadler, Andreas Maximilian; Demmel, Franz; Artmann, Gerhard; 10.1098/rsif.2010.0306

    2011-01-01

    We present neutron scattering measurements on the dynamics of hemoglobin (Hb) in human red blood cells in vivo. Global and internal Hb dynamics were measured in the ps to ns time- and {\\AA} length-scale using quasielastic neutron backscattering spectroscopy. We observed the cross-over from global Hb short-time to long-time self-diffusion. Both short- and long-time diffusion coefficients agree quantitatively with predicted values from hydrodynamic theory of non-charged hard-sphere suspensions when a bound water fraction of around 0.23g H2O/ g Hb is taken into account. The higher amount of water in the cells facilitates internal protein fluctuations in the ps time-scale when compared to fully hydrated Hb powder. Slower internal dynamics of Hb in red blood cells in the ns time-range were found to be rather similar to results obtained with fully hydrated protein powders, solutions and E. coli cells.

  12. Aggregation of Red Blood Cells: From Rouleaux to Clot Formation

    CERN Document Server

    Wagner, C; Svetina, S

    2013-01-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the binding mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the binding strength. Another important aggregation mechanism is caused by activation of platelets. This leads to clot formation which is life saving in the case of wound healing but also a major cause of death in the case of a thrombus induced stroke. We review historical and recent results on the participation of red blood cells in clot formation.

  13. Engineering of red cells of Arabidopsis thaliana and comparative genome-wide gene expression analysis of red cells versus wild-type cells.

    Science.gov (United States)

    Shi, Ming-Zhu; Xie, De-Yu

    2011-04-01

    We report metabolic engineering of Arabidopsis red cells and genome-wide gene expression analysis associated with anthocyanin biosynthesis and other metabolic pathways between red cells and wild-type (WT) cells. Red cells of A. thaliana were engineered for the first time from the leaves of production of anthocyanin pigment 1-Dominant (pap1-D). These red cells produced seven anthocyanin molecules including a new one that was characterized by LC-MS analysis. Wild-type cells established as a control did not produce anthocyanins. A genome-wide microarray analysis revealed that nearly 66 and 65% of genes in the genome were expressed in the red cells and wild-type cells, respectively. In comparison with the WT cells, 3.2% of expressed genes in the red cells were differentially expressed. The expression levels of 14 genes involved in the biosynthetic pathway of anthocyanin were significantly higher in the red cells than in the WT cells. Microarray and RT-PCR analyses demonstrated that the TTG1-GL3/TT8-PAP1 complex regulated the biosynthesis of anthocyanins. Furthermore, most of the genes with significant differential expression levels in the red cells versus the WT cells were characterized with diverse biochemical functions, many of which were mapped to different metabolic pathways (e.g., ribosomal protein biosynthesis, photosynthesis, glycolysis, glyoxylate metabolism, and plant secondary metabolisms) or organelles (e.g., chloroplast). We suggest that the difference in gene expression profiles between the two cell lines likely results from cell types, the overexpression of PAP1, and the high metabolic flux toward anthocyanins.

  14. Red blood cell and iron metabolism during space flight

    Science.gov (United States)

    Smith, Scott M.

    2002-01-01

    Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood.

  15. Shear stress-induced improvement of red blood cell deformability

    OpenAIRE

    Meram, Ece; Yılmaz, Bahar D.; Bas, Ceren; Atac, Nazlı; Yalçın, Ö.; Başkurt, Oguz K.; Meiselman, Herbert J.

    2013-01-01

    Classically, it is known that red blood cell (RBC) deformability is determined by the geometric and material properties of these cells. Experimental evidence accumulated during the last decade has introduced the concept of active regulation of RBC deformability. This regulation is mainly related to altered associations between membrane skeletal proteins and integral proteins, with the latter serving to anchor the skeleton to the lipid matrix. It has been hypothesized that shear stress induces...

  16. Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection

    Directory of Open Access Journals (Sweden)

    McCall Matthew

    2010-06-01

    Full Text Available Abstract Background An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies. Methods Peripheral blood mononuclear cells from Tanzanian preschool children were stimulated in vitro with Plasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status. Results The data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-γ response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-γ production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status. Conclusions The pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status.

  17. The red cell storage lesion(s): of dogs and men

    Science.gov (United States)

    Klein, Harvey G.

    2017-01-01

    The advent of preservative solutions permitted refrigerated storage of red blood cells. However, the convenience of having red blood cell inventories was accompanied by a disadvantage. Red cells undergo numerous physical and metabolic changes during cold storage, the “storage lesion(s)”. Whereas controlled clinical trials have not confirmed the clinical importance of such changes, ethical and operational issues have prevented careful study of the oldest stored red blood cells. Suggestions of toxicity from meta-analyses motivated us to develop pre-clinical canine models to compare the freshest vs the oldest red blood cells. Our model of canine pneumonia with red blood cell transfusion indicated that the oldest red blood cells increased mortality, that the severity of pneumonia is important, but that the dose of transfused red blood cells is not. Washing the oldest red blood cells reduces mortality by removing senescent cells and remnants, whereas washing fresher cells increases mortality by damaging the red blood cell membrane. An opposite effect was found in a model of haemorrhagic shock with reperfusion injury. Physiological studies indicate that release of iron from old cells is a primary mechanism of toxicity during infection, whereas scavenging of cell-free haemoglobin may be beneficial during reperfusion injury. Intravenous iron appears to have toxicity equivalent to old red blood cells in the pneumonia model, suggesting that intravenous iron and old red blood cells should be administered with caution to infected patients. PMID:28263166

  18. Mechanopathology of red blood cell diseases—Why mechanics matters

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular structures.These alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape,deformability and adhesion.As such,knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ones.Here,we will present biomechanistic insights into red blood cell related diseases that manifest...

  19. Backward elastic light scattering of malaria infected red blood cells

    Science.gov (United States)

    Lee, Seungjun; Lu, Wei

    2011-08-01

    We investigated the backward light scattering pattern of healthy and malaria (Plasmodium falciparum) parasitized red blood cells. The spectrum could clearly distinguish between predominant ring stage infected blood cells and healthy blood cells. Further, we found that infected samples mixed with different stages of P. falciparum showed different signals, suggesting that even variance in parasite stages could also be detected by the spectrum. These results together with the backward scattering technique suggest the potential of non-invasive diagnosis of malaria through light scattering of blood cells near the surface of human body, such as using eyes or skin surface.

  20. Characterization of dsRed2-positive cells in the doublecortin-dsRed2 transgenic adult rat retina.

    Science.gov (United States)

    Trost, A; Schroedl, F; Marschallinger, J; Rivera, F J; Bogner, B; Runge, C; Couillard-Despres, S; Aigner, L; Reitsamer, H A

    2014-12-01

    Doublecortin (DCX) is predominantly expressed in neuronal precursor cells and young immature neurons of the developing and adult brain, where it is involved in neuronal differentiation, migration and plasticity. Moreover, its expression pattern reflects neurogenesis, and transgenic DCX promoter-driven reporter models have been previously used to investigate adult neurogenesis. In this study, we characterize dsRed2 reporter protein-expressing cells in the adult retina of the transgenic DCX promoter-dsRed2 rat model, with the aim to identify cells with putative neurogenic activity. Additionally, we confirmed the expression of the dsRed2 protein in DCX-expressing cells in the adult hippocampal dentate gyrus. Adult DCX-dsRed2 rat retinas were analyzed by immunohistochemistry for expression of DCX, NF200, Brn3a, Sox2, NeuN, calbindin, calretinin, PKC-a, Otx2, ChAT, PSA-NCAM and the glial markers GFAP and CRALBP, followed by confocal laser-scanning microscopy. In addition, brain sections of transgenic rats were analyzed for dsRed2 expression and co-localization with DCX, NeuN, GFAP and Sox2 in the cortex and dentate gyrus. Endogenous DCX expression in the adult retina was confined to horizontal cells, and these cells co-expressed the DCX promoter-driven dsRed2 reporter protein. In addition, we encountered dsRed2 expression in various other cell types in the retina: retinal ganglion cells (RGCs), a subpopulation of amacrine cells, a minority of bipolar cells and in perivascular cells. Since also RGCs expressed dsRed2, the DCX-dsRed2 rat model might offer a useful tool to study RGCs in vivo under various conditions. Müller glial cells, which have previously been identified as cells with stem cell features and with neurogenic potential, did express neither endogenous DCX nor the dsRed2 reporter. However, and surprisingly, we identified a perivascular glial cell type expressing the dsRed2 reporter, enmeshed with the glia/stem cell marker GFAP and colocalizing with the

  1. Membranotropic photobiomodulation on red blood cell deformability

    Science.gov (United States)

    Luo, Gang-Yue; Zhao, Yan-Ping; Liu, Timon C.; Liu, Song-Hao

    2007-05-01

    To assess modulation of laser on erythrocyte permeability and deformability via cell morphology changes, healthy human echinocytes with shrinking size and high plasmic viscosity due to cellular dehydration were treated with 1 mW, 2 mW, 3 mW, and 5 mW laser power exposure respectively. Image analyzing system on single intact erythrocyte was applied for measuring comprehensive cell morphological parameters (surface area, external membrane perimeter, circle index and elongation index) that were determined by the modulation of erythrocyte water permeability and deformability to detect relationship between erythrocyte water permeability alteration and deformability. Our preliminary experiment showed that exposure under light dose of 5 mW for 5 min could induce more active erythrocyte swelling and deformation. water channel aquaporin-1(AQP-1) was inhibited by the incubation of HgCl II in the presence and absence of 5 mW laser irradiation. The result suggested that osmotic water permeability is a primary factor in the procedure of erythrocyte deformability. In addition, no modulation of laser(5mW) on erythrocyte deformability had been found when the echinocytes were cultured with GDP-β-S (G protein inhibitor).

  2. Partitioning of red blood cell aggregates in bifurcating microscale flows

    Science.gov (United States)

    Kaliviotis, E.; Sherwood, J. M.; Balabani, S.

    2017-03-01

    Microvascular flows are often considered to be free of red blood cell aggregates, however, recent studies have demonstrated that aggregates are present throughout the microvasculature, affecting cell distribution and blood perfusion. This work reports on the spatial distribution of red blood cell aggregates in a T-shaped bifurcation on the scale of a large microvessel. Non-aggregating and aggregating human red blood cell suspensions were studied for a range of flow splits in the daughter branches of the bifurcation. Aggregate sizes were determined using image processing. The mean aggregate size was marginally increased in the daughter branches for a range of flow rates, mainly due to the lower shear conditions and the close cell and aggregate proximity therein. A counterintuitive decrease in the mean aggregate size was apparent in the lower flow rate branches. This was attributed to the existence of regions depleted by aggregates of certain sizes in the parent branch, and to the change in the exact flow split location in the T-junction with flow ratio. The findings of the present investigation may have significant implications for microvascular flows and may help explain why the effects of physiological RBC aggregation are not deleterious in terms of in vivo vascular resistance.

  3. Nature of the elements transporting long-chain fatty acids through the red cell membrane

    DEFF Research Database (Denmark)

    Bojesen, Inge Norby; Bojesen, Eigil

    1998-01-01

    Docosahexaenoic acid, linoleic acid, red cell membrane, transporting elements, transport kinetics, fatty acid transport......Docosahexaenoic acid, linoleic acid, red cell membrane, transporting elements, transport kinetics, fatty acid transport...

  4. A comparison of retinyl palmitate and red palm oil β-carotene as strategies to address Vitamin A deficiency.

    Science.gov (United States)

    Souganidis, Ellie; Laillou, Arnaud; Leyvraz, Magali; Moench-Pfanner, Regina

    2013-08-15

    Vitamin A deficiency continues to be an international public health problem with several important health consequences including blindness and overall increased rates of morbidity and mortality. To address this widespread issue, a series of strategies have been put into place from dietary diversification to supplementation and fortification programs. Retinyl palmitate has been used successfully for decades as a supplement as well as a way to fortify numerous foods, including vegetable oil, rice, monosodium glutamate, cereal flours and sugar. Recently, there has been rising interest in using a natural source of carotenoids, β-carotene from red palm oil (RPO), for fortification. Although RPO interventions have also been shown to effectively prevent Vitamin A deficiency, there are numerous challenges in using beta-carotene from RPO as a fortification technique. β-Carotene can induce significant changes in appearance and taste of the fortified product. Moreover, costs of fortifying with beta-carotene are higher than with retinyl palmitate. Therefore, RPO should only be used as a source of Vitamin A if it is produced and used in its crude form and regularly consumed without frying. Furthermore, refined RPO should be fortified with retinyl palmitate, not β-carotene, to ensure that there is adequate Vitamin A content.

  5. A Comparison of Retinyl Palmitate and Red Palm Oil β-Carotene as Strategies to Address Vitamin A Deficiency

    Directory of Open Access Journals (Sweden)

    Regina Moench-Pfanner

    2013-08-01

    Full Text Available Vitamin A deficiency continues to be an international public health problem with several important health consequences including blindness and overall increased rates of morbidity and mortality. To address this widespread issue, a series of strategies have been put into place from dietary diversification to supplementation and fortification programs. Retinyl palmitate has been used successfully for decades as a supplement as well as a way to fortify numerous foods, including vegetable oil, rice, monosodium glutamate, cereal flours and sugar. Recently, there has been rising interest in using a natural source of carotenoids, β-carotene from red palm oil (RPO, for fortification. Although RPO interventions have also been shown to effectively prevent Vitamin A deficiency, there are numerous challenges in using beta-carotene from RPO as a fortification technique. β-Carotene can induce significant changes in appearance and taste of the fortified product. Moreover, costs of fortifying with beta-carotene are higher than with retinyl palmitate. Therefore, RPO should only be used as a source of Vitamin A if it is produced and used in its crude form and regularly consumed without frying. Furthermore, refined RPO should be fortified with retinyl palmitate, not β-carotene, to ensure that there is adequate Vitamin A content.

  6. Phosphorus deficiency in red clover promotes exudation of orobanchol, the signal for mycorrhizal symbionts and germination stimulant for root parasites.

    Science.gov (United States)

    Yoneyama, Kaori; Yoneyama, Koichi; Takeuchi, Yasutomo; Sekimoto, Hitoshi

    2007-03-01

    Plant derived sesquiterpene strigolactones, which have previously been characterized as germination stimulants for root parasitic plants, have recently been identified as the branching factors which induce hyphal branching morphogenesis, a critical step in host recognition by arbuscular mycorrhizal (AM) fungi. We show here that, in red clover plants (Trifolium pratense L.), which is known as a host for both AM fungi and the root holoparasitic plant Orobanche minor Sm., reduced supply of phosphorus (P) but not of other elements examined (N, K, Mg, Ca) in the culture medium significantly promotes the release of a strigolactone, orobanchol, by the roots of this plant. In red clover plants, the level of orobanchol exudation appeared to be regulated by P availability and was in good agreement with germination stimulation activity of the root exudates. This implies that under P deficiency, plant roots attract not only symbiotic fungi but also root parasitic plants through the release of strigolactones. This is the first report demonstrating that nutrient availability influences both symbiotic and parasitic interactions in the rhizosphere.

  7. HD172481 a super lithium-rich metal-deficient post-AGB binary with a red AGB companion

    CERN Document Server

    Reyniers, M; Reyniers, Maarten; Winckel, Hans Van

    2000-01-01

    We present in this paper a study on the peculiar supergiant HD172481. Its spectral type (F2Ia), high galactic latitude (b=-10.37), circumstellar dust, high radial velocity and moderate metal deficiency ([Fe/H]=-0.55) confirm the post-AGB character of this object. A detailed chemical analysis shows slight but real s-process overabundances, however no CNO-enhancement was detected. Furthermore, the spectral energy distribution and the TiO bands in the red part of the spectrum reveal a red luminous companion. The luminosity ratio of the hot F type component and this cool M type companion L(F)/L(M) is derived for a reddening of E(B-V)=0.44 (L(F)/L(M)=1.8) and indicates that the companion must also be strongly evolved and probably evolving along the AGB. Neither our photometric data-set, nor our radial velocity monitoring show evidence for orbital variability which may indicate that the period is too large for direct binary interaction. Most interestingly, a strong lithium resonance line is detected, which yields a...

  8. Far-red light-insensitive, phytochrome A-deficient mutants of tomato.

    Science.gov (United States)

    van Tuinen, A; Kerckhoffs, L H; Nagatani, A; Kendrick, R E; Koornneef, M

    1995-01-20

    We have selected two recessive mutants of tomato with slightly longer hypocotyls than the wild type, one under low fluence rate (3 mumol/m2/s) red light (R) and the other under low fluence rate blue light. These two mutants were shown to be allelic and further analysis revealed that hypocotyl growth was totally insensitive to far-red light (FR). We propose the gene symbol fri (far-red light insensitive) for this locus and have mapped it on chromosome 10. Immunochemically detectable phytochrome A polypeptide is essentially absent in the fri mutants as is the bulk spectrophotometrically detectable labile phytochrome pool in etiolated seedlings. A phytochrome B-like polypeptide is present in normal amounts and a small stable phytochrome pool can be readily detected by spectrophotometry in the fri mutants. Inhibition of hypocotyl growth by a R pulse given every 4 h is quantitatively similar in the fri mutants and wild type and the effect is to a large extent reversible if R pulses are followed immediately by a FR pulse. After 7 days in darkness, both fri mutants and the wild type become green on transfer to white light, but after 7 days in FR, the wild-type seedlings that have expanded their cotyledons lose their capacity to green in white light, while the fri mutants de-etiolate. Adult plants of the fri mutants show retarded growth and are prone to wilting, but exhibit a normal elongation response to FR given at the end of the daily photoperiod. The inhibition of seed germination by continuous FR exhibited by the wild type is normal in the fri mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Effect of reconstructive vascular surgery on red cell deformability--preliminary results.

    OpenAIRE

    Irwin, S. T.; Rocks, M J; McGuigan, J. A.; Patterson, C C; Morris, T. C.; O'Reilly, M J

    1983-01-01

    Using a simple filtration method, red cell deformability was measured in healthy control subjects and in patients with peripheral vascular disease. Impaired red cell deformability was demonstrated in patients with rest pain or gangrene and in patients with intermittent claudication. An improvement in red cell deformability was demonstrated after successful reconstructive vascular surgery in both patient groups. An improvement in red cell deformability was demonstrated in patients undergoing m...

  10. Alterations of proteins in MDCK cells during acute potassium deficiency.

    Science.gov (United States)

    Peerapen, Paleerath; Ausakunpipat, Nardtaya; Chanchaem, Prangwalai; Thongboonkerd, Visith

    2016-06-01

    Chronic K(+) deficiency can cause hypokalemic nephropathy associated with metabolic alkalosis, polyuria, tubular dilatation, and tubulointerstitial injury. However, effects of acute K(+) deficiency on the kidney remained unclear. This study aimed to explore such effects by evaluating changes in levels of proteins in renal tubular cells during acute K(+) deficiency. MDCK cells were cultivated in normal K(+) (NK) (K(+)=5.3 mM), low K(+) (LK) (K(+)=2.5 mM), or K(+) depleted (KD) (K(+)=0 mM) medium for 24 h and then harvested. Cellular proteins were resolved by two-dimensional gel electrophoresis (2-DE) and visualized by SYPRO Ruby staining (5 gels per group). Spot matching and quantitative intensity analysis revealed a total 48 protein spots that had significantly differential levels among the three groups. Among these, 46 and 30 protein spots had differential levels in KD group compared to NK and LK groups, respectively. Comparison between LK and NK groups revealed only 10 protein spots that were differentially expressed. All of these differentially expressed proteins were successfully identified by Q-TOF MS and/or MS/MS analyses. The altered levels of heat shock protein 90 (HSP90), ezrin, lamin A/C, tubulin, chaperonin-containing TCP1 (CCT1), and calpain 1 were confirmed by Western blot analysis. Global protein network analysis showed three main functional networks, including 1) cell growth and proliferation, 2) cell morphology, cellular assembly and organization, and 3) protein folding in which the altered proteins were involved. Further investigations on these networks may lead to better understanding of pathogenic mechanisms of low K(+)-induced renal injury.

  11. Multiscale Modeling of Red Blood Cells Squeezing through Submicron Slits

    Science.gov (United States)

    Peng, Zhangli; Lu, Huijie

    2016-11-01

    A multiscale model is applied to study the dynamics of healthy red blood cells (RBCs), RBCs in hereditary spherocytosis, and sickle cell disease squeezing through submicron slits. This study is motivated by the mechanical filtration of RBCs by inter-endothelial slits in the spleen. First, the model is validated by comparing the simulation results with experiments. Secondly, the deformation of the cytoskeleton in healthy RBCs is investigated. Thirdly, the mechanisms of damage in hereditary spherocytosis are investigated. Finally, the effects of cytoplasm and membrane viscosities, especially in sickle cell disease, are examined. The simulations results provided guidance for future experiments to explore the dynamics of RBCs under extreme deformation.

  12. Red blood cell aquaporin-1 expression is decreased in hereditary spherocytosis.

    Science.gov (United States)

    Crisp, Renée L; Maltaneri, Romina E; Vittori, Daniela C; Solari, Liliana; Gammella, Daniel; Schvartzman, Gabriel; García, Eliana; Rapetti, María C; Donato, Hugo; Nesse, Alcira

    2016-10-01

    Aquaporin-1 (AQP1) is the membrane water channel responsible for changes in erythrocyte volume in response to the tonicity of the medium. As the aberrant distribution of proteins in hereditary spherocytosis (HS) generates deficiencies of proteins other than those codified by the mutated gene, we postulated that AQP1 expression might be impaired in spherocytes. AQP1 expression was evaluated through flow cytometry in 5 normal controls, 1 autoimmune hemolytic anemia, 10 HS (2 mild, 3 moderate, 2 severe, and 3 splenectomized), and 3 silent carriers. The effect of AQP1 inhibitors was evaluated through water flow-based tests: osmotic fragility and hypertonic cryohemolysis. Serum osmolality was measured in 20 normal controls and 13 HS. The effect of erythropoietin (Epo) on AQP1 expression was determined in cultures of erythroleukemia UT-7 cells, dependent on Epo to survive. Independent of erythrocyte size, HS patients showed a lower content of AQP1 in erythrocyte membranes which correlated with the severity of the disease. Accordingly, red blood cells from HS subjects were less sensitive to cryohemolysis than normal erythrocytes after inhibition of the AQP1 water channel. A lower serum osmolality in HS with respect to normal controls suggests alterations during reticulocyte remodeling. The decreased AQP1 expression could contribute to explain variable degrees of anemia in hereditary spherocytosis. The finding of AQP1 expression induced by Epo in a model of erythroid cells may be interpreted as a mechanism to restore the balance of red cell water fluxes.

  13. Photodynamic treatment of red blood cell concentrates for virus inactivation enhances red blood cell aggregation: protection with antioxidants.

    Science.gov (United States)

    Ben-Hur, E; Barshtein, G; Chen, S; Yedgar, S

    1997-10-01

    Photodynamic treatment (PDT) using phthalocyanines and red light appears to be a promising procedure for decontamination of red blood cell (RBC) concentrates for transfusion. A possible complication of this treatment may be induced aggregation of RBC. The production of RBC aggregates was measured with a novel computerized cell flow properties analyzer (CFA). The PDT of RBC concentrates with sulfonated aluminum phthalocyanine (AIPcS4) and the silicon phthalocyanine Pc 4 under virucidal conditions markedly enhanced RBC aggregation and higher shear stress was required to disperse these aggregates. The clusters of cells were huge and abnormally shaped, unlike the rouleaux formed by untreated RBC. This aggregation was prevented when a mixture of antioxidants was included during PDT. Addition of the antioxidants after PDT reduced aggregation only partially. It is concluded that inclusion of antioxidants during PDT of RBC concentrates prior to transfusion may reduce or eliminate the hemodynamic risk that the virucidal treatment may present to the recipient.

  14. Unchanged binding of /sup 99/Molybdenum to red cell membrane proteins in hereditary spherocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Marik, T.; Kselikova, M.; Bibr, B.; Brabec, V.; Lener, J. (Ceskoslovenska Akademie Ved, Prague. Ustav Nuklearni Biologie a Radiochemie; Institut Hygieny a Epidemiologie, Prague (Czechoslovakia))

    1983-01-01

    The interaction of /sup 99/Mo with red cell membrane proteins was found specific for spectrin both in normal red cells and those of hereditary spherocytosis. In addition, no significant quantitative differences were observed in labelling patterns between these two types of red cells, thus indicating no major alterations in the spectrin molecules of hereditary spherocytosis.

  15. Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study.

    NARCIS (Netherlands)

    Evers, D.; Middelburg, R.A.; Haas, M. de; Zalpuri, S.; Vooght, K.M. De; Kerkhof, D. van de; Visser, O; Pequeriaux, N.C.V.; Hudig, F.; Schonewille, H.; Zwaginga, J.J.; Bom, J.G. Van Der

    2016-01-01

    BACKGROUND: Matching donor red blood cells based on recipient antigens prevents alloimmunisation. Knowledge about the immunogenicity of red-blood-cell antigens can help optimise risk-adapted matching strategies. We set out to assess the immunogenicity of red-blood-cell antigens. METHODS: In an incid

  16. Utilization and quality of cryopreserved red blood cells in transfusion medicine

    NARCIS (Netherlands)

    Henkelman, S.; Noorman, F.; Badloe, J. F.; Lagerberg, J. W. M.

    2015-01-01

    Cryopreserved (frozen) red blood cells have been used in transfusion medicine since the Vietnam war. The main method to freeze the red blood cells is by usage of glycerol. Although the usage of cryopreserved red blood cells was promising due to the prolonged storage time and the limited cellular det

  17. Online biomedical resources for malaria-related red cell disorders.

    Science.gov (United States)

    Piel, Frédéric B; Howes, Rosalind E; Nyangiri, Oscar A; Moyes, Catherine L; Williams, Thomas N; Weatherall, David J; Hay, Simon I

    2013-07-01

    Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed.

  18. Color contrast of red blood cells on solid substrate

    Science.gov (United States)

    Paiziev, Adkham A.

    2013-02-01

    In present study we developed the new method of colour visualization of red blood cells without using any chemical staining. The method based on physical phenomena a white light interference on thin transparent films. It is shown that in the case of thin human blood smears colour interference contrast occurs on solid polished substrates. The best contrast shows substrates with maximal refractive index (Mo, W, Si). These materials have been selected as substrate instead of ordinary microscopic slide in reflected light microscopy. It is shown that reflection of incident white light from blood cell surface and boundary cell-substrate generate two coherent lights. The second one (object signal) after passing through red blood cell gathers additional phase and after interference interaction with reference signal (light reflected from outer cell surface) enables cell image in colour. Number of blood smears of healthy persons (control) and patients who were diagnosed with cancer are presented. It is concluded that the offered method may be used as an effective diagnostic tool to detect early stage blood cells lesion by its interference painting in white light. Offered method may be used in research laboratories, hospitals, diagnostic centres, emergency medicine and other as complementary diagnostic tool to present convenient optical and electron microscopy technique.

  19. Characterization of red blood cells (RBCs) using dual Brillouin/Raman micro-spectroscopy

    Science.gov (United States)

    Meng, Zhaokai; Bustamante-Lopez, Sandra C.; Yakovlev, Vladislav V.; Meissner, Kenith E.

    2016-04-01

    Erythrocytes, or red blood cells, transport oxygen to and carbon dioxide from the body's tissues and organs. Red blood cell mechanical properties are altered in a number of diseases such as sickle cell anaemia and malaria. Additionally, mechanically modified red blood cell ghosts are being considered as a long-term, biocompatible carrier for drug delivery and for blood analyte sensing. Brillouin spectroscopy enables viscoelastic characterization of samples at the microscale. In this report, Brillouin spectroscopy is applied to characterize the mechanical properties of red blood cells and red blood cell ghosts.

  20. In-vitro red blood cell partitioning of doxycycline

    OpenAIRE

    P.V. Deshmukh; Badgujar, P.C.; Gatne, M.M.

    2009-01-01

    Objective: In-vitro red blood cell (RBC) partitioning of doxycycline was studied to determine whether doxycycline penetrates RBC and its concentration was assayed keeping in view its high lipophilicity. Materials and Methods: Standardization of doxycycline was performed in whole blood and plasma of cattle by microbiological assay using Bacillus subtillis ATCC 6633 as indicator organizm. Actual concentration of the drug was obtained by comparing zone inhibition with standard graph and the exte...

  1. Pure Red Cell Aplasia with Adult Onset Still's Disease

    OpenAIRE

    Nicholas Robillard; Paul Nguyen; Robert Wistaff; Mikhael Laskine

    2013-01-01

    Adult Onset Still’s Disease (AOSD) is a rare inflammatory syndrome mostly seen in young adults. Known for its wide range of clinical manifestations, AOSD often presents with nonremitting systemic signs and symptoms. Many rare case associations have been described with AOSD, but only few with pure red cell aplasia (PRCA). We are presenting a fourth known case of a young female adult with AOSD and PRCA in the literature.

  2. RED BLOOD CELL ABNORMALITIES IN DECOMPENSATED CHRONIC LIVER DISEASE (DCLD

    Directory of Open Access Journals (Sweden)

    Anbazhagan

    2015-02-01

    Full Text Available BACKGROUND: Liver plays an important role in normal erythropoiesis, especially in formation and destruction of RBC’s. Chronic liver diseases are frequently associated with hematological abnormalities. Anemia of diverge etiology occurs in about 75% patients with DCLD ( 36. This can ultimately culminate in grave complications. AIM OF THE STUDY: To detect various abnormalities in Red Blood Cells and to assess the type of anemia in DCLD. METHODS: The study was conducted in 50 patients of DCLD, in Meenakshi Medical College. A detailed History, clinical examination and also Ultrasound Abdomen, GI endoscopy to establish DCLD and complete Red Blood Cell assessment was done. RESULTS AND OBSERVATION : Among the 50 patients, 40 patients (80% had anemia and only 10 pts had normal h emoglobin above 13 gms%. About 15 patients (30% had severe Anemia of less than 6 gm%. Among the 40 patients, 25 patients had normocytic normochronic anemia, 10 patients had microcytic anemia, and 4 patients had macrocytosis and only one had dimorphic anem ia. CONCLUSION : Most common Red Blood Cell abnormality in DCLD is anemia (80% and most common anemia is normochronic normocytic anemia (62.5%, while microcytic anemia and macrocytosis were common among females and Alcoholics, respectively

  3. Associations between Red Cell Polymorphisms and Plasmodium falciparum Infection in the Middle Belt of Ghana

    Science.gov (United States)

    Amoako, Nicholas; Asante, Kwaku Poku; Adjei, George; Awandare, Gordon A.; Bimi, Langbong; Owusu-Agyei, Seth

    2014-01-01

    Background Red blood cell (RBC) polymorphisms are common in malaria endemic regions and are known to protect against severe forms of the disease. Therefore, it is important to screen for these polymorphisms in drugs or vaccines efficacy trials. This study was undertaken to evaluate associations between clinical malaria and RBC polymorphisms to assess biological interactions that may be necessary for consideration when designing clinical trials. Method In a cross-sectional study of 341 febrile children less than five years of age, associations between clinical malaria and common RBC polymorphisms including the sickle cell gene and G6PD deficiency was evaluated between November 2008 and June 2009 in the middle belt of Ghana, Kintampo. G6PD deficiency was determined by quantitative methods whiles haemoglobin variants were determined by haemoglobin titan gel electrophoresis. Blood smears were stained with Giemsa and parasite densities were determined microscopically. Results The prevalence of clinical malarial among the enrolled children was 31.9%. The frequency of G6PD deficiency was 19.0% and that for the haemoglobin variants were 74.7%, 14.7%, 9.1%, 0.9% respectively for HbAA, HbAC, HbAS and HbSS. In Multivariate regression analysis, children with the HbAS genotype had 79% lower risk of malaria infection compared to those with the HbAA genotypes (OR = 0.21, 95% CI: 0.06–0.73, p = 0.01). HbAC genotype was not significantly associated with malaria infection relative to the HbAA genotype (OR = 0.70, 95% CI: 0.35–1.42, p = 0.33). G6PD deficient subgroup had a marginally increased risk of malaria infection compared to the G6PD normal subgroup (OR = 1.76, 95% CI: 0.98–3.16, p = 0.06). Conclusion These results confirm previous findings showing a protective effect of sickle cell trait on clinical malaria infection. However, G6PD deficiency was associated with a marginal increase in susceptibility to clinical malaria compared to children without

  4. The familial Parkinson's disease gene DJ-1 (PARK7) is expressed in red cells and plays a role in protection against oxidative damage.

    Science.gov (United States)

    Xu, Xiuling; Martin, Florent; Friedman, Jeffrey S

    2010-10-15

    The antioxidant enzyme manganese superoxide dismutase (SOD2) serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in murine hematopoietic cells affects erythroid development, resulting in anemia characterized by intra-mitochondrial iron deposition, reticulocytosis and shortened red cell life span. Gene expression profiling of normal and SOD2 deficient erythroblasts identified the Parkinson's disease locus DJ-1 (Park7) as a differentially expressed transcript. To investigate the role of DJ-1 in hematopoietic cell development and protection against oxidative stress caused by Sod2 loss, we evaluated red cell parameters, reticulocyte count, red cell turnover and reactive oxygen species production in DJ-1 knockout animals and chimeric animals lacking both SOD2 and DJ-1 in hematopoietic cells generated by fetal liver transplantation. We also investigated DJ-1 protein expression in primary murine erythroid and erythroleukemia cells (MEL). Loss of DJ-1 exacerbates the phenotype of SOD2 deficiency, increasing reticulocyte count and decreasing red cell survival. Using MEL cells, we show that DJ-1 is up-regulated at the protein level during erythroid differentiation. These results indicate that DJ-1 plays a physiologic role in protection of erythroid cells from oxidant damage, a function unmasked in the context of oxidative stress.

  5. Hemoglobin Aggregation in Single Red Blood Cells of Sickle Cell Anemia

    Science.gov (United States)

    Nishio, Izumi; Tanaka, Toyoichi; Sun, Shao-Tang; Imanishi, Yuri; Tsuyoshi Ohnishi, S.

    1983-06-01

    A laser light scattering technique was used to observe the extent of hemoglobin aggregation in solitary red blood cells of sickle cell anemia. Hemoglobin aggregation was confirmed in deoxygenated cells. The light scattering technique can also be applied to cytoplasmic studies of any biological cell.

  6. Training the next generation analyst using red cell analytics

    Science.gov (United States)

    Graham, Meghan N.; Graham, Jacob L.

    2016-05-01

    We have seen significant change in the study and practice of human reasoning in recent years from both a theoretical and methodological perspective. Ubiquitous communication coupled with advances in computing and a plethora of analytic support tools have created a push for instantaneous reporting and analysis. This notion is particularly prevalent in law enforcement, emergency services and the intelligence community (IC), where commanders (and their civilian leadership) expect not only a birds' eye view of operations as they occur, but a play-by-play analysis of operational effectiveness. This paper explores the use of Red Cell Analytics (RCA) as pedagogy to train the next-gen analyst. A group of Penn State students in the College of Information Sciences and Technology at the University Park campus of The Pennsylvania State University have been practicing Red Team Analysis since 2008. RCA draws heavily from the military application of the same concept, except student RCA problems are typically on non-military in nature. RCA students utilize a suite of analytic tools and methods to explore and develop red-cell tactics, techniques and procedures (TTPs), and apply their tradecraft across a broad threat spectrum, from student-life issues to threats to national security. The strength of RCA is not always realized by the solution but by the exploration of the analytic pathway. This paper describes the concept and use of red cell analytics to teach and promote the use of structured analytic techniques, analytic writing and critical thinking in the area of security and risk and intelligence training.

  7. Dealcoholated red wine induces autophagic and apoptotic cell death in an osteosarcoma cell line.

    Science.gov (United States)

    Tedesco, I; Russo, M; Bilotto, S; Spagnuolo, C; Scognamiglio, A; Palumbo, R; Nappo, A; Iacomino, G; Moio, L; Russo, G L

    2013-10-01

    Until recently, the supposed preventive effects of red wine against cardiovascular diseases, the so-called "French Paradox", has been associated to its antioxidant properties. The interest in the anticancer capacity of polyphenols present in red wine strongly increased consequently to the enormous number of studies on resveratrol. In this study, using lyophilized red wine, we present evidence that its anticancer effect in a cellular model is mediated by apoptotic and autophagic cell death. Using a human osteosarcoma cell line, U2Os, we found that the lyophilized red wine was cytotoxic in a dose-dependent manner with a maximum effect in the range of 100-200 μg/ml equivalents of gallic acid. A mixed phenotype of types I/II cell death was evidenced by means of specific assays following treatment of U2Os with lyophilized red wine, e.g., autophagy and apoptosis. We found that cell death induced by lyophilized red wine proceeded through a mechanism independent from its anti-oxidant activity and involving the inhibition of PI3K/Akt kinase signaling. Considering the relative low concentration of each single bioactive compound in lyophilized red wine, our study suggests the activation of synergistic mechanism able to inhibit growth in malignant cells.

  8. Calcium Forms,Subcelluar Distribution and Ultrastructure of Pulp Cells as Influenced by Calcium Deficiency in Apple (Malus pumila) Fruits

    Institute of Scientific and Technical Information of China (English)

    CHEN Jian-hui; ZHOU Wei

    2004-01-01

    Calcium in Red Fuji and Starkrimson apples during storage were fractionated by sequent extracting. Localization and distribution of calcium and influence of calcium nutrition on cell ultrastructure were observed by transmission electron microscopy combined with in situ precipitation of calcium with an improved method of potassium pyroantimonate technique. Results indicated that spraying calcium solution on surface of young fruits increased contents of calcium in all forms. During storage, contents of soluble calcium and pectic calcium declined and thosein calcium phosphate, calcium oxalate and calcium silicate increased. Calcium contents of Red Fuji in all forms were higher than those of Starkrimson, indicating that calcium accumulating capability of Red Fuji fruits preceded that of Starkrimson. Under transmission electron microscopy, calcium antimonite precipitates (CaAP) was mainly distributed in cell wall, tonoplast, nuclear membrane and nucleoplasm,much more CaAP deposited in vacuole. Calcium deficiency during storage leads to decrease of CaAP in locations mentioned above, disappearance of compartmentation, and entrance of CaAP to cytoplasm. Transformation from soluble calcium and pectic calcium to calcium phosphate,oxalate and damages of biomembranes structuraly and functionally resulted from calcium deficiency during storage were the crucial causation of physiological disorder.

  9. Flow of Red Blood Cells in Stenosed Microvessels

    Science.gov (United States)

    Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

    2016-06-01

    A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis.

  10. Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells.

    Science.gov (United States)

    de Wolski, Karen; Fu, Xiaoyoun; Dumont, Larry J; Roback, John D; Waterman, Hayley; Odem-Davis, Katherine; Howie, Heather L; Zimring, James C

    2016-05-01

    Transfusion of red blood cells is a very common inpatient procedure, with more than 1 in 70 people in the USA receiving a red blood cell transfusion annually. However, stored red blood cells are a non-uniform product, based upon donor-to-donor variation in red blood cell storage biology. While thousands of biological parameters change in red blood cells over storage, it has remained unclear which changes correlate with function of the red blood cells, as opposed to being co-incidental changes. In the current report, a murine model of red blood cell storage/transfusion is applied across 13 genetically distinct mouse strains and combined with high resolution metabolomics to identify metabolic changes that correlated with red blood cell circulation post storage. Oxidation in general, and peroxidation of lipids in particular, emerged as changes that correlated with extreme statistical significance, including generation of dicarboxylic acids and monohydroxy fatty acids. In addition, differences in anti-oxidant pathways known to regulate oxidative stress on lipid membranes were identified. Finally, metabolites were identified that differed at the time the blood was harvested, and predict how the red blood cells perform after storage, allowing the potential to screen donors at time of collection. Together, these findings map out a new landscape in understanding metabolic changes during red blood cell storage as they relate to red blood cell circulation.

  11. Ectopic lignification in primary cellulose-deficient cell walls of maize cell suspension cultures

    Institute of Scientific and Technical Information of China (English)

    Hugo Melida; Antonio Encina; Asier Largo-Gosens; Esther Novo-Uzal; Rogelio Santiago; Federico Pomar; Pedro Garca; Penelope Garca-Angulo; Jose Luis Acebes; Jesus Alvarez

    2015-01-01

    Maize (Zea mays L.) suspension-cultured cells with up to 70% less cellulose were obtained by stepwise habituation to dichlobenil (DCB), a cellulose biosynthesis inhibitor. Cellulose deficiency was accompanied by marked changes in cell wall matrix polysaccharides and phenolics as revealed by Fourier transform infrared (FTIR) spectroscopy. Cell wall compositional analysis indicated that the cellulose-deficient cell walls showed an enhancement of highly branched and cross-linked arabinoxylans, as well as an increased content in ferulic acid, diferulates and p-coumaric acid, and the presence of a polymer that stained positive for phloroglucinol. In accordance with this, cellulose-deficient cell walls showed a fivefold increase in Klason-type lignin. Thioacidolysis/GC-MS analysis of cellulose-deficient cell walls indicated the presence of a lignin-like polymer with a Syringyl/Guaiacyl ratio of 1.45, which differed from the sensu stricto stress-related lignin that arose in response to short-term DCB-treatments. Gene expression analysis of these cells indicated an overexpression of genes specific for the biosynthesis of monolignol units of lignin. A study of stress signaling pathways revealed an overexpression of some of the jasmonate signaling pathway genes, which might trigger ectopic lignification in response to cell wall integrity disruptions. In summary, the structural plasticity of primary cell walls is proven, since a lignification process is possible in response to cellulose impoverishment.

  12. Trapping red blood cells in living animals using optical tweezers.

    Science.gov (United States)

    Zhong, Min-Cheng; Wei, Xun-Bin; Zhou, Jin-Hua; Wang, Zi-Qiang; Li, Yin-Mei

    2013-01-01

    The recent development of non-invasive imaging techniques has enabled the visualization of molecular events underlying cellular processes in live cells. Although microscopic objects can be readily manipulated at the cellular level, additional physiological insight is likely to be gained by manipulation of cells in vivo, which has not been achieved so far. Here we use infrared optical tweezers to trap and manipulate red blood cells within subdermal capillaries in living mice. We realize a non-contact micro-operation that results in the clearing of a blocked microvessel. Furthermore, we estimate the optical trap stiffness in the capillary. Our work expands the application of optical tweezers to the study of live cell dynamics in animals.

  13. Of macrophages and red blood cells; a complex love story.

    Directory of Open Access Journals (Sweden)

    Djuna Zoe de Back

    2014-01-01

    Full Text Available Macrophages tightly control the production and clearance of red blood cells (RBC. During steady state haematopoiesis, approximately 1010 red blood cells are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages.

  14. Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

    Science.gov (United States)

    Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

    2017-01-01

    Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

  15. Evaluation of Red Cell Membrane Cytoskeletal Disorders Using a Flow Cytometric Method in South Iran

    Directory of Open Access Journals (Sweden)

    Habib Alah Golafshan

    2014-03-01

    Full Text Available OBJECTIVE: The diagnosis of hereditary red blood cell (RBC membrane disorders, and in particular hereditary spherocytosis (HS and Southeast Asian ovalocytosis (SAO, is based on clinical history, RBC morphology, and other conventional tests such as osmotic fragility. However, there are some milder cases of these disorders that are difficult to diagnose. The application of eosin-5’-maleimide (EMA was evaluated for screening of RBC membrane defects along with some other anemias. We used EMA dye, which binds mostly to band 3 protein and to a lesser extent some other membrane proteins, for screening of some membrane defects such as HS. METHODS: Fresh RBCs from hematologically normal controls and patients with HS, SAO, hereditary elliptocytosis, hereditary spherocytosis with pincered cells, severe iron deficiency, thalassemia minor, and autoimmune hemolytic anemia were stained with EMA dye and analyzed for mean fluorescent intensity (MFI using a flow cytometer. RESULTS: RBCs from patients with HS and iron deficiency showed a significant reduction in MFI compared to those from normal controls (p<0.0001 and p<0.001, respectively, while macrocytic RBCs showed a significant increase in MFI (p<0.01. A significant correlation was shown between mean corpuscular volume and MFI, with the exceptions of HS and thalassemia minor. CONCLUSION: Our results showed that the flow cytometric method could be a reliable diagnostic method for screening and confirmation, with higher sensitivity and specificity (95% and 93%, respectively than conventional routine tests for HS patients prior to further specific membrane protein molecular tests.

  16. Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells.

    Science.gov (United States)

    Daud, Hasbullah; Browne, Susan; Al-Majmaie, Rasoul; Murphy, William; Al-Rubeai, Mohamed

    2016-01-25

    An understanding of the metabolic profile of cell proliferation and differentiation should support the optimization of culture conditions for hematopoietic stem and progenitor cell (HSPC) proliferation, differentiation, and maturation into red blood cells. We have evaluated the key metabolic parameters during each phase of HSPC culture for red blood cell production in serum-supplemented (SS) and serum-free (SF) conditions. A simultaneous decrease in growth rate, total protein content, cell size, and the percentage of cells in the S/G2 phase of cell cycle, as well as an increase in the percentage of cells with a CD71(-)/GpA(+) surface marker profile, indicates HSPC differentiation into red blood cells. Compared with proliferating HSPCs, differentiating HSPCs showed significantly lower glucose and glutamine consumption rates, lactate and ammonia production rates, and amino acid consumption and production rates in both SS and SF conditions. Furthermore, extracellular acidification was associated with late proliferation phase, suggesting a reduced cellular metabolic rate during the transition from proliferation to differentiation. Under both SS and SF conditions, cells demonstrated a high metabolic rate with a mixed metabolism of both glycolysis and oxidative phosphorylation (OXPHOS) in early and late proliferation, an increased dependence on OXPHOS activity during differentiation, and a shift to glycolytic metabolism only during maturation phase. These changes indicate that cell metabolism may have an important impact on the ability of HSPCs to proliferate and differentiate into red blood cells.

  17. Pathogen Inactivation of red cells: challenges and opportunities

    Institute of Scientific and Technical Information of China (English)

    Stephen J. Wagner

    2006-01-01

    @@ Introduction Virus inactivation methods for blood have been explored as a means to further reduce the risk from tested agents and to decrease the risk of emerging or variant agents for whom no deferral or effective screening methods are available. Although inactivation methods promise to reduce transfusion-related infectious disease risk, these methods are not perfect. Most techniques for pathogen reduction will not kill bacterial spores, or inactivate bacterial endotoxin, prion protein, or certain non-enveloped viruses whose tightly packed capsid proteins prevent access of the virucidal agent to its nucleic acid target. In addition,various inactivation methods have been known to decrease blood cell yield, affect blood cell recovery or survival, and may pose risk to recipients or blood center workers. My presentation today will review two methods for pathogen inactivation of red cells.

  18. Manipulation on human red blood cells with femtosecond optical tweezers

    Institute of Scientific and Technical Information of China (English)

    Ming Zhou; Haifeng Yang; Jianke Di; Enlan Zhao

    2008-01-01

    Different types of femtosecond optical tweezers have become a powerful tool in the modern biological field. However, how to control the irregular targets, including biological cells, using femtosecond optical tweezers remains to be explored. In this study, human red blood cells (hRBCs) are manipulated with femtosecond optical tweezers, and their states under different laser powers are investigated. The results indicate that optical potential traps only can capture the edge of hRBCs under the laser power from 1.4 to 2.8 mW, while it can make hRBCs turn over with the laser power more than 2.8 roW. It is suggested that femtosecond optical tweezers could not only manipulate biological cells, but also subtly control its states by adjusting the laser power.

  19. Copper(II) complexes encapsulated in human red blood cells.

    Science.gov (United States)

    Bonomo, R P; De Flora, A; Rizzarelli, E; Santoro, A M; Tabbí, G; Tonetti, M

    1995-09-01

    Copper(II) complexes were encapsulated in human red blood cells in order to test their possible use as antioxidant drugs by virtue of their labile character. ESR spectroscopy was used to verify whether encapsulation in red blood cells leads to the modification of such complexes. With copper(II) complexes bound to dipeptides or tripeptides, an interaction with hemoglobin was found to be present, the hemoglobin having a strong coordinative site formed by four nitrogen donor atoms. Instead, with copper(II) complexes with TAD or PheANN3, which have the greatest stability. ESR spectra always showed the original species. Only the copper(II) complex with GHL gave rise to a complicated behavior, which contained signals from iron(III) species probably coming from oxidative processes. Encapsulation of all copper(II) complexes in erythrocytes caused a slight oxidative stress, compared to the unloaded and to the native cells. However, no significant differences were observed in the major metabolic properties (GSH, glycolytic rate, hexose monophosphate shunt, Ca(2+)-ATPase) of erythrocytes loaded with different copper(II) complexes, with the exception of methemoglobin levels, which were markedly increased in the case of [Cu(GHL)H-1] compared to [Cu(TAD)]. This latter finding suggests that methemoglobin formation can be affected by the type of complex used for encapsulation, depending on the direct interaction of the copper(II) complex with hemoglobin.

  20. Structural analysis of red blood cell aggregates under shear flow.

    Science.gov (United States)

    Chesnutt, J K W; Marshall, J S

    2010-03-01

    A set of measures of red blood cell (RBC) aggregates are developed and applied to examine the aggregate structure under plane shear and channel flows. Some of these measures are based on averages over the set of red blood cells which are in contact with each other at a given time. Other measures are developed by first fitting an ellipse to the planar projection of the aggregate, and then examining the area and aspect ratio of the fit ellipse as well as the orientations of constituent RBCs with respect to the fit ellipse axes. The aggregate structural measures are illustrated using a new mesoscale computational model for blood cell transport, collision and adhesion. The sensitivity of this model to change in adhesive surface energy density and shear rate on the aggregate structure is examined. It is found that the mesoscale model predictions exhibit reasonable agreement with experimental and theoretical data for blood flow in plane shear and channel flows. The new structural measures are used to examine the differences between predictions of two- and three-dimensional computations of the aggregate formation, showing that two-dimensional computations retain some of the important aspects of three-dimensional computations.

  1. Diagnosis and epidemiology of red blood cell enzyme disorders

    Directory of Open Access Journals (Sweden)

    Richard Van Wijk

    2013-03-01

    Full Text Available The red blood cell possess an active metabolic machinery that provides the cell with energy to pump ions against electrochemical gradients, to maintain its shape, to keep hemoglobin iron in the reduced (ferrous form, and to maintain enzyme and hemoglobin sulfhydryl groups. The main source of metabolic energy comes from glucose. Glucose is metabolized through the glycolytic pathway and through the hexose monophosphate shunt. Glycolysis catabolizes glucose to pyruvate and lactate, which represent the end products of glucose metabolism in the erythrocyte. Adenosine diphosphate (ADP is phosphorylated to adenosine triphosphate (ATP, and nicotinamide adenine dinucleotide (NAD+ is reduced to NADH in glycolysis. 2,3- Bisphosphoglycerate, an important regulator of the oxygen affinity of hemoglobin, is generated during glycolysis by the Rapoport-Luebering shunt. The hexose monophosphate shunt oxidizes glucose-6-phosphate, reducing NADP+ to reduced nicotinamide adenine dinucleotide phosphate (NADPH. The red cell lacks the capacity for de novo purine synthesis but has a salvage pathway that permits synthesis of purine nucleotides from purine bases...

  2. The nature of multiphoton fluorescence from red blood cells

    Science.gov (United States)

    Saytashev, Ilyas; Murphy, Michael; Osseiran, Sam; Spence, Dana M.; Evans, Conor L.; Dantus, Marcos

    2016-03-01

    We report on the nature of multiphoton excited fluorescence observed from human erythrocytes (red blood cells RBC's) and their "ghosts" following 800nm sub-15 fs excitation. The detected optical signal is assigned as two-photon excited fluorescence from hemoglobin. Our findings are supported by wavelength-resolved fluorescence lifetime decay measurements using time-correlated single photon counting system from RBC's, their ghosts as well as in vitro samples of various fluorophores including riboflavin, NADH, NAD(P)H, hemoglobin. We find that low-energy and short-duration pulses allow two-photon imaging of RBC's, but longer more intense pulses lead to their destruction.

  3. General coarse-grained red blood cell models: I. Mechanics

    OpenAIRE

    FEDOSOV, DMITRY A.; Caswell, Bruce; Karniadakis, George E.

    2009-01-01

    We present a rigorous procedure to derive coarse-grained red blood cell (RBC) models, which lead to accurate mechanical properties of realistic RBCs. Based on a semi-analytic theory linear and non-linear elastic properties of the RBC membrane can be matched with those obtained in optical tweezers stretching experiments. In addition, we develop a nearly stress-free model which avoids a number of pitfalls of existing RBC models, such as non-biconcave equilibrium shape and dependence of RBC mech...

  4. Swinging of red blood cells under shear flow

    CERN Document Server

    Abkarian, M; Viallat, A; Abkarian, Manouk; Faivre, Magalie; Viallat, Annie

    2007-01-01

    We reveal that under moderate shear stress (of the order of 0.1 Pa) red blood cells present an oscillation of their inclination (swinging) superimposed to the long-observed steady tanktreading (TT) motion. A model based on a fluid ellipsoid surrounded by a visco-elastic membrane initially unstrained (shape memory) predicts all observed features of the motion: an increase of both swinging amplitude and period (1/2 the TT period) upon decreasing the shear stress, a shear stress-triggered transition towards a narrow shear stress-range intermittent regime of successive swinging and tumbling, and a pure tumbling motion at lower shear stress-values.

  5. Bacterial glycosidases for the production of universal red blood cells

    DEFF Research Database (Denmark)

    Liu, Qiyong P; Sulzenbacher, Gerlind; Yuan, Huaiping;

    2007-01-01

    Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating...... of the alpha-N-acetylgalactosaminidase family reveals an unusual catalytic mechanism involving NAD+. The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions....

  6. Manipulation of microparticles and red blood cells using optoelectronic tweezers

    Indian Academy of Sciences (India)

    R S Verma; R Dasgupta; N Kumar; S Ahlawat; A Uppal; P K Gupta

    2014-02-01

    We report the development of an optoelectronic tweezers set-up which works by lightinduced dielectrophoresis mechanism to manipulate microparticles. We used thermal evaporation technique for coating the organic polymer, titanium oxide phthalocyanine (TiOPc), as a photoconductive layer on ITO-coated glass slide. Compare to the conventional optical tweezers, the technique requires optical power in W range and provides a manipulation area of a few mm2. The set-up was used to manipulate the polystyrene microspheres and red blood cells (RBCs). The RBCs could be attracted or repelled by varying the frequency of the applied AC bias.

  7. THE PURE RED BLOOD CELL APLASIA IN RENAL TRANSPLANT RECIPIENT

    Directory of Open Access Journals (Sweden)

    B. T. Dzumabaeva

    2011-01-01

    Full Text Available The pure red blood cell aplasia of renal transplant recipients caused by parvovirus B19 (PB19 is characterized by persistent anemia which resistant to erythropoietin therapy, lack of reticulocytes, bone marrow hypoplasia, and clinically accompanied by severe recurrent bacterial, fungal and viral infection. In case of reactivation PB19 it is necessarv, first of all, eliminate the causes activation of this virus and to cancel or reduce the dose of drugs which depressed the normal hematopoiesis germs, thus to reduce the pancytopenia associating complications in this population. 

  8. [Red Blood Cells Raman Spectroscopy Comparison of Type Two Diabetes Patients and Rats].

    Science.gov (United States)

    Wang, Lei; Liu, Gui-dong; Mu, Xin; Xiao, Hong-bin; Qi, Chao; Zhang, Si-qi; Niu Wen-ying; Jiang, Guang-kun; Feng, Yue-nan; Bian, Jing-qi

    2015-10-01

    By using confocal Raman spectroscopy, Raman spectra were measured in normal rat red blood cells, normal human red blood cells, STZ induced diabetetic rats red blood cells, Alloxan induced diabetetic rats red blood cells and human type 2 diabetes red blood cells. Then principal component analysis (PCA) with support vector machine (SVM) classifier was used for data analysis, and then the distance between classes was used to judge the degree of close to two kinds of rat model with type 2 diabetes. The results found significant differences in the Raman spectra of red blood cell in diabetic and normal red blood cells. To diabetic red blood cells, the peak in the amide VI C=O deformation vibration band is obvious, and amide V N-H deformation vibration band spectral lines appear deviation. Belong to phospholipid fatty acyl C-C skeleton, the 1 130 cm(-1) spectral line is enhanced and the 1 088 cm(-1) spectral line is abated, which show diabetes red cell membrane permeability increased. Raman spectra of PCA combined with SVM can well separate 5 types of red blood cells. Classifier test results show that the classification accuracy is up to 100%. Through the class distance between the two induced method and human type 2 diabetes, it is found that STZ induced model is more close to human type 2 diabetes. In conclusion, Raman spectroscopy can be used for diagnosis of diabetes and rats STZ induced diabetes method is closer to human type 2 diabetes.

  9. Cobalt uptake and binding in human red blood cells.

    Science.gov (United States)

    Simonsen, Lars Ole; Brown, Anthony M; Harbak, Henrik; Kristensen, Berit I; Bennekou, Poul

    2011-04-15

    The basal uptake and cytoplasmic binding of cobalt was studied in human red cells using (57)Co as tracer. The basal uptake is linear with time, at a rate of about 10 μmol (l cells)(-1) h(-1) at 100 μM [Co(2+)](o), and is almost irreversible, as there is hardly any efflux into excess EDTA. Ionophore A23187 mediates a rapid equilibration of Co(2+) across the cell membrane leading to a marked accumulation, reflecting effective cytoplasmic buffering. The fraction (α(Co)) of total cell cobalt being present as free, ionized Co(2+) is estimated at α(Co)=0.01 from the equilibrium distribution of cobalt, and also from the initial slope of the cobalt buffering curve. The cobalt accumulation is similar in fed and ATP-depleted cells. The buffering curve for [Co(T)](c) can be fitted by a Michaelis type function with B(max)=24 mmol (l cells)(-1) and half-saturation at 240 μM [Co(2+)](c). The tracer influx curves are adequately fitted by single exponentials, whereas the net influx curves all require at least double exponential fits, probably due to non-stationary A23187 kinetics. The rate of tracer influx decreases with increasing cobalt concentration, and increases with delayed addition of (57)Co tracer during net uptake. This might be explained by an 'auto-inhibition' by cobalt. The kinetics for A23187-mediated net and tracer influx of (54)Mn is very similar to that of (57)Co, whereas the net influx of (65)Zn can be fitted by single exponentials. In cobalt-loaded cells the cobalt is partly reversibly bound, being releasable by excess extracellular EGTA in the presence of A23187, and partly tightly bound, remaining in the cells even at high ionophore concentrations. The tightly bound fraction builds up over time, and is larger and develops earlier in fed cells compared to ATP-depleted cells. However, all cell cobalt appears to exchange with (57)Co during tracer influx. It is speculated that oxidation of Co(2+) to Co(3+) could lead to the high affinity binding. Tight binding

  10. Phenotypic studies of natural killer cell subsets in human transporter associated with antigen processing deficiency.

    Directory of Open Access Journals (Sweden)

    Jacques Zimmer

    Full Text Available Peripheral blood natural killer (NK cells from patients with transporter associated with antigen processing (TAP deficiency are hyporesponsive. The mechanism of this defect is unknown, but the phenotype of TAP-deficient NK cells is almost normal. However, we noticed a high percentage of CD56(bright cells among total NK cells from two patients. We further investigated TAP-deficient NK cells in these patients and compared them to NK cells from two other TAP-deficient patients with no clinical symptoms and to individuals with chronic inflammatory diseases other than TAP deficiency (chronic lung diseases or vasculitis. Peripheral blood mononuclear cells isolated from venous blood were stained with fluorochrome-conjugated antibodies and the phenotype of NK cells was analyzed by flow cytometry. In addition, (51Chromium release assays were performed to assess the cytotoxic activity of NK cells. In the symptomatic patients, CD56(bright NK cells represented 28% and 45%, respectively, of all NK cells (higher than in healthy donors. The patients also displayed a higher percentage of CD56(dimCD16(- NK cells than controls. Interestingly, this unusual NK cell subtype distribution was not found in the two asymptomatic TAP-deficient cases, but was instead present in several of the other patients. Over-expression of the inhibitory receptor CD94/NKG2A by TAP-deficient NK cells was confirmed and extended to the inhibitory receptor ILT2 (CD85j. These inhibitory receptors were not involved in regulating the cytotoxicity of TAP-deficient NK cells. We conclude that expansion of the CD56(bright NK cell subtype in peripheral blood is not a hallmark of TAP deficiency, but can be found in other diseases as well. This might reflect a reaction of the immune system to pathologic conditions. It could be interesting to investigate the relative distribution of NK cell subsets in various respiratory and autoimmune diseases.

  11. Red Fluorescent Carbon Nanoparticle-Based Cell Imaging Probe.

    Science.gov (United States)

    Ali, Haydar; Bhunia, Susanta Kumar; Dalal, Chumki; Jana, Nikhil R

    2016-04-13

    Fluorescent carbon nanoparticle-based probes with tunable visible emission are biocompatible, environment friendly and most suitable for various biomedical applications. However, synthesis of red fluorescent carbon nanoparticles and their transformation into functional nanoparticles are very challenging. Here we report red fluorescent carbon nanoparticle-based nanobioconjugates of nanoparticles are synthesized via high temperature colloid-chemical approach and transformed into water-soluble functional nanoparticles via coating with amphiphilic polymer followed by covalent linking with desired biomolecules. Following this approach, carbon nanoparticles are functionalized with polyethylene glycol, primary amine, glucose, arginine, histidine, biotin and folic acid. These functional nanoparticles can be excited with blue/green light (i.e., 400-550 nm) to capture their emission spanning from 550 to 750 nm. Arginine and folic acid functionalized nanoparticles have been demonstrated as fluorescent cell labels where blue and green excitation has been used for imaging of labeled cells. The presented method can be extended for the development of carbon nanoparticle-based other bioimaging probes.

  12. Acetylsalicylic acid and morphology of red blood cells

    Directory of Open Access Journals (Sweden)

    Jacques Natan Grinapel Frydman

    2010-06-01

    Full Text Available This work evaluated the effect of in vitro and in vivo treatment with ASA on the morphology of the red blood cells. Blood samples or Wistar rats were treated with ASA for one hour. Blood samples or animals treated with saline were used as control group. Blood smears were prepared, fixed, stained and the qualitative and quantitative morphology of red blood cells were evaluated under optical microscopy. Data showed that the in vitro treatment for one hour with ASA at higher dose used significantly (pEste trabalho avaliou o efeito do tratamento in vitro e in vivo com AAS na morfologia dos eritrócitos. Amostras de sangue ou ratos Wistar foram tratadas com AAS por uma hora. Amostras sangüíneas ou animais tratados com salina foram utilizados como grupos controle. Distensões de sangue foram preparadas, fixadas, coradas e a análise morfológica qualitativa e quantitativa dos eritrócitos foi realizada em microscópio óptico. Os dados mostraram que o tratamento in vitro por uma hora com AAS na maior dose utilizada modificou significativamente (p<0.05 a relação perímetro/área dos eritrócitos. Não foram obtidas alterações morfológicas com o tratamento in vivo. O uso do AAS em doses altas poderia interferir na forma dos eritrócitos.

  13. Generation of glycosylphosphatidylinositol anchor protein-deficient blood cells from human induced pluripotent stem cells.

    Science.gov (United States)

    Yuan, Xuan; Braunstein, Evan M; Ye, Zhaohui; Liu, Cyndi F; Chen, Guibin; Zou, Jizhong; Cheng, Linzhao; Brodsky, Robert A

    2013-11-01

    PIG-A is an X-linked gene required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIG-A mutant cells have a deficiency or absence of all GPI-anchored proteins (GPI-APs). Acquired mutations in hematopoietic stem cells result in the disease paroxysmal nocturnal hemoglobinuria, and hypomorphic germline PIG-A mutations lead to severe developmental abnormalities, seizures, and early death. Human induced pluripotent stem cells (iPSCs) can differentiate into cell types derived from all three germ layers, providing a novel developmental system for modeling human diseases. Using PIG-A gene targeting and an inducible PIG-A expression system, we have established, for the first time, a conditional PIG-A knockout model in human iPSCs that allows for the production of GPI-AP-deficient blood cells. PIG-A-null iPSCs were unable to generate hematopoietic cells or any cells expressing the CD34 marker and were defective in generating mesodermal cells expressing KDR/VEGFR2 (kinase insert domain receptor) and CD56 markers. In addition, PIG-A-null iPSCs had a block in embryonic development prior to mesoderm differentiation that appears to be due to defective signaling through bone morphogenetic protein 4. However, early inducible PIG-A transgene expression allowed for the generation of GPI-AP-deficient blood cells. This conditional PIG-A knockout model should be a valuable tool for studying the importance of GPI-APs in hematopoiesis and human development.

  14. Geometric localization of thermal fluctuations in red blood cells.

    Science.gov (United States)

    Evans, Arthur A; Bhaduri, Basanta; Popescu, Gabriel; Levine, Alex J

    2017-02-27

    The thermal fluctuations of membranes and nanoscale shells affect their mechanical characteristics. Whereas these fluctuations are well understood for flat membranes, curved shells show anomalous behavior due to the geometric coupling between in-plane elasticity and out-of-plane bending. Using conventional shallow shell theory in combination with equilibrium statistical physics we theoretically demonstrate that thermalized shells containing regions of negative Gaussian curvature naturally develop anomalously large fluctuations. Moreover, the existence of special curves, "singular lines," leads to a breakdown of linear membrane theory. As a result, these geometric curves effectively partition the cell into regions whose fluctuations are only weakly coupled. We validate these predictions using high-resolution microscopy of human red blood cells (RBCs) as a case study. Our observations show geometry-dependent localization of thermal fluctuations consistent with our theoretical modeling, demonstrating the efficacy in combining shell theory with equilibrium statistical physics for describing the thermalized morphology of cellular membranes.

  15. Geometric localization of thermal fluctuations in red blood cells

    Science.gov (United States)

    Evans, Arthur A.; Bhaduri, Basanta; Popescu, Gabriel; Levine, Alex J.

    2017-01-01

    The thermal fluctuations of membranes and nanoscale shells affect their mechanical characteristics. Whereas these fluctuations are well understood for flat membranes, curved shells show anomalous behavior due to the geometric coupling between in-plane elasticity and out-of-plane bending. Using conventional shallow shell theory in combination with equilibrium statistical physics we theoretically demonstrate that thermalized shells containing regions of negative Gaussian curvature naturally develop anomalously large fluctuations. Moreover, the existence of special curves, “singular lines,” leads to a breakdown of linear membrane theory. As a result, these geometric curves effectively partition the cell into regions whose fluctuations are only weakly coupled. We validate these predictions using high-resolution microscopy of human red blood cells (RBCs) as a case study. Our observations show geometry-dependent localization of thermal fluctuations consistent with our theoretical modeling, demonstrating the efficacy in combining shell theory with equilibrium statistical physics for describing the thermalized morphology of cellular membranes. PMID:28242681

  16. Transfusion of Red Blood Cells to Patients with Sepsis.

    Science.gov (United States)

    Chan, Yi-Ling; Han, Shih-Tsung; Li, Chih-Huang; Wu, Chin-Chieh; Chen, Kuan-Fu

    2017-09-11

    Sepsis is one of the major causes of death worldwide, and is the host response to infection which renders our organs malfunctioning. Insufficient tissue perfusion and oxygen delivery have been implicated in the pathogenesis of sepsis-related organ dysfunction, making transfusion of packed red blood cells (pRBCs) a reasonable treatment modality. However, clinical trials have generated controversial results. Even the notion that transfused pRBCs increase the oxygen-carrying capacity of blood has been challenged. Meanwhile, during sepsis, the ability of our tissues to utilize oxygen may also be reduced, and the increased blood concentrations of lactate may be the results of strong inflammation and excessive catecholamine release, rather than impaired cell respiration. Leukodepleted pRBCs more consistently demonstrated improvement in microcirculation, and the increase in blood viscosity brought about by pRBC transfusion helps maintain functional capillary density. A restrictive strategy of pRBC transfusion is recommended in treating septic patients.

  17. From stem cell to erythroblast: regulation of red cell production at multiple levels by multiple hormones.

    Science.gov (United States)

    Lodish, Harvey; Flygare, Johan; Chou, Song

    2010-07-01

    This article reviews the regulation of production of red blood cells at several levels: (1) the ability of erythropoietin and adhesion to a fibronectin matrix to stimulate the rapid production of red cells by inducing terminal proliferation and differentiation of committed erythroid CFU-E progenitors; (2) the regulated expansion of the pool of earlier BFU-E erythroid progenitors by glucocorticoids and other factors that occurs during chronic anemia or inflammation; and (3) the expansion of thehematopoietic cell pool to produce more progenitors of all hematopoietic lineages.

  18. Thymidine kinase 1 deficient cells show increased survival rate after UV-induced DNA damage

    DEFF Research Database (Denmark)

    Skovgaard, T; Rasmussen, Lene Juel; Munch-Petersen, Birgitte

    2010-01-01

    Balanced deoxynucleotide pools are known to be important for correct DNA repair, and deficiency for some of the central enzymes in deoxynucleotide metabolism can cause imbalanced pools, which in turn can lead to mutagenesis and cell death. Here we show that cells deficient for the thymidine salvage...

  19. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

    DEFF Research Database (Denmark)

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva

    2011-01-01

    Rhoh is a hematopoietic system-specific GTPase. Rhoh-deficient T cells have been shown to have a defect in TCR signaling manifested during their thymic development. Our aims were to investigate the phenotype of peripheral Rhoh-deficient T cells and to explore in vivo the potential benefit of Rhoh...

  20. DETERMINANTS OF RED-BLOOD-CELL DEFORMABILITY IN RELATION TO CELL AGE

    NARCIS (Netherlands)

    BOSCH, FH; WERRE, JM; ROERDINKHOLDERSTOELWINDER, B; HULS, T; WILLEKENS, FLA; WICHERS, G; HALIE, MR

    1994-01-01

    Red blood cell (RBC) deformability was determined with an ektacytometer in fractions separated on the basis of differences in cell volume or density. Deformability was measured with ektacytometry (rpm-scan and osmo-scan). We studied three groups of RBC fractions:l. By counterflow centrifugation we o

  1. Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid

    Directory of Open Access Journals (Sweden)

    Hongbin Tu

    2015-11-01

    Full Text Available Strategies to prevent diabetic microvascular angiopathy focus on the vascular endothelium. Because red blood cells (RBCs are less deformable in diabetes, we explored an original concept linking decreased RBC deformability to RBC ascorbate and hyperglycemia. We characterized ascorbate concentrations from human and mouse RBCs and plasma, and showed an inverse relationship between RBC ascorbate concentrations and deformability, measured by osmotic fragility. RBCs from ascorbate deficient mice were osmotically sensitive, appeared as spherocytes, and had decreased β-spectrin. These aberrancies reversed with ascorbate repletion in vivo. Under physiologic conditions, only ascorbate's oxidation product dehydroascorbic acid (DHA, a substrate for facilitated glucose transporters, was transported into mouse and human RBCs, with immediate intracellular reduction to ascorbate. In vitro, glucose inhibited entry of physiologic concentrations of dehydroascorbic acid into mouse and human RBCs. In vivo, plasma glucose concentrations in normal and diabetic mice and humans were inversely related to respective RBC ascorbate concentrations, as was osmotic fragility. Human RBC β-spectrin declined as diabetes worsened. Taken together, hyperglycemia in diabetes produced lower RBC ascorbate with increased RBC rigidity, a candidate to drive microvascular angiopathy. Because glucose transporter expression, DHA transport, and its inhibition by glucose differed for mouse versus human RBCs, human experimentation is indicated.

  2. Defected red blood cell membranes and direct correlation with the uraemic milieu: the connection with the decreased red blood cell lifespan observed in haemodialysis patients

    Science.gov (United States)

    Stamopoulos, D.; Grapsa, E.; Manios, E.; Gogola, V.; Bakirtzi, N.

    2012-12-01

    Together with impaired production of erythropoietin and iron deficiency, the decreased lifespan of red blood cells (RBCs) is a main factor contributing to the chronic anaemia observed in haemodialysis (HD) patients. Atomic force microscopy is employed in this work to thoroughly survey the membrane of intact RBCs (iRBCs) of HD patients in comparison to those of healthy donors, aiming to obtain direct information on the structural status of RBCs that can be related to their decreased lifespan. We observed that the iRBC membrane of the HD patients is overpopulated with extended circular defects, termed ‘orifices’, that have typical dimension ranging between 0.2 and 1.0 μm. The ‘orifice’ index—that is, the mean population of ‘orifices’ per top membrane surface—exhibits a pronounced relative increase of order 54 ± 12% for the HD patients as compared to healthy donors. Interestingly, for the HD patients, the ‘orifice’ index, which relates to the structural status of the RBC membrane, correlates strongly with urea concentration, which is a basic index of the uraemic milieu. Thus, these results indicate that the uraemic milieu downgrades the structural status of the RBC membrane, possibly triggering biochemical processes that result in their premature elimination from the circulation. This process could decrease the lifespan of RBCs, as observed in HD patients.

  3. Stretching and relaxation of malaria-infected red blood cells.

    Science.gov (United States)

    Ye, Ting; Phan-Thien, Nhan; Khoo, Boo Cheong; Lim, Chwee Teck

    2013-09-03

    The invasion of red blood cells (RBCs) by malaria parasites is a complex dynamic process, in which the infected RBCs gradually lose their deformability and their ability to recover their original shape is greatly reduced with the maturation of the parasites. In this work, we developed two types of cell model, one with an included parasite, and the other without an included parasite. The former is a representation of real malaria-infected RBCs, in which the parasite is treated as a rigid body. In the latter, where the parasite is absent, the membrane modulus and viscosity are elevated so as to produce the same features present in the parasite model. In both cases, the cell membrane is modeled as a viscoelastic triangular network connected by wormlike chains. We studied the transient behaviors of stretching deformation and shape relaxation of malaria-infected RBCs based on these two models and found that both models can generate results in agreement with those of previously published studies. With the parasite maturation, the shape deformation becomes smaller and smaller due to increasing cell rigidity, whereas the shape relaxation time becomes longer and longer due to the cell's reduced ability to recover its original shape.

  4. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans

    OpenAIRE

    Warnatz, Klaus; Salzer, Ulrich; Rizzi, Marta; Fischer, Beate; Gutenberger, Sylvia; Böhm, Joachim; Kienzler, Anne-Kathrin; Pan-Hammarström, Qiang; Hammarström, Lennart; Rakhmanov, Mirzokhid; Schlesier, Michael; Grimbacher, Bodo; Peter, Hans-Hartmut; Eibel, Hermann

    2009-01-01

    B-cell survival depends on signals induced by B-cell activating factor (BAFF) binding to its receptor (BAFF-R). In mice, mutations in BAFF or BAFF-R cause B-cell lymphopenia and antibody deficiency. Analyzing BAFF-R expression and BAFF-binding to B cells in common variable immunodeficiency (CVID) patients, we identified two siblings carrying a homozygous deletion in the BAFF-R gene. Removing most of the BAFF-R transmembrane part, the deletion precludes BAFF-R expression. Without BAFF-R, B-cel...

  5. Measuring skewness of red blood cell deformability distribution by laser ektacytometry

    Energy Technology Data Exchange (ETDEWEB)

    Nikitin, S Yu; Priezzhev, A V; Lugovtsov, A E [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation); Ustinov, V D [M. V. Lomonosov Moscow State University, Faculty of Computational Mathematics and Cybernetics, Moscow (Russian Federation)

    2014-08-31

    An algorithm is proposed for measuring the parameters of red blood cell deformability distribution based on laser diffractometry of red blood cells in shear flow (ektacytometry). The algorithm is tested on specially prepared samples of rat blood. In these experiments we succeeded in measuring the mean deformability, deformability variance and skewness of red blood cell deformability distribution with errors of 10%, 15% and 35%, respectively. (laser biophotonics)

  6. Research opportunities in loss of red blood cell mass in space flight

    Science.gov (United States)

    Talbot, J. M.; Fisher, K. D.

    1985-01-01

    Decreases of red blood cell mass and plasma volume have been observed consistently following manned space flights. Losses of red cell mass by United States astronauts have averaged 10 to 15% (range: 2 to 21%). Based on postflight estimates of total hemoglobin, Soviet cosmonauts engaged in space missions lasting from 1 to 7 months have exhibited somewhat greater losses. Restoration of red cell mass requires from 4 to 6 weeks following return to Earth, regardless of the duration of space flight.

  7. Measurement of interaction forces between red blood cells in aggregates by optical tweezers

    Energy Technology Data Exchange (ETDEWEB)

    Maklygin, A Yu; Priezzhev, A V; Karmenian, A; Nikitin, Sergei Yu; Obolenskii, I S; Lugovtsov, Andrei E; Kisun Li

    2012-06-30

    We have fabricated double-beam optical tweezers and demonstrated the possibility of their use for measuring the interaction forces between red blood cells (erythrocytes). It has been established experimentally that prolonged trapping of red blood cells in a tightly focused laser beam does not cause any visible changes in their shape or size. We have measured the interaction between red blood cells in the aggregate, deformed by optical tweezers.

  8. Red blood cells serve as intravascular carriers of myeloperoxidase.

    Science.gov (United States)

    Adam, Matti; Gajdova, Silvie; Kolarova, Hana; Kubala, Lukas; Lau, Denise; Geisler, Anne; Ravekes, Thorben; Rudolph, Volker; Tsao, Philip S; Blankenberg, Stefan; Baldus, Stephan; Klinke, Anna

    2014-09-01

    Myeloperoxidase (MPO) is a heme enzyme abundantly expressed in polymorphonuclear neutrophils. MPO is enzymatically capable of catalyzing the generation of reactive oxygen species (ROS) and the consumption of nitric oxide (NO). Thus MPO has both potent microbicidal and, upon binding to the vessel wall, pro-inflammatory properties. Interestingly, MPO - a highly cationic protein - has been shown to bind to both endothelial cells and leukocyte membranes. Given the anionic surface charge of red blood cells, we investigated binding of MPO to erythrocytes. Red blood cells (RBCs) derived from patients with elevated MPO plasma levels showed significantly higher amounts of MPO by flow cytometry and ELISA than healthy controls. Heparin-induced MPO-release from patient-derived RBCs was significantly increased compared to controls. Ex vivo experiments revealed dose and time dependency for MPO-RBC binding, and immunofluorescence staining as well as confocal microscopy localized MPO-RBC interaction to the erythrocyte plasma membrane. NO-consumption by RBC-membrane fragments (erythrocyte "ghosts") increased with incrementally greater concentrations of MPO during incubation, indicating preserved catalytic MPO activity. In vivo infusion of MPO-loaded RBCs into C57BL/6J mice increased local MPO tissue concentrations in liver, spleen, lung, and heart tissue as well as within the cardiac vasculature. Further, NO-dependent relaxation of aortic rings was altered by RBC bound-MPO and systemic vascular resistance significantly increased after infusion of MPO-loaded RBCs into mice. In summary, we find that MPO binds to RBC membranes in vitro and in vivo, is transported by RBCs to remote sites in mice, and affects endothelial function as well as systemic vascular resistance. RBCs may avidly bind circulating MPO, and act as carriers of this leukocyte-derived enzyme.

  9. Haemoglobin and red cell counts in leptospirosis patients infected with different serovars

    Directory of Open Access Journals (Sweden)

    Scott Benjamin Craig

    2013-04-01

    Full Text Available Introduction The aim of the study was to compare haemoglobin and red cell counts between patients known to be infected with a range of leptospiral serovars. Methods The study retrospectively compared the haemoglobin and red cell count results from the first blood samples taken from 207 patients at presentation to a Queensland Health hospital. Results Significant differences were observed in haemoglobin and red cell counts in those infected with Leptospira interrogans serovars Szwajizak and Canicola when compared with most of the other serovars. Conclusions These findings suggest that haemoglobin and red cell counts may be useful in differentiating leptospiral serovars in leptospirosis patients.

  10. Storage time of red blood cells and mortality of transfusion recipients.

    Science.gov (United States)

    Middelburg, Rutger A; van de Watering, Leo M G; Briët, Ernest; van der Bom, Johanna G

    2013-01-01

    Storage of red cells and the associated storage lesion have been suggested to contribute to adverse clinical outcomes. The aim of this study was to investigate whether increasing storage time of red cells is associated with mortality of recipients. From all patients who received red cell transfusions between January 2005 and May 2009, in the Leiden University Medical Center, we selected those who received only-young or only-old red cells, defined as below or above the median storage time. Mortality was compared in a Cox regression model. Subsequently, similar comparisons were made between subgroups with increasing contrast between old and young red cells. Among adult patients, after correction for potential confounders, the hazard ratio of death within 1 year after receiving red cells stored for more than 17 days compared with 17 days or less was 0.98 (95% confidence interval, 0.83-1.2). With increasing contrast, the hazard ratio decreased to 0.56 (95% confidence interval, 0.32-0.97) for red cells stored for more than 24 days compared with less than 10 days. In contrast to what has previously been suggested, we find an almost 2-fold increase in mortality rate after the transfusion of fresh red cells compared with old red cells. Results dependent on analyses chosen and previous studies may not have used optimal analyses. The tendency to demand ever-fresher blood could actually be detrimental for at least some patient groups.

  11. The novel role of peroxiredoxin-2 in red cell membrane protein homeostasis and senescence.

    Science.gov (United States)

    Matté, Alessandro; Pantaleo, Antonella; Ferru, Emanuela; Turrini, Franco; Bertoldi, Mariarita; Lupo, Francesca; Siciliano, Angela; Ho Zoon, Chae; De Franceschi, Lucia

    2014-11-01

    Peroxiredoxin-2 (Prx2), a typical two-cysteine peroxiredoxin, is the third most abundant protein in red cells. Although progress has been made in the functional characterization of Prx2, its role in red cell membrane protein homeostasis is still under investigation. Here, we studied Prx2(-/-) mouse red cells. The absence of Prx2 promotes (i) activation of the oxidative-induced Syk pathway; (ii) increased band 3 Tyr phosphorylation, with clustered band 3; and (iii) increased heat shock protein (HSP27 and HSP70) membrane translocation. This was associated with enhanced in vitro erythrophagocytosis of Prx2(-/-) red cells and reduced Prx2(-/-) red cell survival, indicating the possible role of Prx2 membrane recruitment in red cell aging and in the clearance of oxidized hemoglobin and damaged proteins through microparticles. Indeed, we observed an increased release of microparticles from Prx2(-/-) mouse red cells. The mass spectrometric analysis of erythroid microparticles found hemoglobin chains, membrane proteins, and HSPs. To test these findings, we treated Prx2(-/-) mice with antioxidants in vivo. We observed that N-acetylcysteine reduced (i) Syk activation, (ii) band 3 clusterization, (iii) HSP27 membrane association, and (iv) erythroid microparticle release, resulting in increased Prx2(-/-) mouse red cell survival. Thus, we propose that Prx2 may play a cytoprotective role in red cell membrane protein homeostasis and senescence.

  12. Dynamics of Red Cells in Spleen: How Does Vesiculation Happen?

    Science.gov (United States)

    Zhu, Qiang; Salehyar, Sara; Cabrales, Pedro; Asaro, Robert

    2016-11-01

    Vesiculation of red blood cells as a result of local separation between lipid bilayer and cytoskeleton is known to happen in vivo, most likely inside spleen where they sustain large mechanical loads during the passage through venus slits. There is, however, little knowledge about the detailed scenario and condition. We address this question via a fluid-cell interaction model by coupling a multiscale model of the cell membrane (including molecular details) with a fluid dynamics model based on boundary-integral equations. A numerical flow channel is created where the cell is driven through a narrow slit by pressure (imitating the transit through venus slits in spleen). The concentration is the occurrence of large dissociation (negative) pressure between the skeleton/membrane connection that promotes separation, a precursor of vesicle formation. Critical levels for the negative pressure are estimated using published data. By following the maximum range of pressure, we conclude that for vesiculation to happen there must be biochemical influences (e.g. binding of degraded haemoglobin) that significantly reduce effective attachment density. This is consistent with reported trends in vesiculation that are believed to occur in cases of various hereditary anemias and during blood storage. Our findings also suggest the criticality of understanding the biochemical phenomena involved with cytoskeleton/membrane attachment.

  13. Axial dispersion in flowing red blood cell suspensions

    Science.gov (United States)

    Podgorski, Thomas; Losserand, Sylvain; Coupier, Gwennou

    2016-11-01

    A key parameter in blood microcirculation is the transit time of red blood cells (RBCs) through an organ, which can influence the efficiency of gas exchange and oxygen availability. A large dispersion of this transit time is observed in vivo and is partly due to the axial dispersion in the flowing suspension. In the classic Taylor-Aris example of a solute flowing in a tube, the combination of molecular diffusion and parabolic velocity profile leads to enhanced axial dispersion. In suspensions of non-Brownian deformable bodies such as RBCs, axial dispersion is governed by a combination of shear induced migration and shear-induced diffusion arising from hydrodynamic interactions. We revisit this problem in the case of RBC pulses flowing in a microchannel and show that the axial dispersion of the pulse eventually saturates with a final extension that depends directly on RBC mechanical properties. The result is especially interesting in the dilute limit since the final pulse length depends only on the channel width, exponent of the migration law and dimensionless migration velocity. In continuous flow, the dispersion of transit times is the result of complex cell-cell and cell-wall interactions and is strongy influenced by the polydispersity of the blood sample. The authors acknowledge support from LabEx TEC21 and CNES.

  14. Minimal RED Cell Pairs Markedly Improve Electrode Kinetics and Power Production in Microbial Reverse Electrodialysis Cells

    KAUST Repository

    Cusick, Roland D.

    2013-12-17

    Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m 2-cat) and wastewater (WW: 0.3 to 1.7 W/m2), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m2; WW: 1.9 W/m2). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m2-mem; WW: 1.7 W/m2) and 2-CP (Acetate: 1.3 W/m2-mem; WW: 0.6 W/m2) reactors were much higher than previous MRCs (0.3-0.5 W/m2-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment. © 2013 American Chemical Society.

  15. Minimal RED cell pairs markedly improve electrode kinetics and power production in microbial reverse electrodialysis cells.

    Science.gov (United States)

    Cusick, Roland D; Hatzell, Marta; Zhang, Fang; Logan, Bruce E

    2013-12-17

    Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m(2)-cat) and wastewater (WW: 0.3 to 1.7 W/m(2)), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m(2); WW: 1.9 W/m(2)). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m(2)-mem; WW: 1.7 W/m(2)) and 2-CP (Acetate: 1.3 W/m(2)-mem; WW: 0.6 W/m(2)) reactors were much higher than previous MRCs (0.3-0.5 W/m(2)-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment.

  16. Restrictive versus liberal transfusion strategy for red blood cell transfusion

    DEFF Research Database (Denmark)

    Holst, Lars B; Petersen, Marie W; Haase, Nicolai;

    2015-01-01

    OBJECTIVE: To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions. DESIGN: Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: Cochrane central register of controlled...... trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials....... TRIAL SELECTION: Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size. DATA EXTRACTION: Two authors independently screened...

  17. Magnetic nanoparticle effects on the red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Creanga, D E; Nadejde, C; Curecheriu, L [' Al. I. Cuza' University, Faculty of Physics, 11A Blvd. Carol I, Iasi (Romania)], E-mail: dorinacreanga@yahoo.com; Culea, M [' Babes Bolyai' University, Cluj-Napoca (Romania); Oancea, S [University of Veterinary Medicine ' I. Ionescu de la Brad' , Iasi (Romania); Racuciu, M [' Lucian Blaga' University, Sibiu (Romania)

    2009-05-01

    In vitro tests on magnetite colloidal nanoparticles effects upon animal red blood cells were carried out. Magnetite cores were stabilized with citric acid in the form of biocompatible magnetic fluid administrated in different dilutions in the whole blood samples. The hemolysis extent was found increased up to 2.75 in horse blood and respectively up to 2.81 in the dog blood. The electronic transitions assigned to the heme group were found shifted with about 500 cm{sup -1} or, respectively, affected by supplementary vibronic structures. The Raman vibrations assigned to oxyhemoglobin were much diminished in intensity probably due to the bonding of OH group from citrate shell to the heme iron ion.

  18. Magnetic nanoparticle effects on the red blood cells

    Science.gov (United States)

    Creangă, D. E.; Culea, M.; Nădejde, C.; Oancea, S.; Curecheriu, L.; Racuciu, M.

    2009-05-01

    In vitro tests on magnetite colloidal nanoparticles effects upon animal red blood cells were carried out. Magnetite cores were stabilized with citric acid in the form of biocompatible magnetic fluid administrated in different dilutions in the whole blood samples. The hemolysis extent was found increased up to 2.75 in horse blood and respectively up to 2.81 in the dog blood. The electronic transitions assigned to the heme group were found shifted with about 500 cm-1 or, respectively, affected by supplementary vibronic structures. The Raman vibrations assigned to oxyhemoglobin were much diminished in intensity probably due to the bonding of OH group from citrate shell to the heme iron ion.

  19. Red blood cell sodium transport in patients with cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Ulrik Lütken; Kiszka-Kanowitz, Marianne; Bendtsen, Flemming

    2016-01-01

    Patients with advanced cirrhosis have abnormal sodium homoeostasis. The study was undertaken to quantify the sodium transport across the plasma membrane of red blood cells (RBC) in patients with cirrhosis. RBC efflux and influx of sodium were studied in vitro with tracer (22) Na(+) according...... to linear kinetics in 24 patients with cirrhosis and 14 healthy controls. The sodium efflux was modified by ouabain (O), furosemide (F) and a combination of O and F (O + F). RBC sodium was significantly decreased (4·6 versus control 6·3 mmol l(-1) , Psodium (r = 0·57, P......sodium efflux was higher in patients with cirrhosis (+46%, Psodium buffers showed that the F-insensitive sodium efflux was twice as high in cirrhosis as in controls (P = 0...

  20. Simulation of red blood cell aggregation in shear flow.

    Science.gov (United States)

    Lim, B; Bascom, P A; Cobbold, R S

    1997-01-01

    A simulation model has been developed for red blood cell (RBC) aggregation in shear flow. It is based on a description of the collision rates of RBC, the probability of particles sticking together, and the breakage of aggregates by shear forces. The influence of shear rate, hematocrit, aggregate fractal dimension, and binding strength on aggregation kinetics were investigated and compared to other theoretical and experimental results. The model was used to simulate blood flow in a long large diameter tube under steady flow conditions at low Reynolds numbers. The time and spatial distribution of the state of aggregation are shown to be in qualitative agreement with previous B-mode ultrasound studies in which a central region of low echogenicity was noted. It is suggested that the model can provide a basis for interpreting prior measurements of ultrasound echogenicity and may help relate them to the local state of aggregation.

  1. Considerations of red blood cell molecular testing in transfusion medicine.

    Science.gov (United States)

    Svensson, Annika M; Delaney, Meghan

    2015-01-01

    The field of transfusion medicine is on the threshold of a paradigm shift, as the technology for genotyping of red blood cell antigens, including US FDA-approved arrays, is now moving into standard practice. Access to cost-efficient, high-resolution genotyping has the potential to increase the quality of care by decreasing the risk for alloimmunization and incompatible transfusions in individuals on long-term blood transfusion protocols, including patient groups with hemoglobinopathies and other chronic diseases. Current and future applications of molecular methods in transfusion medicine and blood banking are discussed, with emphasis on indications for genotyping in various clinical scenarios. Furthermore, limitations of the current gold standard methodology and serology, as well as of contemporary molecular methodology, are examined.

  2. Duration of red blood cell storage and inflammatory marker generation

    Science.gov (United States)

    Sut, Caroline; Tariket, Sofiane; Chou, Ming Li; Garraud, Olivier; Laradi, Sandrine; Hamzeh-Cognasse, Hind; Seghatchian, Jerard; Burnouf, Thierry; Cognasse, Fabrice

    2017-01-01

    Red blood cell (RBC) transfusion is a life-saving treatment for several pathologies. RBCs for transfusion are stored refrigerated in a preservative solution, which extends their shelf-life for up to 42 days. During storage, the RBCs endure abundant physicochemical changes, named RBC storage lesions, which affect the overall quality standard, the functional integrity and in vivo survival of the transfused RBCs. Some of the changes occurring in the early stages of the storage period (for approximately two weeks) are reversible but become irreversible later on as the storage is extended. In this review, we aim to decipher the duration of RBC storage and inflammatory marker generation. This phenomenon is included as one of the causes of transfusion-related immunomodulation (TRIM), an emerging concept developed to potentially elucidate numerous clinical observations that suggest that RBC transfusion is associated with increased inflammatory events or effects with clinical consequence. PMID:28263172

  3. Mobility Enhancement of Red Blood Cells with Biopolymers

    Science.gov (United States)

    Tahara, Daiki; Oikawa, Noriko; Kurita, Rei

    2016-03-01

    Adhesion of red blood cells (RBC) to substrates are one of crucial problems for a blood clot. Here we investigate the mobility of RBC between two glass substrates in saline with polymer systems. We find that RBCs are adhered to the glass substrate with PEG, however the mobility steeply increases with fibrinogen and dextran, which are biopolymers. We also find that the mobility affects an aggregation dynamics of RBCs, which is related with diseases such as influenza, blood clot and so on. The Brownian motion helps to increase probability of contact with each other and to find a more stable condition of the aggregation. Thus the biopolymers play important roles not only for preventing the adhesion but also for the aggregation.

  4. Stretching Behavior of Red Blood Cells at High Strain Rates

    Science.gov (United States)

    Mancuso, Jordan; Ristenpart, William

    2016-11-01

    Most work on the mechanical behavior of red blood cells (RBCs) has focused on simple shear flows. Relatively little work has examined RBC deformations in the physiologically important extensional flow that occurs at the entrance to a constriction. In particular, previous work suggests that RBCs rapidly stretch out and then retract upon entering the constriction, but to date no model predicts this behavior for the extremely high strain rates typically experienced there. In this work, we use high speed video to perform systematic measurements of the dynamic stretching behavior of RBCs as they enter a microfluidic constriction. We demonstrate that a simple viscoelastic model captures the observed stretching dynamics, up to strain rates as high as 1000 s-1. The results indicate that the effective elastic modulus of the RBC membrane at these strain rates is an order of magnitude larger than moduli measured by micropipette aspiration or other low strain rate techniques.

  5. Pure red cell aplasia following autoimmune hemolytic anemia: An enigma

    Directory of Open Access Journals (Sweden)

    M Saha

    2013-01-01

    Full Text Available A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA, prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  6. Pure red cell aplasia following autoimmune hemolytic anemia: an enigma.

    Science.gov (United States)

    Saha, M; Ray, S; Kundu, S; Chakrabarti, P

    2013-01-01

    A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA), prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA) showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  7. Autoimmune Hemolytic Anemia and Red Blood Cell Autoantibodies.

    Science.gov (United States)

    Quist, Erin; Koepsell, Scott

    2015-11-01

    Autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell (RBC) antibodies that destroy RBCs. Although autoimmune hemolytic anemia is rare, RBC autoantibodies are encountered frequently and can complicate transfusion workups, impede RBC alloantibody identification, delay distribution of compatible units, have variable clinical significance that ranges from benign to life-threatening, and may signal an underlying disease or disorder. In this review, we discuss the common presenting features of RBC autoantibodies, laboratory findings, ancillary studies that help the pathologist investigate the clinical significance of autoantibodies, and how to provide appropriate patient care and consultation for clinical colleagues. Pathologists must be mindful of, and knowledgeable about, this entity because it not only allows for direct clinical management but also can afford an opportunity to preemptively treat an otherwise silent malignancy or disorder.

  8. P2X and P2Y receptor signaling in red blood cells.

    Science.gov (United States)

    Sluyter, Ronald

    2015-01-01

    Purinergic signaling involves the activation of cell surface P1 and P2 receptors by extracellular nucleosides and nucleotides such as adenosine and adenosine triphosphate (ATP), respectively. P2 receptors comprise P2X and P2Y receptors, and have well-established roles in leukocyte and platelet biology. Emerging evidence indicates important roles for these receptors in red blood cells. P2 receptor activation stimulates a number of signaling pathways in progenitor red blood cells resulting in microparticle release, reactive oxygen species formation, and apoptosis. Likewise, activation of P2 receptors in mature red blood cells stimulates signaling pathways mediating volume regulation, eicosanoid release, phosphatidylserine exposure, hemolysis, impaired ATP release, and susceptibility or resistance to infection. This review summarizes the distribution of P2 receptors in red blood cells, and outlines the functions of P2 receptor signaling in these cells and its implications in red blood cell biology.

  9. P2X and P2Y receptor signaling in red blood cells

    Directory of Open Access Journals (Sweden)

    Ronald eSluyter

    2015-10-01

    Full Text Available Purinergic signaling involves the activation of cell surface P1 and P2 receptors by extracellular nucleosides and nucleotides such as adenosine and adenosine triphosphate (ATP, respectively. P2 receptors comprise P2X and P2Y receptors, and have well-established roles in leukocyte and platelet biology. Emerging evidence indicates important roles for these receptors in red blood cells. P2 receptor activation stimulates a number of signaling pathways in progenitor red blood cells resulting in microparticle release, reactive oxygen species formation and apoptosis. Likewise, activation of P2 receptors in mature red blood cells stimulates signaling pathways mediating volume regulation, eicosanoid release, phosphatidylserine exposure, hemolysis, impaired ATP release, and susceptibility or resistance to infection. This review summarizes the distribution of P2 receptors in red blood cells, and outlines the functions of P2 receptor signaling in these cells and its implications in red blood cell biology.

  10. Clinical utility of flow cytometry in the study of erythropoiesis and nonclonal red cell disorders.

    Science.gov (United States)

    Chesney, Alden; Good, David; Reis, Marciano

    2011-01-01

    Erythropoiesis involves proliferation and differentiation of small population of hematopoietic stem cells resident in the bone marrow into mature red blood cells. The determination of the cellular composition of the blood is a valuable tool in the diagnosis of diseases and monitoring of therapy. Flow cytometric analysis is increasingly being used to characterize the heterogeneous cell populations present in the blood and the hematopoietic cell differentiation and maturation pathways of the bone marrow. Here we discuss the role of flow cytometry in the study of erythropoiesis and nonclonal red blood cell disorders. First, we discuss flow cytometric analysis of reticulocytes. Next, we review salient quantitative methods that can be used for detection of fetal-maternal hemorrhage (FMH). We also discuss flow cytometric analysis of high hemoglobin F (HbF) in Sickle Cell Disease (SCD), hereditary spherocytosis (HS), red cell survival and red cell volume. We conclude by discussing cell cycle of erythroid cells.

  11. [Molecular basis of red blood cell adhesion to endothelium].

    Science.gov (United States)

    Wautier, J-L; Wautier, M-P

    2011-01-01

    The extent of red blood cell adhesion is correlated with the incidence of vascular complications and the severity of the disease. Patients with sickle cell anemia (HbSS) experience vasoocclusive episodes. The adhesion of RBCs from HbSS patients is increased and related to VLA-4 exposure, which binds to vascular cell adhesion molecule (VCAM-1). Inter Cellular Adhesion Molecule (ICAM-1), CD31, CD36 and glycans are potential receptors for PfEMP1 of RBCs parasited by plasmodium falciparum. The incidence of vascular complications is very high in patients with diabetes mellitus. RBC adhesion is increased and statistically correlated with the severity of the angiopathy. Glycation of RBC membrane proteins is responsible for binding to the receptor for advanced glycation end products (RAGE). Polycythemia Vera (PV) is the most frequent myeloproliferative disorder and characterized by a high occurrence of thrombosis of mesenteric and cerebral vessels. PV is due to a mutation of the Janus kinase 2 (JAK2 V617F). This mutation stimulates erythropoiesis and is the cause of Lu/BCAM (CD239) phosphorylation, which potentiated the interaction with laminin alpha 5. The couple laminin alpha 5 endothelial and phosphorylated Lu/BCAM explained the increased adhesion of RBCs from patients PV to endothelium.

  12. A multiscale model for red blood cell mechanics.

    Science.gov (United States)

    Hartmann, Dirk

    2010-02-01

    The objective of this article is the derivation of a continuum model for mechanics of red blood cells via multiscale analysis. On the microscopic level, we consider realistic discrete models in terms of energy functionals defined on networks/lattices. Using concepts of Gamma-convergence, convergence results as well as explicit homogenisation formulae are derived. Based on a characterisation via energy functionals, appropriate macroscopic stress-strain relationships (constitutive equations) can be determined. Further, mechanical moduli of the derived macroscopic continuum model are directly related to microscopic moduli. As a test case we consider optical tweezers experiments, one of the most common experiments to study mechanical properties of cells. Our simulations of the derived continuum model are based on finite element methods and account explicitly for membrane mechanics and its coupling with bulk mechanics. Since the discretisation of the continuum model can be chosen freely, rather than it is given by the topology of the microscopic cytoskeletal network, the approach allows a significant reduction of computational efforts. Our approach is highly flexible and can be generalised to many other cell models, also including biochemical control.

  13. Why does the mammalian red blood cell have aquaporins?

    Science.gov (United States)

    Kuchel, Philip W; Benga, Gheorghe

    2005-11-01

    Aquaporins are now known to mediate the rapid exchange of water across the plasma membranes of diverse cell types. This exchange has been studied and kinetically characterized in red blood cells (erythrocytes; RBC) from many animal species. In recent years, a favoured method has been one based on NMR spectroscopy. Despite knowledge of their molecular structure the physiological raison d' etre of aquaporins in RBCs is still only speculated upon. Here, we present two hypotheses that account for the fact that the exchange of water is so fast in RBCs. The first is denoted the "oscillating sieve" hypothesis and it posits that known membrane undulations at frequencies up to 30 Hz with displacements up to 0.3 microm are energetically favoured by the high water permeability of the membrane. The second denoted the "water displacement" hypothesis is based on the known rapid exchange across the RBC membrane of ions such as Cl- and HCO3- and solutes such as glucose, all of whose molecular volumes are significantly greater than that of water. The ideas are generalizable to other cell types and organelles.

  14. Manipulation of red blood cells with electric field

    Science.gov (United States)

    Saboonchi, Hossain; Esmaeeli, Asghar

    2009-11-01

    Manipulation of bioparticles and macromolecules is the central task in many biological and biotechnological processes. The current methods for physical manipulation takes advantage of different forces such as acoustic, centrifugal, magnetic, electromagnetic, and electric forces, as well as using optical tweezers or filtration. Among all these methods, however, the electrical forces are particularly attractive because of their favorable scale up with the system size which makes them well-suited for miniaturization. Currently the electric field is used for transportation, poration, fusion, rotation, and separation of biological cells. The aim of the current research is to gain fundamental understanding of the effect of electric field on the human red blood cells (RBCs) using direct numerical simulation. A front tracking/finite difference technique is used to solve the fluid flow and electric field equations, where the fluid in the cell and the blood (plasma) is modeled as Newtonian and incompressible, and the interface separating the two is treated as an elastic membrane. The behavior of RBCs is investigated as a function of the controlling parameters of the problem such as the strength of the electric field.

  15. Pure Red Cell Aplasia and Lymphoproliferative Disorders: An Infrequent Association

    Directory of Open Access Journals (Sweden)

    Efthymia Vlachaki

    2012-01-01

    Full Text Available Pure red cell aplasia (PRCA is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL or non-Hodgkin lymphoma (NHL. The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.

  16. Pure red cell aplasia and lymphoproliferative disorders: an infrequent association.

    Science.gov (United States)

    Vlachaki, Efthymia; Diamantidis, Michael D; Klonizakis, Philippos; Haralambidou-Vranitsa, Styliani; Ioannidou-Papagiannaki, Elizabeth; Klonizakis, Ioannis

    2012-01-01

    Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.

  17. Peripheral red blood cell split chimerism as a consequence of intramedullary selective apoptosis of recipient red blood cells in a case of sickle cell disease.

    Science.gov (United States)

    Marziali, Marco; Isgrò, Antonella; Sodani, Pietro; Gaziev, Javid; Fraboni, Daniela; Paciaroni, Katia; Gallucci, Cristiano; Alfieri, Cecilia; Roveda, Andrea; De Angelis, Gioia; Cardarelli, Luisa; Ribersani, Michela; Andreani, Marco; Lucarelli, Guido

    2014-01-01

    Allogeneic cellular gene therapy through hematopoietic stem cell transplantation is the only radical cure for congenital hemoglobinopathies like thalassemia and sickle cell anemia. Persistent mixed hematopoietic chimerism (PMC) has been described in thalassemia and sickle cell anemia. Here, we describe the clinical course of a 6-year-old girl who had received bone marrow transplant for sickle cell anemia. After the transplant, the patient showed 36% donor hematopoietic stem cells in the bone marrow, whereas in the peripheral blood there was evidence of 80% circulating donor red blood cells (RBC). The analysis of apoptosis at the Bone Marrow level suggests that Fas might contribute to the cell death of host erythroid precursors. The increase in NK cells and the regulatory T cell population observed in this patient suggests that these cells might contribute to the condition of mixed chimerism.

  18. Peripheral Red Blood Cell Split Chimerism as a Consequence of Intramedullary Selective Apoptosis of Recipient Red Blood Cells in a Case of Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Marco Marziali

    2014-08-01

    Full Text Available Allogeneic cellular gene therapy through hematopoietic stem cell transplantation is the only radical cure for congenital hemoglobinopathies like thalassemia and sickle cell anemia. Persistent mixed hematopoietic chimerism (PMC has been described in thalassemia and sickle cell anemia. Here, we describe the clinical course of a 6-year-old girl who had received bone marrow transplant for sickle cell anemia. After the transplant, the patient showed 36% donor hematopoietic stem cells in the bone marrow, whereas in the peripheral blood there was evidence of 80%  circulating donor red blood cells (RBC. The analysis of apoptosis at the Bone Marrow  level suggests that Fas might contribute to the cell death of host erythroid precursors. The increase in NK cells and the regulatory T cell population observed in this patient suggests that these cells might contribute to the condition of mixed chimerism.

  19. The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology

    Directory of Open Access Journals (Sweden)

    Kamil Bujak

    2015-01-01

    Full Text Available Red blood cell distribution width (RDW is a measure of red blood cell volume variations (anisocytosis and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD. In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis. Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization.

  20. The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology

    Science.gov (United States)

    Bujak, Kamil; Wasilewski, Jarosław; Osadnik, Tadeusz; Jonczyk, Sandra; Kołodziejska, Aleksandra; Gierlotka, Marek; Gąsior, Mariusz

    2015-01-01

    Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization. PMID:26379362

  1. Red wine triggers cell death and thioredoxin reductase inhibition: effects beyond resveratrol and SIRT1.

    Science.gov (United States)

    Wallenborg, Karolina; Vlachos, Pinelopi; Eriksson, Sofi; Huijbregts, Lukas; Arnér, Elias S J; Joseph, Bertrand; Hermanson, Ola

    2009-05-01

    Red wine contains antioxidants and is at moderate amounts believed to exert certain positive health effects. Resveratrol is one of the most studied antioxidants in red wine and has been suggested to activate the longevity- and metabolism-associated histone deacetylase SIRT1. Here we show that relatively low concentrations of resveratrol (0.5-3 microM) specifically inhibited neuronal differentiation of neural stem cells in a SIRT1-dependent manner whereas higher concentrations of resveratrol (> or =10 microM) induced a SIRT1-independent cell death. Surprisingly, using a cell based assay, we found that small amounts of red wine (1-5% v/v)--but not white wine--induced a massive and rapid cell death of various cell types, including neural stem cells and several cancer cell lines. This red wine-induced cell death was ethanol-, SIRT1- and resveratrol-independent but associated with increased oxidative stress and inhibition of thioredoxin reductase (TrxR) activity. The TrxR inhibition correlated with the red color (absorbance at 520 nm) of the wines demonstrating that pigment components of red wine can exert profound cellular effects. Our results unveil important roles for SIRT1 and TrxR in resveratrol and red wine-mediated effects on progenitor and cancer cells, and demonstrate that cellular responses to red wine may be more complex than generally appreciated.

  2. Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES.

    Science.gov (United States)

    Bokori-Brown, Monika; Petrov, Peter G; Khafaji, Mawya A; Mughal, Muhammad K; Naylor, Claire E; Shore, Angela C; Gooding, Kim M; Casanova, Francesco; Mitchell, Tim J; Titball, Richard W; Winlove, C Peter

    2016-05-06

    This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling, and artificial cell aging modulate the cell response to the toxin. We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated hemoglobin and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes. Finally, we show that diabetic red blood cells are more resistant to pneumolysin and the related toxin perfringolysin O relative to healthy red blood cells. Taken together, these studies indicate that the diversity of cell response to pneumolysin within a population of human red blood cells is influenced by the biophysical and biochemical status of the plasma membrane and the chemical and/or oxidative stress pre-history of the cell.

  3. BMP2 rescues deficient cell migration in Tgfbr3(-/-) epicardial cells and requires Src kinase.

    Science.gov (United States)

    Allison, Patrick; Espiritu, Daniella; Camenisch, Todd D

    2016-05-03

    During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. The type III transforming growth factor-β receptor (TGFβR3) is required for epicardial cell invasion and development of coronary vasculature in vivo. Bone Morphogenic Protein-2 (BMP2) is a driver of epicardial cell migration. Utilizing a primary epicardial cell line derived from Tgfbr3(+/+) and Tgfbr3(-/-) mouse embryos, we show that Tgfbr3(-/-) epicardial cells are deficient in BMP2 mRNA expression. Tgfbr3(-/-) epicardial cells are deficient in 2-dimensional migration relative to Tgfbr3(+/+) cells; BMP2 induces cellular migration to Tgfbr3(+/+) levels without affecting proliferation. We further demonstrate that Src kinase activity is required for BMP2 driven Tgfbr3(-/-) migration. BMP2 also requires Src for filamentous actin polymerization in Tgfbr3(-/-) epicardial cells. Taken together, our data identifies a novel pathway in epicardial cell migration required for development of the coronary vessels.

  4. Red blood cells and thrombin generation in sickle cell disease.

    Science.gov (United States)

    Whelihan, Matthew F; Lim, Ming Y; Key, Nigel S

    2014-05-01

    The prothrombotic nature of sickle cell disease (SCD) is evidenced by the chronically elevated levels of almost all coagulation activation biomarkers, and an increased incidence of certain thrombotic events, including venous thromboembolism. Numerous studies have attempted to define the extent and elucidate the mechanism of the observed increase in thrombin generation in SCD patients in vivo. In general, these studies were performed using thrombin generation assays in platelet poor or platelet rich plasma and showed little difference in endogenous thrombin potential between the SCD cohort and healthy matched controls. In SCD, erythrocytes and monocytes have been demonstrated to exhibit procoagulant characteristics. Thus, the absence of these cellular components in standard thrombin generation assays may fail to reflect global hypercoagulability in the whole blood of patients with SCD. We were therefore surprised to see no difference in net thrombin generation in tissue factor-initiated initiated clotting of whole blood from patients with SCD. However, we are continuing to reconcile these seemingly disparate observations by slight modifications of the whole blood model that include alternative coagulation triggers and a re-examination of the net thrombin generation when the protein/protein S system is simultaneously interrogated.

  5. Molecular mechanisms underlying synergistic adhesion of sickle red blood cells by hypoxia and low nitric oxide bioavailability.

    Science.gov (United States)

    Gutsaeva, Diana R; Montero-Huerta, Pedro; Parkerson, James B; Yerigenahally, Shobha D; Ikuta, Tohru; Head, C Alvin

    2014-03-20

    The molecular mechanisms by which nitric oxide (NO) bioavailability modulates the clinical expression of sickle cell disease (SCD) remain elusive. We investigated the effect of hypoxia and NO bioavailability on sickle red blood cell (sRBC) adhesion using mice deficient for endothelial NO synthase (eNOS) because their NO metabolite levels are similar to those of SCD mice but without hypoxemia. Whereas sRBC adhesion to endothelial cells in eNOS-deficient mice was synergistically upregulated at the onset of hypoxia, leukocyte adhesion was unaffected. Restoring NO metabolite levels to physiological levels markedly reduced sRBC adhesion to levels seen under normoxia. These results indicate that sRBC adherence to endothelial cells increases in response to hypoxia prior to leukocyte adherence, and that low NO bioavailability synergistically upregulates sRBC adhesion under hypoxia. Although multiple adhesion molecules mediate sRBC adhesion, we found a central role for P-selectin in sRBC adhesion. Hypoxia and low NO bioavailability upregulated P-selectin expression in endothelial cells in an additive manner through p38 kinase pathways. These results demonstrate novel cellular and signaling mechanisms that regulate sRBC adhesion under hypoxia and low NO bioavailability. Importantly, these findings point us toward new molecular targets to inhibit cell adhesion in SCD.

  6. NHE-1 sequence and expression in toad, snake and fish red blood cells

    DEFF Research Database (Denmark)

    Thomsen, Steffen Nyegaard; Wang, Tobias; Kristensen, Torsten

    Red blood cells (RBC) from reptiles appear not to express regulatory volume increase (RVI) upon shrinkage (Kristensen et al., 2008). In other vertebrates, the RVI response is primarily mediated by activation of the Na+/H+ exchanger (NHE-1) and we, therefore decided to investigate whether red cell...

  7. The effects of non-leukoreduced red blood cell transfusions on microcirculation in mixed surgical patients.

    NARCIS (Netherlands)

    Ayhan, B.; Yuruk, K.; Koene, S.; Sahin, A.; Ince, C.; Aypar, U.

    2013-01-01

    BACKGROUND: The impact of the storage process on oxygen-carrying properties of red blood cells and the efficacy of red blood cell (RBC) transfusions concerning tissue oxygenation remain an issue of debate in transfusion medicine. Storage time and leukocyte content probably interact since longer stor

  8. Evaluation of an additive solution for preservation of canine red blood cells.

    Science.gov (United States)

    Wardrop, K J; Owen, T J; Meyers, K M

    1994-01-01

    The effect of an additive preservative solution on canine red blood cell posttransfusion viability (PTV) and on selected canine red blood cell biochemical parameters was studied. One unit (450 mL) of blood was collected from 6 clinically normal dogs into the anticoagulant citrate phosphate dextrose, centrifuged, and the plasma removed. The red blood cells were then suspended in 100 mL of a saline, adenine, dextrose, and mannitol solution and stored at 4 degrees C. Aliquots were removed for study at 1, 10, 20, 30, 37, and 44 days. The 24-hour PTV of autologous red blood cells was determined using a sodium chromate (51Cr) label. Red blood cell concentrations of 2,3-diphosphoglycerate (2,3-DPG), adenosine-5'-triphosphate (ATP), and pH were also determined. Canine red blood cell PTV, pH, ATP, and 2,3-DPG concentrations decreased during storage (P Food and Drug Administration (FDA) minimum standard for human red blood cells, the PTV was substandard in 75% of the day 44 units. The FDA standard was exceeded in 83% of the day 37 units. It was concluded that 37-day-old canine red blood cells preserved with a saline, adenine, dextrose, and mannitol solution are of acceptable quality for transfusion.

  9. Cryopreserved packed red blood cells in surgical patients: past, present, and future.

    Science.gov (United States)

    Chang, Alex; Kim, Young; Hoehn, Richard; Jernigan, Peter; Pritts, Timothy

    2016-09-08

    Since the advent of anticoagulation and component storage of human blood products, allogeneic red blood cell transfusion has been one of the most common practices in modern medicine. Efforts to reduce the biochemical effects of storage, collectively known as the red blood cell storage lesion, and prolong the storage duration have led to numerous advancements in erythrocyte storage solutions. Cryopreservation and frozen storage of red blood cells in glycerol have been successfully utilised by many civilian and military institutions worldwide. Through progressive improvements in liquid storage of erythrocytes in novel storage solutions, the logistical need for cryopreserved red blood cells in the civilian setting has diminished. A growing body of current literature is focused on the clinical consequences of packed red blood cell age. Modern cryopreservation techniques show promise as a cost-effective method to ameliorate the negative effect of the red blood cell storage lesion, while meeting the technical and logistical needs of both civilian and military medicine. This review outlines the history of red blood cell cryopreservation, the clinical impact of red cell storage, and highlights the current literature on frozen blood and its impact on modern transfusion.

  10. Preoperative factors associated with red blood cell transfusion in hip fracture patients

    DEFF Research Database (Denmark)

    Madsen, Christian Medom; Jørgensen, Henrik Løvendahl; Norgaard, Astrid

    2014-01-01

    Red blood cell (RBC) transfusion is a frequently used treatment in patients admitted with a fractured hip, but the use remains an area of much debate. The aim of this study was to determine preoperative factors associated with the risk of receiving a red blood cell transfusion in hip fracture...

  11. Quantification of the fraction poorly deformable red blood cells using ektacytometry

    NARCIS (Netherlands)

    Streekstra, G.J.; Dobbe, J.G.G.; Hoekstra, A.G.

    2010-01-01

    We describe a method to obtain the fraction of poorly deformable red blood cells in a blood sample from the intensity pattern in an ektacytometer. In an ektacytometer red blood cells are transformed into ellipsoids by a shear flow between two transparent cylinders. The intensity pattern, due to a la

  12. On the shape memory of red blood cells

    Science.gov (United States)

    Cordasco, Daniel; Bagchi, Prosenjit

    2017-04-01

    Red blood cells (RBCs) undergo remarkably large deformations when subjected to external forces but return to their biconcave discoid resting shape as the forces are withdrawn. In many experiments, such as when RBCs are subjected to a shear flow and undergo the tank-treading motion, the membrane elements are also displaced from their original (resting) locations along the cell surface with respect to the cell axis, in addition to the cell being deformed. A shape memory is said to exist if after the flow is stopped the RBC regains its biconcave shape and the membrane elements also return to their original locations. The shape memory of RBCs was demonstrated by Fischer ["Shape memory of human red blood cells," Biophys. J. 86, 3304-3313 (2004)] using shear flow go-and-stop experiments. Optical tweezer and micropipette based stretch-relaxation experiments do not reveal the complete shape memory because while the RBC may be deformed, the membrane elements are not significantly displaced from their original locations with respect to the cell axis. Here we present the first three-dimensional computational study predicting the complete shape memory of RBCs using shear flow go-and-stop simulations. The influence of different parameters, namely, membrane shear elasticity and bending rigidity, membrane viscosity, cytoplasmic and suspending fluid viscosity, as well as different stress-free states of the RBC is studied. For all cases, the RBCs always exhibit shape memory. The complete recovery of the RBC in shear flow go-and-stop simulations occurs over a time that is orders of magnitude longer than that for optical tweezer and micropipette based relaxations. The response is also observed to be more complex and composed of widely disparate time scales as opposed to only one time scale that characterizes the optical tweezer and micropipette based relaxations. We observe that the recovery occurs in three phases: a rapid compression of the RBC immediately after the flow is stopped

  13. The relationship between stroke mortality and red blood cell parameters.

    Directory of Open Access Journals (Sweden)

    Hamidreza Hatamian

    2014-12-01

    Full Text Available Several factors influence on the outcome of ischemic stroke. The aim of this study was determination the relationship between stroke mortality and red blood cell parameters.This cross-sectional study was conducted from 2011 July to June 2012. For all patients with ischemic stroke in middle cerebral artery (MCA territory, the cell blood count test was performed. We recorded their mortality on the 1(st week and the 1(st month after ischemic stroke. Data analysis was performed using t-test, χ(2, Mann-Whitney U-test, logistic regression and receiver operating characteristic curve in SPSS for Windows 19.0.A total of 98 subjects (45.9% men and 54.1% women with the mean age of 71.0 ± 13.9 years were assessed, while 67.3% of them were anemic. The prevalence of 1(st week mortality among anemic and non-anemic patients was 40.9% and 34.4% (P = 0.534. The prevalence of mortality after 1(st week till 1(st month was 19.6% and 21.0% respectively (P = 0.636. In univariant analysis, only 1(st month mortality had a significant relationship with red blood cell (RBC count (P = 0.022. However, the result of logistic regression model showed that RBC (P = 0.012 and mean corpuscular volume (MCV (P = 0.021 remained as predictors of the 1(st week and the 1(st month mortality (P = 0.011 and P = 0.090 respectively. The best cutoff point of RBC for the prediction of the 1(st week mortality with 44.7% specificity and 69.5% sensitivity was estimated 4.07 million/μl and for the 1(st month mortality with 46.6% specificity and 72.2% sensitivity was estimated 4.16 million/μl.The RBC count and MCV are independent predictors of ischemic stroke short-term mortality.

  14. Red cell distribution width in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Nada AM

    2015-10-01

    Full Text Available Aml Mohamed Nada Department of Internal Medicine, Unit of Endocrinology, Diabetes and Metabolism, Faculty of Medicine, Mansoura University, Mansoura, Egypt Objective: To study the indices of some elements of the complete blood count, in type 2 diabetic patients, in comparison with nondiabetic healthy controls; and to find out the effects of glycemic control and different medications on these indices. To the best of our knowledge, this study is novel in our environment and will serve as a foundation for other researchers in this field. Methods: This retrospective study included 260 type 2 diabetic patients on treatment and 44 healthy control subjects. Sex, age, weight, height, blood pressure, complete blood count, fasting plasma glucose, hemoglobin A1c (HbA1c, and lipid profile data, were available for all of the study population. For diabetic patients, data on duration of diabetes and all medications were also available. Results: Red cell distribution width (RDW was significantly higher in diabetic patients than in control subjects (P=0.008. It was also higher in patients with uncontrolled glycemia (HbA1c >7% than those with good control (HbA1c ≤7%; P=0.035. Mean platelet volume (MPV was comparable in both diabetic patients and healthy controls (P=0.238. RDW and MPV did not significantly correlate with fasting plasma glucose, HbA1c, or duration of diabetes. Both aspirin and clopidogrel did not show a significant effect on MPV. Both insulin and oral hypoglycemic agents did not show a significant effect on RDW, mean corpuscular volume, MPV, platelet count, or white blood cell count. Diabetic patients treated with indapamide or the combined thiazides and angiotensin receptor blockers showed no significant difference in RDW when compared with the control subjects. Conclusion: RDW, which is recently considered as an inflammatory marker with a significant predictive value of mortality in diseased and healthy populations, is significantly higher in

  15. Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice.

    Directory of Open Access Journals (Sweden)

    Carl Johan Drott

    Full Text Available Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1, that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.

  16. Measurement of posttransfusion red cell survival with the biotin label.

    Science.gov (United States)

    Mock, Donald M; Widness, John A; Veng-Pedersen, Peter; Strauss, Ronald G; Cancelas, Jose A; Cohen, Robert M; Lindsell, Christopher J; Franco, Robert S

    2014-07-01

    The goal of this review is to summarize and critically assess information concerning the biotin method to label red blood cells (RBC) for use in studies of RBC and transfusion biology-information that will prove useful to a broad audience of clinicians and scientists. A review of RBC biology, with emphasis on RBC senescence and in vivo survival, is included, followed by an analysis of the advantages and disadvantages of biotin-labeled RBC (BioRBC) for measuring circulating RBC volume, posttransfusion RBC recovery, RBC life span, and RBC age-dependent properties. The advantages of BioRBC over (51)Cr RBC labeling, the current reference method, are discussed. Because the biotin method is straightforward and robust, including the ability to follow the entire life spans of multiple RBC populations concurrently in the same subject, BioRBC offers distinct advantages for studying RBC biology and physiology, particularly RBC survival. The method for biotin labeling, validation of the method, and application of BioRBCs to studies of sickle cell disease, diabetes, and anemia of prematurity are reviewed. Studies documenting the safe use of BioRBC are reviewed; unanswered questions requiring future studies, remaining concerns, and regulatory barriers to broader application of BioRBC including adoption as a new reference method are also presented.

  17. Dynamics of Red Blood Cells through submicronic splenic slits

    Science.gov (United States)

    Helfer, Emmanuele; Gambhire, Priya; Atwell, Scott; Bedu, Frederic; Ozerov, Igor; Viallat, Annie; Charrier, Anne; Badens, Catherine; Centre de reference Thalassemie, Badens Team; Physics; Engineering of Living Systems Team

    2016-11-01

    Red Blood Cells (RBCs) are periodically monitored for changes in their deformability by the spleen, and are entrapped and destroyed if unable to pass through the splenic interendothelial slits (IESs). In particular, in sickle cell disease (SCD), where hemoglobin form fibers inside the RBCs, and in hereditary spherocytosis (HS), where RBCs are more spherical and membrane-cytoskekeleton bonds are weakened, the loss of RBC deformability leads to spleen dysfunction. By combining photolithography and anisotropic wet etching techniques, we developed a new on-chip PDMS device with channels replicating the submicronic physiological dimensions of IESs to study the mechanisms of deformation of the RBCs during their passage through these biomimetic slits. For the first time, with HS RBCs, we show the disruption of the links between the RBC membrane and the underlying spectrin network. In the case of SCD RBCs we show the appearance of a tip at the front of the RBC with a longer time relaxation due to the increased cytoplasmic viscosity. This work has been carried out thanks to the support of the A*MIDEX project (n° ANR-11-IDEX-0001-02) funded by the «Investissements d'Avenir». French Government program, managed by ANR.

  18. Invasive thymoma with pure red cell aplasia and amegakaryocytic thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Takuya Onuki

    2016-12-01

    Full Text Available We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL, thrombocytopenia (platelet count, 0.6×104/μL, and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA and acquired amegakaryocytic thrombocytopenia (AAMT. On Day 8 of admission, the patient received immunosuppressive therapy together with cyclosporine for the 2 severe hematologic diseases, which were stabilized within 2 months. Subsequently, total thymectomy was performed. The diagnosis of the tumor invading the left lung was invasive thymoma, Masaoka- Koga stage III. The histological diagnosis was World Health Organization type AB. Thymoma accompanied with PRCA and AAMT is very rare, and, based on our case, immunotherapeutic therapy for the hematologic disorders should precede surgical intervention.

  19. ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression

    Science.gov (United States)

    Aryal, Binod; Rotllan, Noemi; Araldi, Elisa; Ramírez, Cristina M.; He, Shun; Chousterman, Benjamin G.; Fenn, Ashley M.; Wanschel, Amarylis; Madrigal-Matute, Julio; Warrier, Nikhil; Martín-Ventura, Jose L.; Swirski, Filip K.; Suárez, Yajaira; Fernández-Hernando, Carlos

    2016-07-01

    Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population. ANGPTL4-deficient CMPs have higher lipid raft content, are more proliferative and less apoptotic compared with the wild-type (WT) CMPs. Finally, we observe that ANGPTL4 deficiency in macrophages promotes foam cell formation by enhancing CD36 expression and reducing ABCA1 localization in the cell surface. Altogether, these findings demonstrate that haematopoietic ANGPTL4 deficiency increases atherogenesis through regulating myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

  20. Intracellular trehalose improves the survival of human red blood cells by freeze-drying

    Institute of Scientific and Technical Information of China (English)

    HE Hui; LIU Baolin; HUA Zezhao; LI Chuan; WU Zhengzheng

    2007-01-01

    Freeze-drying of human red blood cells has a potential important application for blood transfusion.The aim of this study was to investigate the effects ofintracellular trehalose on the survival of red blood cells after freeze-drying and rehydration.Fresh red blood cells were incubated in trehalose solutions of various concentrations at 37℃ for 7 h following freeze-drying.Polyvinylpyrrolidone,Trehalose,sodium citrate,and human serum albumin were used as extracellular protective agents for the freeze-drying of red blood cells.The results indicated that the intracellular trehalose concentration was increased with increasing concentration of extracellular trehalose solution,and the maximum concen tration of intracellular trehalose reached 35 mmol/L.The viability of freeze-dried red blood cells increased with the increment of intracellular trehalose concentration.

  1. Characterization of Microvesicles Released from Human Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Duc Bach Nguyen

    2016-03-01

    Full Text Available Background/Aims: Extracellular vesicles (EVs are spherical fragments of cell membrane released from various cell types under physiological as well as pathological conditions. Based on their size and origin, EVs are classified as exosome, microvesicles (MVs and apoptotic bodies. Recently, the release of MVs from human red blood cells (RBCs under different conditions has been reported. MVs are released by outward budding and fission of the plasma membrane. However, the outward budding process itself, the release of MVs and the physical properties of these MVs have not been well investigated. The aim of this study is to investigate the formation process, isolation and characterization of MVs released from RBCs under conditions of stimulating Ca2+ uptake and activation of protein kinase C. Methods: Experiments were performed based on single cell fluorescence imaging, fluorescence activated cell sorter/flow cytometer (FACS, scanning electron microscopy (SEM, atomic force microscopy (AFM and dynamic light scattering (DLS. The released MVs were collected by differential centrifugation and characterized in both their size and zeta potential. Results: Treatment of RBCs with 4-bromo-A23187 (positive control, lysophosphatidic acid (LPA, or phorbol-12 myristate-13 acetate (PMA in the presence of 2 mM extracellular Ca2+ led to an alteration of cell volume and cell morphology. In stimulated RBCs, exposure of phosphatidylserine (PS and formation of MVs were observed by using annexin V-FITC. The shedding of MVs was also observed in the case of PMA treatment in the absence of Ca2+, especially under the transmitted bright field illumination. By using SEM, AFM and DLS the morphology and size of stimulated RBCs, MVs were characterized. The sizes of the two populations of MVs were 205.8 ± 51.4 nm and 125.6 ± 31.4 nm, respectively. Adhesion of stimulated RBCs and MVs was observed. The zeta potential of MVs was determined in the range from - 40 mV to - 10 m

  2. Phosphatidylserine exposure on stored red blood cells as a parameter for donor-dependent variation in product quality

    NARCIS (Netherlands)

    Dinkla, S.; Peppelman, M.; Raadt, J. van der; Atsma, F.; Novotny, V.M.J.; Kraaij, M.G.J. van; Joosten, I.; Bosman, G.J.C.G.M.

    2014-01-01

    BACKGROUND: Exposure of phosphatidylserine on the outside of red blood cells contributes to recognition and removal of old and damaged cells. The fraction of phosphatidylserine-exposing red blood cells varies between donors, and increases in red blood cell concentrates during storage. The susceptibi

  3. Study of neutral red interaction with DNA by resolution of rank deficient multi-way fluorescence data

    DEFF Research Database (Denmark)

    Moghaddam, Fatemeh Ghasemi; Kompany Zare, Mohsen; Gholami, Somayeh

    2012-01-01

    The interaction of neutral red (NR) as an efficient anticancer drug with DNA was studied under physiological pH condition. Three-way data array were recorded by measuring excitation-emission fluorescence during the titration of neutral red with DNA at constant pH. The acid-base equilibrium constant...

  4. Autophagic vesicles on mature human reticulocytes explain phosphatidylserine-positive red cells in sickle cell disease.

    Science.gov (United States)

    Mankelow, Tosti J; Griffiths, Rebecca E; Trompeter, Sara; Flatt, Joanna F; Cogan, Nicola M; Massey, Edwin J; Anstee, David J

    2015-10-08

    During maturation to an erythrocyte, a reticulocyte must eliminate any residual organelles and reduce its surface area and volume. Here we show this involves a novel process whereby large, intact, inside-out phosphatidylserine (PS)-exposed autophagic vesicles are extruded. Cell surface PS is a well-characterized apoptotic signal initiating phagocytosis. In peripheral blood from patients after splenectomy or in patients with sickle cell disease (SCD), the number of circulating red cells exposing PS on their surface is elevated. We show that in these patients PS is present on the cell surface of red cells in large (∼1.4 µm) discrete areas corresponding to autophagic vesicles. The autophagic vesicles found on reticulocytes are identical to those observed on red cells from splenectomized individuals and patients with SCD. Our data suggest the increased thrombotic risk associated with splenectomy, and patients with hemoglobinopathies is a possible consequence of increased levels of circulating mature reticulocytes expressing inside-out PS-exposed autophagic vesicles because of asplenia.

  5. Red blood cell transfusion in preterm neonates: current perspectives

    Directory of Open Access Journals (Sweden)

    Chirico G

    2014-06-01

    Full Text Available Gaetano ChiricoNeonatology and Neonatal Intensive Care Unit, Children Hospital, Spedali Civili, Brescia, ItalyAbstract: Preterm neonates, especially very low birth weight infants, remain a category of patients with high transfusion needs; about 90% of those with <1,000 g birth weight may be transfused several times during their hospital stay. However, neonatal red blood cells (RBC transfusion is not without risks. In addition to well-known adverse events, several severe side effects have been observed unique to preterm infants, such as transfusion-related acute gut injury, intraventricular hemorrhage, and increased mortality risk. It is therefore important to reduce the frequency of RBC transfusion in critically ill neonates, by delayed clamping or milking the umbilical cord, using residual cord blood for initial laboratory investigations, reducing phlebotomy losses, determining transfusion guidelines, and ensuring the most appropriate nutrition, with the optimal supplementation of iron, folic acid, and vitamins. Ideally, RBC transfusion should be tailored to the individual requirements of the single infant. However, many controversies still remain, and the decision on whether to transfuse or not is often made on an empirical basis. Recently, a few clinical trials have been performed with the aim to compare the risk/benefit ratio of restrictive versus liberal transfusion criteria. No significant differences in short-term outcomes were observed, suggesting that the restrictive criteria may reduce the need for transfusion and the related side effects. Neurodevelopmental long-term outcome seemed more favorable in the liberal group at first evaluation, especially for boys, and significantly better in the restrictive group at a later clinical investigation. Magnetic resonance imaging scans, performed at an average age of 12 years, showed that intracranial volume was substantially smaller in the liberal group compared with controls. When sex effects

  6. Iron deficiency in sickle cell anaemia patients in Dar es Salaam ...

    African Journals Online (AJOL)

    Iron deficiency in sickle cell anaemia patients in Dar es Salaam, Tanzania. ... Five milliliter of venous blood was taken from all children for serum Ferritin, serum ... of haemoglobin concentration did not significantly influence the body Iron status ...

  7. Theoretical models for near forward light scattering by a Plasmodium falciparum infected red blood cell

    Science.gov (United States)

    Sharma, S. K.

    2012-12-01

    A number of experimental elastic light scattering studies have been performed in the past few years with the aim of developing automated in vivo tools for differentiating a healthy red blood cell from a Plasmodium falciparum infected cell. This paper examines some theoretical aspects of the problem. An attempt has been made to simulate the scattering patterns of healthy as well as infected individual red blood cells. Two models, namely, a homogeneous sphere model and a coated sphere model have been considered. The scattering patterns predicted by these models are examined. A possible method for discriminating infected red blood cells from healthy ones has been suggested.

  8. Thioredoxin reductase deficiency potentiates oxidative stress, mitochondrial dysfunction and cell death in dopaminergic cells.

    Directory of Open Access Journals (Sweden)

    Pamela Lopert

    Full Text Available Mitochondria are considered major generators of cellular reactive oxygen species (ROS which are implicated in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD. We have recently shown that isolated mitochondria consume hydrogen peroxide (H₂O₂ in a substrate- and respiration-dependent manner predominantly via the thioredoxin/peroxiredoxin (Trx/Prx system. The goal of this study was to determine the role of Trx/Prx system in dopaminergic cell death. We asked if pharmacological and lentiviral inhibition of the Trx/Prx system sensitized dopaminergic cells to mitochondrial dysfunction, increased steady-state H₂O₂ levels and death in response to toxicants implicated in PD. Incubation of N27 dopaminergic cells or primary rat mesencephalic cultures with the Trx reductase (TrxR inhibitor auranofin in the presence of sub-toxic concentrations of parkinsonian toxicants paraquat; PQ or 6-hydroxydopamine; 6OHDA (for N27 cells resulted in a synergistic increase in H₂O₂ levels and subsequent cell death. shRNA targeting the mitochondrial thioredoxin reductase (TrxR2 in N27 cells confirmed the effects of pharmacological inhibition. A synergistic decrease in maximal and reserve respiratory capacity was observed in auranofin treated cells and TrxR2 deficient cells following incubation with PQ or 6OHDA. Additionally, TrxR2 deficient cells showed decreased basal mitochondrial oxygen consumption rates. These data demonstrate that inhibition of the mitochondrial Trx/Prx system sensitizes dopaminergic cells to mitochondrial dysfunction, increased steady-state H₂O₂, and cell death. Therefore, in addition to their role in the production of cellular H₂O₂ the mitochondrial Trx/Prx system serve as a major sink for cellular H₂O₂ and its disruption may contribute to dopaminergic pathology associated with PD.

  9. Elevated red blood cell distribution width is associated with intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Vural Yilmaz, Zehra; Gencosmanoglu Turkmen, Gulenay; Daglar, Korkut; Yılmaz, Elif; Kara, Ozgur; Uygur, Dilek

    2017-01-01

    Intrahepatic cholestasis of pregnancy is the most common pregnancy specific liver disease and related with adverse maternal and perinatal outcome. Red blood cell distribution width, an anisocytosis marker in a complete blood count, has been used as an inflammation marker in various diseases. However the association of red blood cell distribution width with intrahepatic cholestasis of pregnancy is unknown. We aimed to evaluate the relationship between red blood cell distribution width and intrahepatic cholestasis of pregnancy. Ninety pregnant women with intrahepatic cholestasis of pregnancy and ninety healthy pregnant women were included in the study. Their clinical and laboratory characteristics including red blood cell distribution width, liver function tests, fasting and postprandial bile acid concentrations were analyzed. Serum red blood cell distribution width cell levels were significantly higher in pregnants with intrahepatic cholestasis of pregnancy than healthy pregnants. We also demonstrated that red blood cell distribution Width levels were higher in severe disease than mild disease and was significantly correlated with fasting and postprandial bile acid concentration in intrahepatic cholestasis of pregnancy group. Our study showed that red blood cell distribution width, an easy and inexpensive marker; were associated with intrahepatic cholestasis of pregnancy and can be used as a diagnostic and prognostic marker in intrahepatic cholestasis of pregnancy.

  10. Perturbation of red blood cell membrane rigidity by extracellular ligands.

    Science.gov (United States)

    Paulitschke, M; Nash, G B; Anstee, D J; Tanner, M J; Gratzer, W B

    1995-07-01

    It is known that binding of extracellular antibodies against the major sialoglycoprotein, glycophorin A, reduced the deformability of the red blood cell membrane. This has been taken to result from new or altered interactions between the glycophorin A and the membrane skeleton. We have shown by means of the micropipette aspiration technique that antibodies against the preponderant transmembrane protein, band 3, induce similar effects. A definite but much smaller reduction in elasticity of the membrane is engendered by univalent Fab fragments of the anti-band 3 antibodies. By examining cells genetically devoid of glycophorin A or containing a variant of this constituent, truncated at the inner membrane surface, we have shown that the anti-band 3 antibodies do not act through the band 3-associated glycophorin A. We examined the effect of anti-glycophorin A antibodies on homozygous Wr(a+b-) cells, in which an amino acid replacement in band 3 annihilates the Wright b (Wrb) epitope (comprising sequence elements of glycophorin A and band 3) and thus, by implication disrupts or perturbs the band 3-glycophorin A interaction; these cells show a much smaller response to an anti-glycophorin A antibody than do normal controls. We infer that in this case anti-glycophorin A antibodies exert their rigidifying effect through the associated band 3. Another anti-glycophorin A antibody, directed against an epitope remote from the membrane surface, however, increases the rigidity of both Wr(a+b-) and normal cells. This implies that not all antibodies act in the same manner in modifying the membrane mechanical properties. The effect exerted by anti-band 3 antibodies appears not to be transmitted through the band 3-ankyrin-spectrin pathway because the rigidifying effect of the intact antibody persists at alkaline pH, at which there is evidence that the ankyrin-band 3 link is largely dissociated. The large difference between the effects of saturating concentrations of the divalent and

  11. Pharmacology of the human red cell voltage-dependent cation channel Part I. Activation by clotrimazole and analogues

    DEFF Research Database (Denmark)

    Barksmann, Trine Lyberth; Kristensen, Berit I.; Christophersen, Palle.

    2004-01-01

    Human red cells, Nonselective voltage dependent cation channel, NSVDC channel, Gárdos channel blockers, NSVDC channel activators......Human red cells, Nonselective voltage dependent cation channel, NSVDC channel, Gárdos channel blockers, NSVDC channel activators...

  12. Transfusion of leukocyte-depleted red blood cells is not a risk factor for nosocomial infections in critically ill children

    NARCIS (Netherlands)

    van der Wal, Judith; van Heerde, Marc; Markhorst, Dick G.; Kneyber, Martin C. J.

    Objectives: Transfusion of red blood cells is increasingly linked with adverse outcomes in critically ill children. We tested the hypothesis that leukocyte-depleted red blood cell transfusions were independently associated with increased development of bloodstream infections, ventilator-associated

  13. Amyloid β levels in human red blood cells.

    Directory of Open Access Journals (Sweden)

    Takehiro Kiko

    Full Text Available UNLABELLED: Amyloid β-peptide (Aβ is hypothesized to play a key role by oxidatively impairing the capacity of red blood cells (RBCs to deliver oxygen to the brain. These processes are implicated in the pathogenesis of Alzheimer's disease (AD. Although plasma Aβ has been investigated thoroughly, the presence and distribution of Aβ in human RBCs are still unclear. In this study, we quantitated Aβ40 and Aβ42 in human RBCs with ELISA assays, and provided evidence that significant amounts of Aβ could be detected in RBCs and that the RBC Aβ levels increased with aging. The RBC Aβ levels increased with aging. On the other hand, providing an antioxidant supplement (astaxanthin, a polar carotenoid to humans was found to decrease RBC Aβ as well as oxidative stress marker levels. These results suggest that plasma Aβ40 and Aβ42 bind to RBCs (possibly with aging, implying a pathogenic role of RBC Aβ. Moreover, the data indicate that RBC Aβ40 and Aβ42 may constitute biomarkers of AD. As a preventive strategy, therapeutic application of astaxanthin as an Aβ-lowering agent in RBCs could be considered as a possible anti-dementia agent. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN42483402.

  14. Human red blood cells deformed under thermal fluid flow.

    Science.gov (United States)

    Foo, Ji-Jinn; Chan, Vincent; Feng, Zhi-Qin; Liu, Kuo-Kang

    2006-03-01

    The flow-induced mechanical deformation of a human red blood cell (RBC) during thermal transition between room temperature and 42.0 degrees C is interrogated by laser tweezer experiments. Based on the experimental geometry of the deformed RBC, the surface stresses are determined with the aid of computational fluid dynamics simulation. It is found that the RBC is more deformable while heating through 37.0 degrees C to 42.0 degrees C, especially at a higher flow velocity due to a thermal-fluid effect. More importantly, the degree of RBC deformation is irreversible and becomes softer, and finally reaches a plateau (at a uniform flow velocity U > 60 microm s(-1)) after the heat treatment, which is similar to a strain-hardening dominated process. In addition, computational simulated stress is found to be dependent on the progression of thermotropic phase transition. Overall, the current study provides new insights into the highly coupled temperature and hydrodynamic effects on the biomechanical properties of human erythrocyte in a model hydrodynamic flow system.

  15. Perioperative Red Blood Cell Transfusion: What We Do Not Know

    Institute of Scientific and Technical Information of China (English)

    Chong Lei; Li-Ze Xiong

    2015-01-01

    Objective:Blood transfusion saves lives but may also increase the risk of injury.The objective of this review was to evaluate the possible adverse effects related to transfusion of red blood cell (RBC) concentrates stored for prolonged periods.Data Sources:The data used in this review were mainly from PubMed articles published in English up to February 2015.Study Selection:Clinical and basic research articles were selected according to their relevance to this topic.Results:The ex vivo changes to RBC that occur during storage are collectively called storage lesion.It is still inconclusive if transfusion of RBC with storage lesion has clinical relevance.Multiple ongoing prospective randomized controlled trials are aimed to clarify this clinical issue.It was observed that the adverse events related to stored RBC transfusion were prominent in certain patient populations,including trauma,critical care,pediatric,and cardiac surgery patients,which leads to the investigation of underlying mechanisms.It is demonstrated that free hemoglobin toxicity,decreasing of nitric oxide bioavailability,and free iron-induced increasing of inflammation may play an important role in this process.Conclusion:It is still unclear whether transfusion of older RBC has adverse effects,and if so,which factors determine such clinical effects.However,considering the magnitude of transfusion and the widespread medical significance,potential preventive strategies should be considered,especially for the susceptible recipients.

  16. Some technetium complexes for labelling red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Emery, M.F.

    1988-01-01

    A new approach to produce technetium labelled red blood cells, used routinely in diagnostic nuclear medicine, is reported. The enzyme Carbonic Anhydrase (CA), present in erythrocytes, is strongly inhibited by primary aromatic sulphonamides, which bind at the enzyme active site. Three types of ligand able to coordinate to technetium and suitable for modification to include a primary aromatic sulphonamide group were studied; bis(thiosemicarbazones), Schiff bases and some propylene amine oximes. The experimental conditions needed to label the ligands were determined. Both the thiosemicarbazone and propyleneamine oxime derivatives were labelled, but under no conditions attempted were the Schiff bases complexed by Technetium. The two major isozymes of Human Carbonic Anhydrase, HCA I and HCA II, were isolated from blood. The strength of binding of the free ligands SET, PN130 and PN135 with each of the isozymes was measured and expressed as the Dissociation Constant K{sub d}. The rate of uptake of the technetium complexes into washed RBCs and whole blood was measured and found to be much slower in whole blood. The biodistribution of both TcPN130 and TcPN135 in rats was determined and scintigraphic images for the TcPN130 complex were recorded. Attempts to synthesise the Tc-99 analogues on the milligram scale to allow chemical characterisation of these complexes were unsuccessful. (author).

  17. Characterization of Red Blood Cells with Multiwavelength Transmission Spectroscopy

    Directory of Open Access Journals (Sweden)

    Yulia M. Serebrennikova

    2015-01-01

    Full Text Available Multiwavelength transmission (MWT spectroscopy was applied to the investigation of the morphological parameters and composition of red blood cells (RBCs. The MWT spectra were quantitatively analyzed with a Mie theory based interpretation model modified to incorporate the effects of the nonsphericity and orientation of RBCs. The MWT spectra of the healthy and anemic samples were investigated for the RBC indices in open and blinded studies. When MWT performance was evaluated against a standard reference system, very good agreement between two methods, with R2>0.85 for all indices studied, was demonstrated. The RBC morphological parameters were used to characterize three types of anemia and to draw an association between RBC morphology and anemia severity. The MWT spectra of RBCs infected with malaria parasite Plasmodium falciparum at different life cycle stages were analyzed for RBC morphological parameters. The changes in the RBC volume, surface area, aspect ratio, and hemoglobin composition were used to trace the morphological and compositional alterations in the infected RBCs occurring with parasites’ development and to provide insights into parasite-host interactions. The MWT method was shown to be reliable for determination of the RBC morphological parameters and to be valuable for identification of the RBC pathologic changes and disease states.

  18. Aggregation of red blood cells in patients with Gaucher disease.

    Science.gov (United States)

    Adar, Tomer; Ben-Ami, Ronen; Elstein, Deborah; Zimran, Ari; Berliner, Shlomo; Yedgar, Saul; Barshtein, Gershon

    2006-08-01

    Gaucher disease is associated with increased red blood cell (RBC) aggregation, but the pathophysiological significance of this phenomenon and its correlation with disease manifestations are unclear. RBC aggregation was evaluated in 43 patients with Gaucher disease and 53 healthy controls. Dynamic RBC aggregation was examined in a narrow-gap flow chamber at varying shear stress. Compared with the controls, RBC aggregation in Gaucher disease was increased by 25%. Comparison of RBC aggregation in autologous plasma and in dextran (500 kDa) showed an increase both in plasma-dependent (extrinsic) and -independent (intrinsic) RBC aggregation. Subgroup analysis revealed that increased RBC aggregation was limited to patients with an intact spleen. RBC aggregation in patients did not correlate with plasma fibrinogen concentration, disease severity, enzyme replacement therapy or genotype. We conclude that RBC aggregation is increased in patients with Gaucher disease and an intact spleen, possibly reflecting the accumulation of glucocerebroside and other substances in the plasma and RBC membranes of these patients. Our results do not support a role for RBC aggregation in the pathogenesis of vascular complications of Gaucher disease.

  19. Zeroing in on red blood cell unit expiry.

    Science.gov (United States)

    Ayyalil, Fathima; Irwin, Greg; Ross, Bryony; Manolis, Michael; Enjeti, Anoop K

    2017-09-20

    Expiry of red blood cell (RBC) units is a significant contributor to wastage of precious voluntary donations. Effective strategies aimed at optimal resource utilization are required to minimize wastage. This retrospective study analyzed the strategic measures implemented to reduce expiry of RBC units in an Australian tertiary regional hospital. The measures, which included inventory rearrangement, effective stock rotation, and the number of emergency courier services required during a 24-month period, were evaluated. There was no wastage of RBC units due to expiry over the 12 months after policy changes. Before these changes, approximately half of RBC wastage (261/511) was due to expiry. The total number of transfusions remained constant in this period and there was no increase in the use of emergency couriers. Policy changes implemented were decreasing the RBC inventory level by one-third and effective stock rotation and using a computerized system to link the transfusion services across the area. Effective stock rotation resulted in a reduction in older blood (>28 days) received in the main laboratory rotated from peripheral hospitals, down from 6%-41% to 0%-2.5%. Age-related expiry of blood products is preventable and can be significantly reduced by improving practices in the pathology service. This study provides proof of principle for "zero tolerance for RBC unit expiry" across a large networked blood banking service. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  20. An innovative shape equation to quantify the morphological characteristics of parasitized red blood cells by Plasmodium falciparum and Plasmodium vivax.

    Science.gov (United States)

    Karimi, Alireza; Navidbakhsh, Mahdi; Motevalli Haghi, Afsaneh; Faghihi, Shahab

    2013-04-01

    The morphology of red blood cells is affected significantly during maturation of malaria parasites, Plasmodium falciparum and Plasmodium vivax. A novel shape equation is presented that defines shape of parasitized red blood cells by P. falciparum (Pf-red blood cells) and P. vivax (Pv-red blood cells) at four stages of infection. The Giemsa-stained thin blood films are prepared using blood samples collected from healthy donors, patients having P. falciparum and P. vivax malaria. The diameter and thickness of healthy red blood cells plus Pf-red blood cells and Pv-red blood cells at each stage of infection are measured from their optical images using Olysia and Scanning Probe Image Processor softwares, respectively. Using diameters and thicknesses of parasitized red blood cells, a shape equation is fitted and relative two-dimensional shapes are plotted using MATHEMATICA. The shape of Pf-red blood cell drastically changes at ring stage as its thickness increases by 82%, while Pv-red blood cell remains biconcave (30% increase in thickness). By trophozoite and subsequent schizont stage, the Pf-red blood cell entirely loses its biconcave shape and becomes near spherical (diameter and thickness of ~8 µm). The Pv-red blood cell remains biconcave throughout the parasite development even though its volume increases. These results could have practical use for faster diagnosis, prediction, and treatment of human malaria and sickle-cell diseases.

  1. Regulation of the viability of Nf1 deficient cells by PKC isoforms.

    Science.gov (United States)

    Zhou, Xiaodong; Shen, Ling; Parris, Toshima; Huang, Junchi; Yi, Bo; Helou, Khalil; Chen, Changyan

    2014-11-15

    Suppression of protein kinase C (PKC) is known to be synthetically lethal with ras mutations in various types of cancer cells. The studies also showed that blockade of PKC affected the viability of Nf1 deficient cells. Since PKC family consists of more than 10 isoforms, our study aimed at identifying which isoform(s) played the crucial role in sensitizing Nf1 deficient cells to apoptosis. Using genetic and chemical PKC inhibitors, we demonstrated that the concurrent inhibition of PKC α and β induced Nf1 deficient ST or 96.2 cells, but not SNF02.2 cells with a normal Nf1 or ST cells ectopically expressing Nf1 effective domain gene, to apoptosis. In this process, PKC δ in Nf1 deficient cells, but not in ST/Nf1 cells, was upregulated and translocated to the nucleus. Furthermore, caspase 3 was cleaved and cytochrome c was released to the cytosol. Thus, it appeared that PKC δ and α/β are the crucial components for sustaining the aberrant Ras signaling and further viability of Nf1 deficient cells. The abrogation of these two isoforms activated their opponent PKC δ for switching on the caspase 3-governed apoptotic machinery.

  2. Spiral Phyllotaxis Pattern in an Animal Cell: A Fluid- Driven Mechanism for Red Cell Echinocytosis and Programmed Cell Death

    OpenAIRE

    Lofthouse, J. T.

    2004-01-01

    This paper demonstrates that the pattern of lipid spiculesthat emerge on the surface of red blood cells in the classic 'Discocyte to Echinocyte' shape change is a generative spiral, and presents a qualitative, fluid- driven mechanism for their production, compatible with the work of Douady and Couder. Implications for the dynamics of cell growth, plant cell phyllotaxy, programmed cell death and gravity sensitivity are explained in terms of a new qualitative model of cellular fluid dynamics.

  3. Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

    OpenAIRE

    Stussi, G.; Halter, J; Bucheli, E; Valli, P V; Seebach, L; Gmür, J; Gratwohl, A; Passweg, J. R.; Seebach, J.D.

    2009-01-01

    BACKGROUND: Persistent anti-donor isoagglutinins after major ABO blood group incompatible hematopoietic stem cell transplantation may cause delayed red blood cell engraftment and post-transplant pure red cell aplasia. DESIGN AND METHODS: We investigated the effect of pretransplant anti-donor isoagglutinin reduction by in vivo absorption and/or plasmapheresis on the incidence of pure red cell aplasia and the time to red blood cell engraftment in 153 hematopoietic stem cell transplant recipient...

  4. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency

    Science.gov (United States)

    Boadi, J.; Sangwal, V.; MacNeil, S.; Matcher, S. J.

    2015-03-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells is continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. Limbal Stem Cell Deficiency (LSCD), in which the stem cell population is depleted, can lead to blindness. LSCD can be caused by chemical and thermal burns to the eye. A popular treatment, especially in emerging economies such as India, is the transplantation of limbal stem cells onto damaged limbus with hope of repopulating the region. Hence regenerating the corneal epithelium. In order to gain insights into the success rates of this treatment, new imaging technologies are needed in order to track the transplanted cells. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images of the retina. A custom OCT system has been built to image the corneal surface, to investigate the fate of transplanted limbal stem cells. We evaluate two methods to label and track transplanted cells: melanin labelling and magneto-labelling. To evaluate melanin labelling, stem cells are loaded with melanin and then transplanted onto a rabbit cornea denuded of its epithelium. The melanin displays strongly enhanced backscatter relative to normal cells. To evaluate magneto-labelling the stem cells are loaded with magnetic nanoparticles (20-30nm in size) and then imaged with a custom-built, magneto-motive OCT system.

  5. The mode of action of some antibiotics on red blood cell membranes.

    Science.gov (United States)

    Blaskó, K; Shagina, L V; Györgyi, S; Lev, A A

    1986-12-01

    Data are presented on the interaction of gramicidin, primycin and valinomycin with red blood cell membranes and compared with those obtained for artificial lipid bilayer membranes. The channel forming antibiotics gramicidin and primycin show specific kinetic behaviour in living cell membranes. It could be shown that the penetration of these antibiotics into the red blood cell membrane is a cooperative process resulting in the occurrence of aggregates in the lipid lattice of the membrane.

  6. Enhancement of heat transfer in red cell suspensions in vitro experiments.

    Science.gov (United States)

    Carr, R T; Tiruvaloor, N R

    1989-05-01

    New data on laminar heat convection with red cell suspensions have been gathered for both heating and cooling. When compared to data for the suspending medium alone, it is apparent that the red cells enhance laminar heat transfer when Pe greater than 4. This is probably due to particle movements. These new data disagree with earlier studies which indicated no enhancement of heat transfer for blood cell suspensions. The data do agree with previous correlations for enhanced thermal transport in sheared suspensions.

  7. Macromolecular depletion modulates the binding of red blood cells to activated endothelial cells.

    Science.gov (United States)

    Yang, Yang; Koo, Stephanie; Lin, Cheryl Shuyi; Neu, Björn

    2010-09-01

    Adhesion of red blood cells (RBCs) to endothelial cells (ECs) is usually insignificant but an enhanced adhesion has been observed in various diseases associated with vascular complications. This abnormal adhesion under pathological conditions such as sickle cell disease has been correlated with increased levels of various plasma proteins but the detailed underlying mechanism(s) remains unclear. Usually it is assumed that the proadhesive effects of plasma proteins originate from ligand interactions cross-linking receptors on adjacent cells, but explicit results detailing binding sites or receptors for some proteins (e.g., fibrinogen) on either RBC or EC surfaces that would support this model are missing. In this study, the authors tested whether there is an alternative mechanism. Their results demonstrate that dextran 2 MDa promotes the adhesion of normal RBCs to thrombin-activated ECs and that this effect becomes more pronounced with increasing thrombin concentration or with prolonged thrombin incubation time. It is concluded that depletion interaction originating from nonadsorbing macromolecules (i.e., dextran) can modulate the adhesion of red blood cells to thrombin-activated EC. This study thereby suggests macromolecular depletion as an alternative mechanism for the adhesion-promoting effects of nonadsorbing plasma proteins. These findings should not only aid in getting a better understanding of diseases associated with vascular complications but should also have many potential applications in biomedical or biotechnological areas that require the control of cell-cell or cell surface interactions.

  8. The Evaluation of Red Cell Distribution Width in Chronic Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Hikmet Tekce

    2014-01-01

    Full Text Available Background. Red cell distribution width (RDW has been used as a marker of iron deficiency; however, it is accepted as a marker of cardiovascular survival. We aimed to study RDW levels in hemodialysis (HD patients and the association between RDW and inflammatory, nutritional, and volume markers. Methods. We included 296 HD patients with sufficient iron storage and without anemia or hypervolemia. We grouped patients into four groups according to clinical parameters, albumin, and C-reactive protein (CRP. Results. The lowest RDW levels were found in group 1 (13.2%. Although RDW of group 2 was higher than that of group 1, it was still in normal range (14.7% versus 13.2%, P=0.028. RDW levels of groups 3 (17.8% and 4 (18.5% were significantly higher than those of groups 1 and 2 and above normal range. A positive correlation was detected between RDW and HD duration, interdialytic weight gain (IDWG, serum phosphate, and CRP levels and a negative correlation was detected with serum albumin. HD duration, CRP, IDWG, and serum albumin have been found as independent predictors of RDW elevation. Conclusions. Results of the present study reflect adverse effects of inflammation, malnutrition, and excess IDWG on RDW elevation in an HD study cohort with sufficient iron storage and without anemia and hypervolemia.

  9. TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Würts, S.Ø.; Rømer, Maria Unni Koefoed;

    2006-01-01

    in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate...... this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene...... deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells...

  10. Photodynamic effects of protoporphyrin on the architecture of erythrocyte membranes in protoporphyria and in normal red blood cells

    NARCIS (Netherlands)

    Goeij, A.F.P.M.; Vergaert, P.H.J.Th ver; Steveninck, J. van

    1975-01-01

    Protoporphyrin causes a photodynamic damage of the red blood cell membrane. After illumination of red blood cells in the presence of protoporphyrin three effects can be observed: 1. 1. Red blood cell membranes show particle aggregation on the outer and inner fracture face, as seen in freeze-etch e

  11. IFNγ producing CD8+ T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas

    OpenAIRE

    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie

    2015-01-01

    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8+ T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell s...

  12. Quantitative absorption cytometry for measuring red blood cell hemoglobin mass and volume.

    Science.gov (United States)

    Schonbrun, Ethan; Malka, Roy; Di Caprio, Giuseppe; Schaak, Diane; Higgins, John M

    2014-04-01

    We present an optical system, called the quantitative absorption cytometer (QAC), to measure the volume and hemoglobin mass of red blood cells flowing through a microfluidic channel. In contrast to clinical hematology analyzers, where cells are sphered in order for both volume and hemoglobin to be measured accurately, the QAC measures cells in their normal physiological shape. Human red blood cells are suspended in a refractive index-matching absorbing buffer, driven through a microfluidic channel, and imaged using a transmission light microscope onto a color camera. A red and a blue LED illuminate cells and images at each color are used to independently retrieve cell volume and hemoglobin mass. This system shows good agreement with red blood cell indices retrieved by a clinical hematology analyzer and in fact measures a smaller coefficient of variation of hemoglobin concentration. In addition to cell indices, the QAC returns height and mass maps of each measured cell. These quantitative images are valuable for analyzing the detailed morphology of individual cells as well as statistical outliers found in the data. We also measured red blood cells in hypertonic and hypotonic buffers to quantify the correlation between volume and hemoglobin mass under osmotic stress. Because this method is invariant to cell shape, even extremely nonspherical cells in hypertonic buffers can be measured accurately.

  13. Impaired precursor B cell differentiation in Bruton's tyrosine kinase-deficient mice

    NARCIS (Netherlands)

    S. Middendorp; G.M. Dingjan (Gemma); R.W. Hendriks (Rudi)

    2002-01-01

    textabstractBruton's tyrosine kinase (Btk) is a cytoplasmic signaling molecule that is crucial for precursor (pre-B) cell differentiation in humans. In this study, we show that during the transition of large cycling to small resting pre-B cells in the mouse, Btk-deficient cells fai

  14. Impaired precursor B cell differentiation in Bruton's tyrosine kinase-deficient mice

    NARCIS (Netherlands)

    S. Middendorp; G.M. Dingjan (Gemma); R.W. Hendriks (Rudi)

    2002-01-01

    textabstractBruton's tyrosine kinase (Btk) is a cytoplasmic signaling molecule that is crucial for precursor (pre-B) cell differentiation in humans. In this study, we show that during the transition of large cycling to small resting pre-B cells in the mouse, Btk-deficient cells

  15. Polyclonal Expansion of NKG2C+ NK Cells in TAP-deficient Patients

    Directory of Open Access Journals (Sweden)

    vivien eBeziat

    2015-10-01

    Full Text Available Adaptive natural killer (NK cell responses to human cytomegalovirus (CMV infection are characterized by the expansion of NKG2C+ NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs. Here, we set out to study the HLA class I-dependency of such NKG2C+ NK cell expansions. We demonstrate expansion of NKG2C+ NK cells in patients with transporter associated with antigen presentation (TAP-deficiency, whom express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C+ NK cell populations in TAP-deficient patients display a polyclonal KIR-profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR-repertoire of expanding NKG2C+ NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C+ NK cell expansions to occur. Thus, the emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to anti-viral immunity and potentially explain these patients’ low incidence of severe viral infections.

  16. Polyclonal Expansion of NKG2C+ NK Cells in TAP-Deficient Patients

    Science.gov (United States)

    Béziat, Vivien; Sleiman, Marwan; Goodridge, Jodie P.; Kaarbø, Mari; Liu, Lisa L.; Rollag, Halvor; Ljunggren, Hans-Gustaf; Zimmer, Jacques; Malmberg, Karl-Johan

    2015-01-01

    Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C+ NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C+ NK cell expansions. We demonstrate the expansion of NKG2C+ NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C+ NK cell populations in TAP-deficient patients display a polyclonal KIR profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR repertoire of expanding NKG2C+ NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C+ NK cell expansions to occur. The emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to antiviral immunity and potentially explain these patients’ low incidence of severe viral infections. PMID:26500647

  17. MLH1-deficient tumor cells are resistant to lipoplatin, but retain sensitivity to lipoxal.

    Science.gov (United States)

    Fedier, André; Poyet, Cédric; Perucchini, Daniele; Boulikas, Teni; Fink, Daniel

    2006-03-01

    Lipoplatin, currently under phase III evaluation, is a novel liposomal cisplatin formulation highly effective against cancers. Lipoplatin has eliminated or reduced the systemic toxicity frequently seen for cisplatin. The objective of the present study was to determine whether the cytotoxic effect of lipoplatin is dependent on the functional integrity of DNA mismatch repair (MMR), a post-replicative DNA repair machinery implicated in cell cycle control and apoptosis. Clonogenic data revealed a significant (Plipoplatin of HCT116 human colorectal adenocarcinoma cells lacking MLH1, one of five proteins crucial to MMR function, as compared to MLH1-expressing HCT116 cells. In addition, MLH1-deficient cells were at least 3-fold less susceptible to apoptosis (DNA fragmentation) than MLH1-proficient cells. However, proteolytic processing of caspase-3, caspase-7 and poly(ADP-ribose)polymerase-1 following lipoplatin treatment was comparable in MLH1-deficient cells and -proficient cells. Furthermore, MLH1-deficient cells retained the ability to attenuate cell cycle progression past the G2/M checkpoint following lipoplatin treatment. In conclusion, our results indicate that the lipoplatin-sensitive phenotype of MLH1-proficient cells correlated with increased apoptosis which may occur via caspase-independent pathways. They also suggest that the integrity of MMR function is a relevant determinant accounting for the cytotoxicity of lipoplatin. However, this does not seem to apply to lipoxal, a novel liposomal formulation of oxaliplatin, because MLH1-deficient cells were as sensitive to lipoxal as MLH1-proficient cells.

  18. Iron deficiency decreases hemolysis in sickle cell anemia Anemia ferropriva diminui hemólise em anemia falciforme

    Directory of Open Access Journals (Sweden)

    Oswaldo Castro

    2009-02-01

    Full Text Available A woman with homozygous sickle cell disease developed severe iron deficiency due to long-standing uterine bleeding. At this point, the serum lactic dehydrogenase level was normal and the reticulocyte count was only minimally elevated. This suggested that the low red cell hemoglobin concentration that resulted from iron deficiency also decreased Hb S polymerization and lowered the hemolytic rate. Iron replacement led first to a substantially improved hemoglobin concentration with only a minimal increase in the hemolytic rate and secondarily to a modest further improvement in the hemoglobin concentration and a marked increase in the hemolytic rate. The hematologic changes observed in this patient, and those in other iron deficient sickle cell patients reported in the literature, suggest that it may be appropriate to consider the induction of an intermediate iron deficient stage as experimental treatment in adult sickle cell patients.Uma mulher com anemia falciforme homozigose para a Hb S evoluiu com anemia ferropriva grave devido a sangramento uterino prolongado. A dosagem de dehidrogenase lática era normal e a contagem de reticulócitos estava levemente aumentada. Isto sugere que concentrações baixas de hemoglobina, que resulta de anemia ferropriva, também diminuem a polimeração de Hb S e reduz a taxa de hemólise. O complemento de ferro levou, primeiramente, a uma concentração substancialmente maior de hemoglobina com apenas um aumento mínimo na taxa hemolítica e subsequentemente a um aumento leve adicional na concentração da hemoglobina e um aumento notável na taxa hemolítica. As mudanças hematológicas observadas nesta paciente e aquelas em outras pacientes com anemia falciforme e também deficientes de ferro relatadas na literatura sugerem que pode ser interessante considerar a indução de deficiência de ferro como tratamento experimental em pacientes adultos com anemia falciforme.

  19. Ex-vivo expansion of red blood cells: how real for transfusion in humans?

    Science.gov (United States)

    Migliaccio, Anna Rita; Masselli, Elena; Varricchio, Lilian; Whitsett, Carolyn

    2012-03-01

    Blood transfusion is indispensable for modern medicine. In developed countries, the blood supply is adequate and safe but blood for alloimmunized patients is often unavailable. Concerns are increasing that donations may become inadequate in the future as the population ages prompting a search for alternative transfusion products. Improvements in culture conditions and proof-of-principle studies in animal models have suggested that ex-vivo expanded red cells may represent such a product. Compared to other cell therapies transfusion poses the unique challenge of requiring great cell doses (2.5×10(12) cells vs 10(7) cells). Although production of such cell numbers is theoretically possible, current technologies generate red cells in numbers sufficient only for safety studies. It is conceived that by the time these studies will be completed, technical barriers to mass cell production will have been eliminated making transfusion with ex-vivo generated red cells a reality.

  20. Tc-99m-labeled red blood cells for the measurement of red cell mass in newborn infants: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Linderkamp, O.; Betke, K.; Fendel, H.; Klemm, J.; Lorenzen, K.; Riegel, K.P.

    1980-07-01

    In vitro and in vivo investigations were performed to examine the binding of Tc-99m to neonatal red blood cells (RBC). Labeling efficiency was about 90%, and unbound Tc-99m less than 3% after one washing, in premature and full-term newborns and in children. Thus presence of high percentages of fetal hemoglobin (Hb F) did not influence the labeling of RBCs with Tc-99m. RBCs of 11 newborns were hemolysed and the distribution of Tc-99m on RBC components was analyzed. Although Hb F percentage averaged (60.0 +- 8.10)% (s.d.), only (11.9 +- 3.7)% of Tc-99m was bound by Hb F, whereas (45.0 +- 6.1)% was associated with Hb A. RBC membranes bound (13.7 +- 4.3)% and (29.3 +- 4.0)% were found unbound in hemolysates. These results indicate that Tc-99m preferentially binds to beta chains. In vivo equilibration of Tc-99m RBCs and of albumin labeled with Evans blue was investigated in five newborn infants. Tc-99m RBCs were stable in each case during the first hour after injection. Elution of Tc-99m from RBCs was (3.4 +- 1.5)% per h. Body-to-venous hematocrit ratio averaged 0.86 +- 0.03.

  1. Regulation of red blood cell deformability is independent of red blood cell-nitric oxide synthase under hypoxia.

    Science.gov (United States)

    Grau, Marijke; Lauten, Alexander; Hoeppener, Steffen; Goebel, Bjoern; Brenig, Julian; Jung, Christian; Bloch, Wilhelm; Suhr, Frank

    2016-09-12

    The aim was to study impacts of mild to severe hypoxia on human red blood cell (RBC)-nitric oxide synthase (NOS)-dependent NO production, protein S-nitrosylation and deformability.Ambient air oxygen concentration of 12 healthy subjects was step-wisely reduced from 20.95% to 16.21%, 12.35%, 10% and back to 20.95%. Additional in vitro experiments involved purging of blood (±sodium nitrite) with gas mixtures corresponding to in vivo intervention.Vital and hypoxia-associated parameters showed physiological adaptation to changing demands. Activation of RBC-NOS decreased with increasing hypoxia. RBC deformability, which is influenced by RBC-NOS activation, decreased under mild hypoxia, but surprisingly increased at severe hypoxia in vivo and in vitro. This was causatively induced by nitrite reduction to NO which increased S-nitrosylation of RBC α- and β-spectrins -a critical step to improve RBC deformability. The addition of sodium nitrite prevented decreases of RBC deformability under hypoxia by sustaining S-nitrosylation of spectrins suggesting compensatory mechanisms of non-RBC-NOS-produced NO.The results first time indicate a direct link between maintenance of RBC deformability under severe hypoxia by non-enzymatic NO production because RBC-NOS activation is reduced. These data improve our understanding of physiological mechanisms supporting adequate blood and, thus, oxygen supply to different tissues under severe hypoxia.

  2. Polymer/hemoglobin assemblies: biodegradable oxygen carriers for artificial red blood cells.

    Science.gov (United States)

    Li, Taihang; Jing, Xiabin; Huang, Yubin

    2011-07-07

    In routine clinical procedures, blood transfusion is now suffering from the defects of the blood products, like cross-matching, short storage time and virus infection. Various blood substitutes have been designed by researchers through continual efforts. With recent progress in nanotechnology, new types of artificial red blood cells with cellular structure are available. This article aims to describe some artificial red blood cells which encapsulate or conjugate hemoglobin molecules through various approaches, especially the nanoscale self-assembly technique, to mitigate the adverse effects of free hemoglobin molecules. These types of artificial red blood cell systems, which make use of biodegradable polymers as matrix materials, show advantages over the traditional types.

  3. Rheological properties of RBC in the microcirculation of mammalian skeletal muscle. [red blood cells

    Science.gov (United States)

    Ehrenberg, M. H.

    1974-01-01

    In the investigation the established technique of direct microscopic viewing was combined with the use of a closed circuit television system and cinematography. The red cell flow patterns in all capillaries were found to be oscillatory with characteristic cycle frequencies and amplitudes for all concentrations of inspired oxygen greater than 8%. Generally, there was a transient decrease in mean flow rate with increasing severity of hypoxia, with a gradual return toward control values. Red cell flow patterns are discussed along with questions of red cell configuration.

  4. Red blood cells transfusions in oncological patients treated with radio- and chemoterapy

    Directory of Open Access Journals (Sweden)

    Antić Ana

    2011-01-01

    Full Text Available Background/Aim. Anemia is one of the most frequent hematology disorders in patients with malignant diseases. It has a great influence on reduction of the quality of life, so it requires early diagnosis and an adequate treatment. The aim of this study was to present and analyze the treatment of anemia using red blood cell transfusions in patients with malignancies, to analyze adequate use of red blood cell transfusions according to hemoglobin concentration, and also the influence of the treatment of malignant disease on the level of anemia and use of red blood cells transfusion. Methods. This retrospective analysis included the data on the use of red blood cells in Oncological Clinic of Clinical Center Niš in a period from the 1st January 2008 to the 31st December 2008. Results. None of the patients received the whole blood. In this period, 735 patients received 1,006 units of red blood cells (red blood cell concentrate, resuspended, washed, filtered. An average use of red blood cell transfusion was 1.37 unit per oncological patient who received transfusion. The use of red blood cell units was adequate (87.60% of patients received transfusion of red cells when Hgb < 80 g/L. During radio- and chemotherapy we noticed a decrease of hematological parameter values. The patients of the experimental group were dependant on red blood cells transfusion. Statistically, a significant decrease of hemoglobin level was observed in patients treated only with radiotherapy who are the greatest consumers of red blood cells. Two patients were registered who more likely to have febrile nonhemolytic transfusion reactions. Posttransfusion alloimmunization occurred in 0.68% of the patients. Conclusion. The use of red blood cells in oncological patients is in compliance with the up to date tendencies and recommendations published in clinical guidelines. For the purpose of efficient transfusion support in patients with malignant diseases, we have to follow the newest

  5. Loss of Cell Adhesion Increases Tumorigenic Potential of Polarity Deficient Scribble Mutant Cells.

    Directory of Open Access Journals (Sweden)

    Indrayani Waghmare

    Full Text Available Epithelial polarity genes are important for maintaining tissue architecture, and regulating growth. The Drosophila neoplastic tumor suppressor gene scribble (scrib belongs to the basolateral polarity complex. Loss of scrib results in disruption of its growth regulatory functions, and downregulation or mislocalization of Scrib is correlated to tumor growth. Somatic scribble mutant cells (scrib- surrounded by wild-type cells undergo apoptosis, which can be prevented by introduction of secondary mutations that provide a growth advantage. Using genetic tools in Drosophila, we analyzed the phenotypic effects of loss of scrib in different growth promoting backgrounds. We investigated if a central mechanism that regulates cell adhesion governs the growth and invasive potential of scrib mutant cells. Here we show that increased proliferation, and survival abilities of scrib- cells in different genetic backgrounds affect their differentiation, and intercellular adhesion. Further, loss of scrib is sufficient to cause reduced cell survival, activation of the JNK pathway and a mild reduction of cell adhesion. Our data show that for scrib cells to induce aggressive tumor growth characterized by loss of differentiation, cell adhesion, increased proliferation and invasion, cooperative interactions that derail signaling pathways play an essential role in the mechanisms leading to tumorigenesis. Thus, our study provides new insights on the effects of loss of scrib and the modification of these effects via cooperative interactions that enhance the overall tumorigenic potential of scrib deficient cells.

  6. Safe extension of red blood cell storage life at 4{degree}C

    Energy Technology Data Exchange (ETDEWEB)

    Bitensky, M.; Yoshida, Tatsuro

    1996-04-01

    The project sought to develop methods to extend the storage life of red blood cells. Extended storage would allow donor to self or autologous transfusion, expand and stabilize the blood supply, reduce the cost of medical care and eliminate the risk of transfusion related infections, including a spectrum of hepatitides (A, B and C) and HIV. The putative cause of red blood cell spoilage at 4 C has been identified as oxidative membrane damage resulting from deoxyhemoglobin and its denaturation products including hemichrome, hemin and Fe{sup 3+}. Trials with carbon monoxide, which is a stabilizer of hemoglobin, have produced striking improvement of red blood cell diagnostics for cells stored at 4 C. Carbonmonoxy hemoglobin is readily converted to oxyhemoglobin by light in the presence of oxygen. These findings have generated a working model and an approach to identify the best protocols for optimal red cell storage and hemoglobin regeneration.

  7. Current topics in red cell biology: report on the Red Cell Special Interest Group meeting held at NHS Blood and Transplant Bristol on 30 October 2015.

    Science.gov (United States)

    Bullock, T; Bruce, L J; Ridgwell, K

    2016-08-01

    The Red Cell Special Interest Group (SIG) meeting, hosted by the British Blood Transfusion Society, provides an annual forum for the presentation of UK- and European-based red cell research. The 2015 meeting was held on Friday 30 October at the National Health Service Blood & Transplant (NHSBT) facility in Filton, Bristol and provided an exciting and varied programme on the themes of erythropoiesis, malaria biology and pathophysiology and red cells properties in stress and disease. Ten speakers presented on these topics over the course of one day. The meeting was well attended by over 90 delegates. Posters were presented during the lunch break, and abstracts from the posters are published at the end of this issue.

  8. Severe cutaneous human papilloma virus infection associated with Natural Killer cell deficiency following stem cell transplantation for severe combined immunodeficiency

    Science.gov (United States)

    Kamili, Qurat-ul-Ain; Seeborg, Filiz O; Saxena, Kapil; Nicholas, Sarah K; Banerjee, Pinaki P; Angelo, Laura S; Mace, Emily M; Forbes, Lisa R; Martinez, Caridad; Wright, Teresa S; Orange, Jordan S.; Hanson, Imelda Celine

    2016-01-01

    Capsule Summary The authors identify Natural Killer cell deficiency in post-transplant severe combined immunodeficiency patients who developed severe human papilloma virus infections as a long term complication. PMID:25159470

  9. Associations between red cell polymorphisms and Plasmodium falciparum infection in the middle belt of Ghana

    National Research Council Canada - National Science Library

    Amoako, Nicholas; Asante, Kwaku Poku; Adjei, George; Awandare, Gordon A; Bimi, Langbong; Owusu-Agyei, Seth

    2014-01-01

    .... In a cross-sectional study of 341 febrile children less than five years of age, associations between clinical malaria and common RBC polymorphisms including the sickle cell gene and G6PD deficiency...

  10. Double red cell concentrates -in vitro quality after delayed refrigeration.

    Science.gov (United States)

    Thomas, S; Bekoe, Y; Uddin, S; Beard, M; Cardigan, R

    2010-10-01

    Automated collection of red cell concentrates (RCC) presents a number of potential advantages to donors, blood services and recipients, and allows the collection of finished components from sites that are remote from a blood centre. However, data are lacking on how long the collected RCC may be stored at ambient temperature prior to their final storage at 4 °C. In this study, the Haemonetics Cymbal device was used to collect RCC using citrate, phosphate and dextrose (CPD-50) anticoagulant. A total of 10 procedures each yielded two leucodepleted RCC in saline, adenine, glucose and mannitol (SAGM) additive solution. One of each pair of RCC was kept warm in an insulated transport bag for 8 h and the other for 6 h. In vitro assessments of the quality of the RCC were made during subsequent 42-day storage of the RCC at 2-6 °C, and compared with reference data. All collected RCC were within UK and European limits for volume, haematocrit and haemoglobin content. Haemolysis was within specification at Day 42 and was no different in RCC held warm for 6 or 8 hours, but tended to be higher than reference data from whole blood derived RCC. ATP, 2,3 DPG and supernatant potassium levels were all similar in RCC held warm for 6 or 8 hours and reference data. We conclude that the Cymbal device may be used to collect two RCC in SAGM, and the in vitro assessment indicates that RCC may be stored without refrigeration for up to 8 h following collection, prior to final storage at 4 °C.

  11. Red cell properties after different modes of blood transportation

    Directory of Open Access Journals (Sweden)

    Asya Makhro

    2016-07-01

    Full Text Available Transportation of blood samples is unavoidable for assessment of specific parameters in blood of patients with rare anemias, blood doping testing or for research purposes. Despite the awareness that shipment may substantially alter multiple parameters, no study of that extend has been performed to assess these changes and optimize shipment conditions to reduce transportation-related artifacts. Here we investigate the changes in multiple parameters in blood of healthy donors over 72 hours of simulated shipment conditions. Three different anticoagulants (K3EDTA, Sodium Heparin and citrate-based CPDA for two temperatures (4oC and room temperature were tested to define the optimal transportation conditions. Parameters measured cover common cytology and biochemistry parameters (complete blood count, hematocrit, morphological examination, red blood cell (RBC volume, ion content and density, membrane properties and stability (hemolysis, osmotic fragility, membrane heat stability, patch-clamp investigations and formation of micro vesicles, Ca2+ handling, RBC metabolism, activity of numerous enzymes and O2 transport capacity. Our findings indicate that individual sets of parameter may require different shipment settings (anticoagulants, temperature. Most of the parameters except for ion (Na+, K+, Ca2+ handling and, possibly, reticulocytes counts, tend to favor transportation at 4oC. Whereas plasma and intraerythrocytic Ca2+ cannot be accurately measured in the presence of chelators such as citrate and EDTA, majority of Ca2+-dependent parameters are stabilized in CPDA samples. Even in blood samples from healthy donors transported using optimized shipment protocol the majority of parameters were stable within 24 hours, the condition that may not hold for the samples of patients with rare anemias. This implies for the as short as possible shipping using fast courier services to the closest expert laboratory at reach. Mobile laboratories or the travel of the

  12. Vesiculation of healthy and defective red blood cells

    Science.gov (United States)

    Li, He; Lykotrafitis, George

    2015-07-01

    Vesiculation of mature red blood cells (RBCs) contributes to removal of defective patches of the erythrocyte membrane. In blood disorders, which are related to defects in proteins of the RBC membrane, vesiculation of the plasma membrane is intensified. Several hypotheses have been proposed to explain RBC vesiculation but the exact underlying mechanisms and what determines the sizes of the vesicles are still not completely understood. In this work, we apply a two-component coarse-grained molecular dynamics RBC membrane model to study how RBC vesiculation is controlled by the membrane spontaneous curvature and by lateral compression of the membrane. Our simulation results show that the formation of small homogeneous vesicles with a diameter less than 40 nm can be attributed to a large spontaneous curvature of membrane domains. On the other hand, compression on the membrane can cause the formation of vesicles with heterogeneous composition and with sizes comparable with the size of the cytoskeleton corral. When spontaneous curvature and lateral compression are simultaneously considered, the compression on the membrane tends to facilitate formation of vesicles originating from curved membrane domains. We also simulate vesiculation of RBCs with membrane defects connected to hereditary elliptocytosis (HE) and to hereditary spherocytosis (HS). When the vertical connectivity between the lipid bilayer and the membrane skeleton is elevated, as in normal RBCs, multiple vesicles are shed from the compressed membrane with diameters similar to the cytoskeleton corral size. In HS RBCs, where the connectivity between the lipid bilayer and the cytoskeleton is reduced, larger-size vesicles are released under the same compression ratio as in normal RBCs. Lastly, we find that vesicles released from HE RBCs can contain cytoskeletal filaments due to fragmentation of the membrane skeleton while vesicles released from the HS RBCs are depleted of cytoskeletal filaments.

  13. Human and great ape red blood cells differ in plasmalogen levels and composition

    Directory of Open Access Journals (Sweden)

    Ely John J

    2011-06-01

    Full Text Available Abstract Background Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease. Results In a human and great ape cohort, we measured the red blood cell (RBC levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the sn-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the sn-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues. Conclusion We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and

  14. Induction of mitotic catastrophe by PKC inhibition in Nf1-deficient cells.

    Science.gov (United States)

    Zhou, Xiaodong; Kim, Sung-Hoon; Shen, Ling; Lee, Hyo-Jung; Chen, Changyan

    2014-01-01

    Mutations of tumor suppressor Nf1 gene deregulate Ras-mediated signaling, which confers the predisposition for developing benign or malignant tumors. Inhibition of protein kinase C (PKC) was shown to be in synergy with aberrant Ras for the induction of apoptosis in various types of cancer cells. However, it has not been investigated whether loss of PKC is lethal for Nf1-deficient cells. In this study, using HMG (3-hydroxy-3-methylgutaryl, a PKC inhibitor), we demonstrate that the inhibition of PKC by HMG treatment triggered a persistently mitotic arrest, resulting in the occurrence of mitotic catastrophe in Nf1-deficient ST8814 cells. However, the introduction of the Nf1 effective domain gene into ST8814 cells abolished this mitotic crisis. In addition, HMG injection significantly attenuated the growth of the xenografted ST8814 tumors. Moreover, Chk1 was phosphorylated, accompanied with the persistent increase of cyclin B1 expression in HMG-treated ST8814 cells. The knockdown of Chk1 by the siRNA prevented the Nf1-deficient cells from undergoing HMG-mediated mitotic arrest as well as mitotic catastrophe. Thus, our data suggested that the suppression of PKC activates the Chk1-mediated mitotic exit checkpoint in Nf1-deficient cells, leading to the induction of apoptosis via mitotic catastrophe. Collectively, the study indicates that targeting PKC may be a potential option for developing new strategies to treat Nf1-deficiency-related diseases.

  15. Prion Protein Deficiency Causes Diverse Proteome Shifts in Cell Models That Escape Detection in Brain Tissue.

    Science.gov (United States)

    Mehrabian, Mohadeseh; Brethour, Dylan; Williams, Declan; Wang, Hansen; Arnould, Hélène; Schneider, Benoit; Schmitt-Ulms, Gerold

    2016-01-01

    A popular method for studying the function of a given protein is to generate and characterize a suitable model deficient for its expression. For the prion protein (PrP), best known for its role in several invariably fatal neurodegenerative diseases, a natural choice, therefore, would be to undertake such studies with brain samples. We recently documented the surprising observation that PrP deficiency caused a loss or enhancement of NCAM1 polysialylation, dependent on the cell model used. To identify possible causes for this disparity, we set out to systematically investigate the consequence of PrP deficiency on the global proteome in brain tissue and in four distinct cell models. Here we report that PrP deficiency causes robust but surprisingly divergent changes to the global proteomes of cell models but has no discernible impact on the global brain proteome. Amongst >1,500 proteins whose levels were compared in wild-type and PrP-deficient models, members of the MARCKS protein family exhibited pronounced, yet cell model-dependent changes to their steady-state levels. Follow-up experiments revealed that PrP collaborates with members of the MARCKS protein family in its control of NCAM1 polysialylation. We conclude that the physiological function of PrP may be masked in analyses of complex brain samples but its cell-type specific influence on a lipid raft-based NCAM1-related cell biology comes to the fore in investigations of specific cell types.

  16. Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Johansen, J; Marker, O

    1996-01-01

    To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually...... this phenomenon could reflect participation of B cells and/or Abs in long term virus control, similar experiments were performed with mice that do not have mature B cells because of a disrupted membrane exon of the mu chain gene. In these mice, the cell-mediated immune response was slightly delayed, but transient...... and that in their absence, the virus-specific CTL potential becomes exhausted. Together our results indicate that while CD8+ cells play a dominant role in acute virus control, all three major components of the immune system are required for long term virus control....

  17. Flow structures and red blood cell dynamics in arteriole of dilated or constricted cross section.

    Science.gov (United States)

    Gambaruto, Alberto M

    2016-07-26

    Vessel with 'circular' or 'star-shaped' cross sections are studied, representing respectively dilated or constricted cases where endothelial cells smoothly line or bulge into the lumen. Computational haemodynamics simulations are carried out on idealised periodic arteriole-sized vessels, with red blood cell 'tube' hematocrit value=24%. A further simulation of a single red blood cell serves for comparison purposes. The bulk motion of the red blood cells reproduces well-known effects, including the presence of a cell-free layer and the apparent shear-thinning non-Newtonian rheology. The velocity flow field is analysed in a Lagrangian reference frame, relative to any given red blood cell, hence removing the bulk coaxial motion and highlighting instead the complex secondary flow patterns. An aggregate formation becomes apparent, continuously rearranging and dynamic, brought about by the inter-cellular fluid mechanics interactions and the deformability properties of the cells. The secondary flow field induces a vacillating radial migration of the red blood cells. At different radial locations, the red blood cells express different residence times, orientation and shape. The shear stresses exerted by the flow on the vessel wall are influenced by the motion of red blood cells, despite the presence of the cell-free layer. Spatial (and temporal) variations of wall shear stress patters are observed, especially for the 'circular' vessel. The 'star-shaped' vessel bears considerable stress at the protruding endothelial cell crests, where the stress vectors are coaxially aligned. The bulging endothelial cells hence regularise the transmission of stresses on the vessel wall.

  18. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations

    Science.gov (United States)

    Qian, Bingjun; Shen, Shanqi; Zhang, Jianhua

    2017-01-01

    The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

  19. Red blood cells from induced pluripotent stem cells: hurdles and developments.

    Science.gov (United States)

    Mazurier, Christelle; Douay, Luc; Lapillonne, Hélène

    2011-07-01

    In the context of chronic blood supply difficulties, generating cultured red blood cells (cRBCs) in vitro after amplification of stem cells makes sense. This review will focus on the recent findings about the generation of erythroid cells from induced pluripotent stem (iPS) cells and deals with the hurdles and next developments that will occur. The most proliferative source of stem cells for generating cRBCs is the cord blood, but this source is limited in terms of hematopoietic stem cells and dependent on donations. Pluripotent stem cells are thus the best candidates and potential sources of cRBCs. Critical advances have led towards the in-vitro production of functional RBCs from iPS cells in the last few years. Because iPS cells can proliferate indefinitely and can be selected for a phenotype of interest, they are potential candidates to organize complementary sources of RBCs for transfusion. Proof of concept of generating cRBCs from iPS cells has been performed, but the procedures need to be optimized to lead to clinical application in blood transfusion. Several crucial points remain to be resolved. Notably these include the choice of the initial cell type to generate iPS cells, the method of reprogramming, that is, to ensure the safety of iPS cells as clinical grade, the optimization of erythrocyte differentiation, and the definition of good manufacturing practice (GMP) conditions for industrial production.

  20. Proteomic analysis identifies differentially expressed proteins after red propolis treatment in Hep-2 cells.

    Science.gov (United States)

    Frozza, Caroline Olivieri da Silva; Ribeiro, Tanara da Silva; Gambato, Gabriela; Menti, Caroline; Moura, Sidnei; Pinto, Paulo Marcos; Staats, Charley Christian; Padilha, Francine Ferreira; Begnini, Karine Rech; de Leon, Priscila Marques Moura; Borsuk, Sibele; Savegnago, Lucielli; Dellagostin, Odir; Collares, Tiago; Seixas, Fabiana Kömmling; Henriques, João Antonio Pêgas; Roesch-Ely, Mariana

    2014-01-01

    Here we investigated alterations in the protein profile of Hep-2 treated with red propolis using two-dimensional electrophoresis associated to mass spectrometry and apoptotic rates of cells treated with and without red propolis extracts through TUNEL and Annexin-V assays. A total of 325 spots were manually excised from the two-dimensional gel electrophoresis and 177 proteins were identified using LC-MS-MS. Among all proteins identified that presented differential expression, most were down-regulated in presence of red propolis extract at a concentration of 120 μg/mL (IC50): GRP78, PRDX2, LDHB, VIM and TUBA1A. Only two up-regulated proteins were identified in this study in the non-cytotoxic (6 μg/mL) red propolis treated group: RPLP0 and RAD23B. TUNEL staining assay showed a markedly increase in the mid- to late-stage apoptosis of Hep-2 cells induced by red propolis at concentrations of 60 and 120 μg/mL when compared with non-treated cells. The increase of late apoptosis was confirmed by in situ Annexin-V analysis in which red propolis extract induced late apoptosis in a dose-dependent manner. The differences in tumor cell protein profiles warrant further investigations including isolation of major bioactive compounds of red propolis in different cell lines using proteomics and molecular tests to validate the protein expression here observed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Ccr5 deficiency regulates the proliferation and trafficking of natural killer cells under physiological conditions.

    Science.gov (United States)

    Weiss, Ido D; Shoham, Hadas; Wald, Ori; Wald, Hanna; Beider, Katia; Abraham, Michal; Barashi, Neta; Galun, Eithan; Nagler, Arnon; Peled, Amnon

    2011-06-01

    Chemokines were shown to govern the trafficking of immune cells and may also play important roles in the survival and activation of these cells. We report here that under physiological conditions, the bone marrow (BM), spleen, blood and liver of Ccr5, but not of Ccr1-deficient mice, contain reduced numbers of NK cells. NK cells in the BM of Ccr5-deficient mice proliferate to a lesser extent compared to WT mice. Furthermore, spleen NK cells derived from Ccr5-deficient mice that were transplanted into irradiated recipients failed to proliferate in the host. Ccr5, but not Ccr1-deficient NK cells, failed to migrate in vitro in response to RANTES and MIP-1β but not MIP-1β or SDF-1 and had reduced activation, lower expression levels of NK cell markers and a slightly reduced capacity to adhere to target cells and stimulate their killing. Using the polyI:C mouse model for NK trafficking, we found that in the absence of Ccr5, but not Ccr1, NK cells failed to accumulate in the liver. In contrast, using the influenza viral infection as a model to evaluate NK cell proliferation, we found that Ccr5-deficient NK cells in the BM had a higher proliferation rate than WT NK cells. These results suggest a role for Ccr5 in NK cell proliferation and circulation under physiological conditions and a complex role for Ccr5 in determining the fate of NK cells under pathological conditions. Copyright © 2011. Published by Elsevier Ltd.

  2. From artificial red blood cells, oxygen carriers, and oxygen therapeutics to artificial cells, nanomedicine, and beyond.

    Science.gov (United States)

    Chang, Thomas M S

    2012-06-01

    The first experimental artificial red blood cells have all three major functions of red blood cells (rbc). However, the first practical one is a simple polyhemoglobin (PolyHb) that only has an oxygen-carrying function. This is now in routine clinical use in South Africa and Russia. An oxygen carrier with antioxidant functions, PolyHb-catalase-superoxide dismutase, can fulfill two of the three functions of rbc. Even more complete is one with all three functions of rbc in the form of PolyHb-catalase-superoxide dismutase-carbonic anhydrase. The most advanced ones are nanodimension artificial rbc with either PEG-lipid membrane or PEG-PLA polymer membrane. Extensions into oxygen therapeutics include a PolyHb-tyrosinase that suppresses the growth of melanoma in a mice model. Another is a PolyHb-fibrinogen that is an oxygen carrier with platelet-like function. Research has now extended well beyond the original research on artificial rbc into many areas of artificial cells. These include nanoparticles, nanotubules, lipid vesicles, liposomes, polymer-tethered lipid vesicles, polymersomes, microcapsules, bioencapsulation, nanocapules, macroencapsulation, synthetic cells, and others. These are being used in nanotechnology, nanomedicine, regenerative medicine, enzyme/gene therapy, cell/stem cell therapy, biotechnology, drug delivery, hemoperfusion, nanosensers, and even by some groups in agriculture, industry, aquatic culture, nanocomputers, and nanorobotics.

  3. [Production of mature red blood cell by using peripheral blood mononuclear cells].

    Science.gov (United States)

    Jia, Yan-Jun; Liu, Jiang; Zhang, Ke-Ying; Shang, Xiao-Yan; Li, Wei; Wang, Li-Jun; Liu, Na; Wang, Lin; Cui, Shuang; Ni, Lei; Zhao, Bo-Tao; Wang, Dong-Mei; Gao, Song-Ming; Zhang, Zhi-Xin

    2014-10-01

    Most protocols for in vitro producing red blood cells (RBC) use the CD34(+) cells or embryonic stem cells from cord blood, bone marrow or peripheral blood as the start materials. This study was purposed to produce the mature RBC in vitro by using peripheral blood mononuclear cells as start material. The peripheral blood mononuclear cells (PBMNC) were isolated from buffy coat after blood leukapheresis, the mature red blood cells (RBC) were prepared by a 4-step culture protocol. The results showed that after culture by inducing with the different sets of cytokines and supporting by mouse MS-5 cell line, the expansion of PBMNC reached about 1000 folds at the end of the culture. About 90% of cultured RBC were enucleated mature cells which had the comparable morphological characteristics with normal RBC. Colony-forming assays showed that this culture system could stimulate the proliferation of progenitors in PBMNC and differentiate into erythroid cells. The structure and function analysis indicated that the mean cell volume of in vitro cultured RBC was 118 ± 4 fl, which was slight larger than that of normal RBC (80-100 fl); the mean cell hemoglobin was 36 ± 1.2 pg, which was slight higher than that of normal RBC (27-31 pg); the maximal deformation index was 0.46, which approachs level of normal RBC; the glucose-6-phosphate dehydrogenase and pyrurvate kinase levels was consistant with young RBC. It is concluded that PBMNC are feasble, convenient and low-cost source for producing cultured RBC and this culture system is suitable to generate the RBC from PBMNC.

  4. Biosignatures of Kerala red rain cells: Implications in understanding their origin

    Science.gov (United States)

    Gangappa, R.; Thomas, M.; Hogg, S.

    2013-09-01

    The red rain that fell over Kerala, southern India (2001-2012) was characterised by the red pigmented particles. Earlier proposal claiming that these are known algal bloom blown from trees (Sampath et al, 2001; DiGregorio, 2007) has been studied by us and disproved. Also, further investigation reporting their extraordinary properties including a suggestion that they lack DNA (Louis and Kumar 2003; 2006; 2008) has been invalidated (Gangappa and Hogg, 2013). However, their claim regarding the growth and replication of these cells at 300ºC needs more investigation if it is to gain acceptance. Current study provide evidences regarding the biological properties of Kerala red rain cells to gain insights into environmental conditions from which they may have originated. Combined with various research strategies and high resolution instruments, we have demonstrated the following interesting properties of Kerala red rain cells: (1) unusually thick external envelope enclosing the central core; (2)stability of red pigment at temperatures about 100ºC and pH variations; (3) absence of eukaryotic ultrastructures; (4) possible replication at 121ºC with nanostructures (possible daughter cells) having similar morphological features inside the large mother cells at such high temperature. They contain high percentage of carbon, iron, silicon and aluminum and often enclosed in a silicon rich biofilms. Further investigation shows that the positive detection of DNA in these cells was possible only after the complete removal of red pigment, thereby providing an explanation for the negative outcome of earlier studies in this regard. Moreover, evidences are shown to support that these cells contain high amounts of UV absorbing compounds, porphyrin complexes and possible scytonemin. Kerala red rain cells may prove to be polyextermophiles belonging to prokaryotes and may have possibly originated from the environment containing above mentioned chemical elements, high energy UV exposure and

  5. Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.

    Science.gov (United States)

    Baker, Gregory J; Chockley, Peter; Yadav, Viveka Nand; Doherty, Robert; Ritt, Michael; Sivaramakrishnan, Sivaraj; Castro, Maria G; Lowenstein, Pedro R

    2014-09-15

    Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1-deficient glioma cells could be eradicated by host NK cells before the initiation of an antitumor T-cell response. In vitro experiments demonstrated that galectin-1-deficient GL26-Cit glioma cells are ∼3-fold more sensitive to NK-mediated tumor lysis than galectin-1-expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells. Cancer Res; 74(18); 5079-90. ©2014 AACR. ©2014 American Association for Cancer Research.

  6. Influence of laser and LED irradiation on mast cells of cutaneous wounds of rats with iron deficiency anemia

    Science.gov (United States)

    Becher Rosa, Cristiane; Oliveira Sampaio, Susana C. P.; Monteiro, Juliana S. C.; Ferreira, Maria F. L.; Zanini, Fátima A. A.; Santos, Jean N.; Cangussú, Maria Cristina T.; Pinheiro, Antonio L. B.

    2011-03-01

    This work aimed to study histologically the effect of Laser or LED phototherapy on mast cells on cutaneous wounds of rats with iron deficiency. 18 rats were used and fed with special peleted iron-free diet. An excisional wound was created on the dorsum of each animal which were divided into: Group I - Control with anemia + no treatment; Group II - Anemia + Laser; Group III - Anemia + LED; Group IV - Healthy + no treatment; Group V - Healthy + Laser; Group VI - Healthy + LED. Irradiation was performed using a diode Laser (λ660nm, 40mW, CW, total dose of 10J/cm2, 4X2.5J/cm2) or a RED-LED ( λ700nm, 15mW, CW, total dose of 10J/cm2). Histological specimens were routinely processed, cut and stained with toluidine blue and mast cell counts performed. No significant statistic difference was found between groups as to the number of degranulated, non-degradulated or total mast cells. Greater mean values were found for degranulated mast cells in the Anemia + LED. LED irradiation on healthy specimens resulted in a smaller number of degranulated mast cells. Our results leads to conclude that there are no significant differences in the number of mast cells seven days after irradiation following Laser or LED phototherapy.

  7. B7-deficient autoreactive T cells are highly susceptible to suppression by CD4(+)CD25(+) regulatory T cells.

    Science.gov (United States)

    May, Kenneth F; Chang, Xing; Zhang, Huiming; Lute, Kenneth D; Zhou, Penghui; Kocak, Ergun; Zheng, Pan; Liu, Yang

    2007-02-01

    CD4(+)CD25(+) regulatory T cells (Tregs) suppress immunity to infections and tumors as well as autoimmunity and graft-vs-host disease. Since Tregs constitutively express CTLA-4 and activated T cells express B7-1 and B7-2, it has been suggested that the interaction between CTLA-4 on Tregs and B7-1/2 on the effector T cells may be required for immune suppression. In this study, we report that autopathogenic T cells from B7-deficient mice cause multiorgan inflammation when adoptively transferred into syngeneic RAG-1-deficient hosts. More importantly, this inflammation is suppressed by adoptive transfer of purified wild-type (WT) CD4(+)CD25(+) T cells. WT Tregs also inhibited lymphoproliferation and acquisition of activation markers by the B7-deficient T cells. An in vitro suppressor assay revealed that WT and B7-deficient T cells are equally susceptible to WT Treg regulation. These results demonstrate that B7-deficient T cells are highly susceptible to immune suppression by WT Tregs and refute the hypothesis that B7-CTLA-4 interaction between effector T cells and Tregs plays an essential role in Treg function.

  8. A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells

    Science.gov (United States)

    Noble, Philip W.; Young, Melissa R.; Bernatsky, Sasha; Weisbart, Richard H.; Hansen, James E.

    2014-01-01

    Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A subset of lupus autoantibodies is associated with nucleolytic activity, and some of these antibodies are capable of nuclear penetration. We hypothesized that such antibodies might have potential as therapeutic agents targeted towards DNA repair-deficient malignancies. We identified the lupus autoantibody 5C6 as a cell-penetrating nucleolytic antibody and found that 5C6 has a differential effect on a matched pair of BRCA2-proficient and deficient DLD1 colon cancer cells. 5C6 selectively induced γH2AX in, and suppressed the growth of, the BRCA2-deficient cells. These findings demonstrate the potential utility of 5C6 in targeted therapy for DNA repair-deficient malignancies and strengthen the rationale for studies of additional lupus autoantibodies in order to identify the best candidates for development as therapeutic agents. In addition, the toxic effect of 5C6 on BRCA2-deficient cells provides further support for the hypothesis that some lupus autoantibodies contribute to the lower risk of specific cancers associated with systemic lupus erythematosus. PMID:25091037

  9. Current issues relating to the transfusion of stored red blood cells.

    Science.gov (United States)

    Zimrin, A B; Hess, J R

    2009-02-01

    The development of blood storage systems allowed donation and transfusion to be separated in time and space. This separation has permitted the regionalization of donor services with subsequent economies of scale and improvements in the quality and availability of blood products. However, the availability of storage raises the question of how long blood products can and should be stored and how long they are safe and effective. The efficacy of red blood cells was originally measured as the increment in haematocrit and safety began with typing and the effort to reduce the risk of bacterial contamination. Appreciation of a growing list of storage lesions of red blood cells has developed with our increasing understanding of red blood cell physiology and our experience with red blood cell transfusion. However, other than frank haemolysis, rare episodes of bacterial contamination and overgrowth, the reduction of oxygen-carrying capacity associated with the failure of some transfused cells to circulate, and the toxicity of lysophospholipids released from membrane breakdown, storage-induced lesions have not had obvious correlations with safety or efficacy. The safety of red blood cell storage has also been approached in retrospective epidemiologic studies of transfused patients, but the results are frequently biased by the fact that sicker patients are transfused more often and blood banks do not issue blood products in a random order. Several large prospective studies of the safety of stored red blood cells are planned.

  10. Extending the Clinical Phenotype of Adenosine Deaminase 2 Deficiency.

    Science.gov (United States)

    Ben-Ami, Tal; Revel-Vilk, Shoshana; Brooks, Rebecca; Shaag, Avraham; Hershfield, Michael S; Kelly, Susan J; Ganson, Nancy J; Kfir-Erenfeld, Shlomit; Weintraub, Michael; Elpeleg, Orly; Berkun, Yackov; Stepensky, Polina

    2016-10-01

    Adenosine deaminase 2 deficiency is an autoinflammatory disease, characterized by various forms of vasculitis. We describe 5 patients with adenosine deaminase 2 deficiency with various hematologic manifestations, including pure red cell aplasia, with no evidence for vasculitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Recurrent thymoma with stiff-person syndrome and pure red blood cell aplasia.

    Science.gov (United States)

    Kobayashi, Rei; Kaji, Masahiro; Horiuchi, Sho; Miyahara, Naofumi; Hino, Yumi; Suemasu, Keiichi

    2014-05-01

    Stiff-person syndrome (formerly known as stiff-man syndrome) is a very rare autoimmune and neurogenic disorder, thought to present as a paraneoplastic variant in association with thymoma. Pure red blood cell aplasia is also a paraneoplastic disorder associated with thymoma. Although separate cases of stiff-person syndrome and pure red blood cell aplasia have been reported, we describe here what is to our knowledge the first case of recurrent thymoma with both stiff-person syndrome and pure red blood cell aplasia. We describe the successful treatment of the neurogenic symptoms of stiff-person syndrome and the progressive anemia associated with pure red blood cell aplasia by tumor excision.

  12. Red cell concentrates of hemochromatosis patients comply with the storage guidelines for transfusion purposes.

    NARCIS (Netherlands)

    Luten, M.; Roerdinkholder-Stoelwinder, B.; Rombout-Sestrienkova, E.; Grip, W.J. de; Bos, H.J.; Bosman, G.J.C.G.M.

    2008-01-01

    BACKGROUND: Therapeutic phlebotomy is the preferred treatment for iron overload associated with hemochromatosis. In the Netherlands, red blood cell concentrates (RCCs) from hemochromatosis patients are not used for transfusion purposes. In this study, their storage performance was compared with that

  13. Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute

    National Research Council Canada - National Science Library

    Haruki, Risa; Kimura, Takuya; Iwasaki, Hitomi; Yamada, Kana; Kamiyama, Ikuo; Kohno, Mitsutomo; Taguchi, Kazuaki; Nagao, Saori; Maruyama, Toru; Otagiri, Masaki; Komatsu, Teruyuki

    2015-01-01

    A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell structured hemoglobin-albumin cluster designated as "HemoAct", is an O2-carrier designed for use as a red blood cell (RBC) substitute...

  14. Red cell concentrates of hemochromatosis patients comply with the storage guidelines for transfusion purposes.

    NARCIS (Netherlands)

    Luten, M.; Roerdinkholder-Stoelwinder, B.; Rombout-Sestrienkova, E.; Grip, W.J. de; Bos, H.J.; Bosman, G.J.C.G.M.

    2008-01-01

    BACKGROUND: Therapeutic phlebotomy is the preferred treatment for iron overload associated with hemochromatosis. In the Netherlands, red blood cell concentrates (RCCs) from hemochromatosis patients are not used for transfusion purposes. In this study, their storage performance was compared with that

  15. Isolation of a Kell-reactive protein from red cell membranes.

    Science.gov (United States)

    Wallas, C; Simon, R; Sharpe, M A; Byler, C

    1986-01-01

    A red cell membrane protein which exhibits Kell blood group antigen activity has been identified with a purified anti-Kell bound to a Protein-A agarose column and eluting with lithium diiodosalicylate (LIS). Although anti-Kell as well as the Kell-reactive membrane protein were eluted from the column, the eluate was capable of reducing the titer of added anti-Kell from 64 to 4. In addition, the eluate was shown to possess Kell reactivity by binding I125 Protein A after incubation with anti-Kell. Electrophoresis (SDS gel polyacrylamide 5-20% gradient) showed a band at approximately 90,000 daltons when solubilized membranes from Kell-positive red cells were used but not when membranes from dithiothreitol- and papain-treated Kell-positive red cells or Kell-negative red cells were used. A band isolated with unreduced conditions was capable of neutralizing anti-Kell.

  16. Acute iatrogenic polycythemia induced by massive red blood cell transfusion during subtotal abdominal colectomy

    Directory of Open Access Journals (Sweden)

    David Chiapaikeo

    2015-03-01

    Full Text Available A 46 year old man was transfused ten units of packed red blood cells during subtotal colectomy after intraoperative point-of-care testing values demonstrated hemoglobin values less than seven grams per deciliter (g/dL. A post-operative hemoglobin analyzed in a standard hematologic laboratory revealed a hemoglobin value of 27.8 g/dL. He underwent emergent red blood cell depletion therapy which decreased his hemoglobin to 7.5 g/dL. The physiologic consequences of iatrogenic polycythemia caused by massive transfusion during major abdominal surgery must take into account the fluid shifts that interplay between the osmotic load, viscosity of blood, and postoperative third spacing of fluid. Treatment of acute iatrogenic polycythemia can be effectively accomplished by red blood cell depletion therapy. However, fluid shifts caused by massive transfusion followed by rapid red cell depletion produce a unique physiologic state that is without a well-described algorithm for management.

  17. Generation of red blood cells from human embryonic/induced pluripotent stem cells for blood transfusion.

    Science.gov (United States)

    Ebihara, Yasuhiro; Ma, Feng; Tsuji, Kohichiro

    2012-06-01

    Red blood cell (RBC) transfusion is necessary for many patients with emergency or hematological disorders. However, to date the supply of RBCs remains labile and dependent on voluntary donations. In addition, the transmission of infectious disease via blood transfusion from unspecified donors remains a risk. Establishing a large quantity of safe RBCs would help to address this issue. Human embryonic stem (hES) cells and the recently established human induced pluripotent stem (hiPS) cells represent potentially unlimited sources of donor-free RBCs for blood transfusion, as they can proliferate indefinitely in vitro. Extensive research has been done to efficiently generate transfusable RBCs from hES/iPS cells. Nevertheless, a number of challenges must be overcome before the clinical usage of hES/iPS cell-derived RBCs can become a reality.

  18. Impression cytology and in vivo confocal microscopy in corneas with total limbal stem cell deficiency

    Directory of Open Access Journals (Sweden)

    Aline Lütz de Araújo

    2013-10-01

    Full Text Available PURPOSES: To describe corneal changes seen on in vivo confocal microscopy in patients with total limbal stem cell deficiency and to correlate them with cytological findings. METHODS: A prospective case series including 13 eyes (8 patients with total limbal deficiency was carried out. Stem cell deficiency was diagnosed clinically and by corneal impression cytology. Confocal images of the central cornea were taken with the Heidelberg Retina Tomograph II, Rostock Corneal Module (Heidelberg Engineering, Heidelberg, Germany. RESULTS: Impression cytology of the cornea revealed conjunctival epithelial cells and goblet cells in all cases. In vivo confocal microscopy showed disruption of normal layers of the corneal epithelium in all eyes. Confocal images showed cells with characteristics of conjunctival epithelium at the cornea in 76.9% of the total. These findings on confocal microscopy were compatible to limbal stem cell deficiency. Additionally, goblet cells, squamous metaplasia, inflammatory cells and dendritic cells were observed. The sub-basal nerve plexus was not identified in any of the corneas. Corneal neovessels were observed at the epithelium and stroma. All cases showed diffuse hyper-reflective images of the stroma corresponding to opacity of the tissue. CONCLUSIONS: Limbal stem cell deficiency had been confirmed by impression cytology in all cases, and 76.9% of the cases could also be diagnosed by in vivo confocal microscopy through the conjunctival epithelial cell visualization on the corneal surface. Frequent confocal microscopy findings were abnormal cells at the cornea (conjunctival epithelial, goblet and inflammatory cells, corneal neovessels and diffuse hyper-reflection of the stroma.

  19. Biomechanics and biorheology of red blood cells in sickle cell anemia

    Science.gov (United States)

    Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

    2017-01-01

    Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis. PMID:27876368

  20. Biomechanics and biorheology of red blood cells in sickle cell anemia.

    Science.gov (United States)

    Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

    2017-01-04

    Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis.

  1. A micro-scale simulation of red blood cell passage through symmetric and asymmetric bifurcated vessels

    CERN Document Server

    Wang, Tong; Xing, Zhongwen

    2016-01-01

    Blood exhibits a heterogeneous nature of hematocrit, velocity, and effective viscosity in microcapillaries. Microvascular bifurcations have a significant influence on the distribution of the blood cells and blood flow behavior. This paper presents a simulation study performed on the two-dimensionalmotions and deformation of multiple red blood cells in microvessels with diverging and converging bifurcations. Fluid dynamics and membrane mechanics were incorporated. Effects of cell shape, hematocrit, and deformability of the cell membrane on rheological behavior of the red blood cells and the hemodynamics have been investigated. It was shown that the blood entering the daughter branch with a higher flow rate tended to receive disproportionally more cells. The results also demonstrate that red blood cells in microvessels experienced lateral migration in the parent channel and blunted velocity profiles in both straight section and daughter branches, and this effect was influenced by the shape and the initial posit...

  2. Neutral red uptake assay for the estimation of cell viability/cytotoxicity.

    Science.gov (United States)

    Repetto, Guillermo; del Peso, Ana; Zurita, Jorge L

    2008-01-01

    The neutral red uptake assay provides a quantitative estimation of the number of viable cells in a culture. It is one of the most used cytotoxicity tests with many biomedical and environmental applications. It is based on the ability of viable cells to incorporate and bind the supravital dye neutral red in the lysosomes. Most primary cells and cell lines from diverse origin may be successfully used. Cells are seeded in 96-well tissue culture plates and are treated for the appropriate period. The plates are then incubated for 2 h with a medium containing neutral red. The cells are subsequently washed, the dye is extracted in each well and the absorbance is read using a spectrophotometer. The procedure is cheaper and more sensitive than other cytotoxicity tests (tetrazolium salts, enzyme leakage or protein content). Once the cells have been treated, the assay can be completed in <3 h.

  3. Deficiency in Homologous Recombination Renders Mammalian Cells More Sensitive to Proton Versus Photon Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Grosse, Nicole; Fontana, Andrea O. [Laboratory for Molecular Radiobiology, University Hospital Zurich, Zurich (Switzerland); Hug, Eugen B.; Lomax, Antony; Coray, Adolf [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Augsburger, Marc [Laboratory for Molecular Radiobiology, University Hospital Zurich, Zurich (Switzerland); Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Sartori, Alessandro A. [Institute of Molecular Cancer Research, University of Zurich, Zurich (Switzerland); Pruschy, Martin, E-mail: martin.pruschy@usz.ch [Laboratory for Molecular Radiobiology, University Hospital Zurich, Zurich (Switzerland)

    2014-01-01

    Purpose: To investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation. Methods and Materials: The DNA repair and cell survival endpoints in wild-type, homologous recombination (HR)-deficient, and nonhomologous end-joining-deficient cells were analyzed after irradiation with clinically relevant, low-linear energy transfer (LET) protons and 200-keV photons. Results: All cell lines were more sensitive to proton irradiation compared with photon irradiation, despite no differences in the induction of DNA breaks. Interestingly, HR-deficient cells and wild-type cells with small interfering RNA-down-regulated Rad51 were markedly hypersensitive to proton irradiation, resulting in an increased relative biological effectiveness in comparison with the relative biological effectiveness determined in wild-type cells. In contrast, lack of nonhomologous end-joining did not result in hypersensitivity toward proton irradiation. Repair kinetics of DNA damage in wild-type cells were equal after both types of irradiation, although proton irradiation resulted in more lethal chromosomal aberrations. Finally, repair kinetics in HR-deficient cells were significantly delayed after proton irradiation, with elevated amounts of residual γH2AX foci after irradiation. Conclusion: Our data indicate a differential quality of DNA damage by proton versus photon irradiation, with a specific requirement for homologous recombination for DNA repair and enhanced cell survival. This has potential relevance for clinical stratification of patients carrying mutations in the DNA damage response pathways.

  4. Biologic characteristic studies of DNA mismatch—repair enzyme hMSH2—deficient cell strain

    Institute of Scientific and Technical Information of China (English)

    HeY; ZhuaZX

    2002-01-01

    The effect of hMSH2 enzyme-deficiency on the cell growing phenotypes,cell ultrastructure,growth character and cell cycle were observed with electronic microscopy examination,cell counting and flow cytometry.hMSH2-deficient cell strain was constructed by transfecting hMSH2 recombination plasmid of antisense RNA into human embryo lung fibroblasts(HLF).In hMSH2-deficient cells,there were a lot of morphological changes under electronic microscopy,such as irregular shape,a lot of protuberances on the surface of cell,the enlarged nuclei.The average time of double increment of HLF and hMSH2-deficient cells were 1.0d and 0.78d,respectively.This suggested that the cell proliferation of hMSH2-deficient cells was greater than that of HLF.The distribution of HLF and hMSH2-deficient cells in G1,G2 and S phases was different.A large part of hMSH2-deficient cells was blocked in G1 phase.hMSH2-deficient cells increased,but it is still not a typical malignant cells.Thus,this cell strain could be used as biologic material to detect mutagenesis of environmental chemicals.

  5. Pure red cell aplasia in a simultaneous pancreas-kidney transplantation patient: inside the erythroblast

    Directory of Open Access Journals (Sweden)

    Francesca Labbadia

    2012-09-01

    Full Text Available A case of pure red cell aplasia in a simultaneous kidney-pancreas transplant recipient on immunosuppressive therapy is reported here. The patient presented with anemia unresponsive to erythropoietin treatment. Bone marrow cytomorphology was highly suggestive of parvovirus pure red cell aplasia, which was confirmed with serology and polymerase chain reaction positive for parvovirus B19 DNA in peripheral blood. After the administration of intravenous immunoglobulin the anemia improved with a rising number of the reticulocytes.

  6. Effect of Packed Red Blood Cell Cryopreservation on Development of the Storage Lesion and Inflammation

    Science.gov (United States)

    2015-09-01

    liquid storage on development of the biochemical, metabolic, and morphologic changes collectively known as the red blood cell storage lesion is unknown...adjunct to standard blood banking techniques. The post-thaw characteristics are markedly different than fresh packed red blood cells, and the...Drug Administration currently restricts their use to 14 days after thawing. The effect of longer term liquid storage on development of the

  7. [Acute hepatitis-associated pure red cell aplasia: a case report].

    Science.gov (United States)

    Della Loggia, Paolo; Cremonini, Laura

    2002-12-01

    After a holiday in Egypt, a 57-year-old caucasian woman developed acute hepatitis A. The illness seemed initially to have a benign course, with a decreasing trend of hepatic enzymes and an apparent recovery. Three weeks later a relapse occurred. Recurrence of symptoms and aminotransferase elevation were associated with severe anemia; a hyporegenerative anemia was diagnosed and all laboratory findings were consistent with pure red cell aplasia. The haematologic disorder was successfully treated with red cell transfusion and glucocorticoids.

  8. Dynamical Modes of Deformed Red Blood Cells and Lipid Vesicles in Flows

    Science.gov (United States)

    Noguchi, H.

    Red blood cells and lipid vesicles exhibit rich behaivor in flows.Their dynamics were studied using a particle-based hydrodynamic simulation method, multi-particle collision dynamics. Rupture of lipid vesicles in simple shear flow was simulated by meshless membrane model. Several shape transitions of lipid vesicles and red blood cells are induced by flows. Transition of a lipid vesicle from budded to prolate shapes with increasing shear rate and ordered alignments of deformed elastic vesicles in high density are presented.

  9. Anesthetic management of a pregnant patient with a pure red cell aplasia

    Directory of Open Access Journals (Sweden)

    Channabasavaraj S Sanikop

    2013-01-01

    Full Text Available Pure red cell disorder is an uncommon disorder in which maturation arrest occurs in the maturation of erythrocytes. Erythroblats are virtually absent in the bone marrow. Surgery poses a very high-risk for these patients because of the several complications that can occur in the perioperative period. In this case report, we report a pregnant patient with a pure red cell aplasia who was optimized pre-operatively and underwent cesarean section under sub-arachnoid block.

  10. Duration of red blood cell storage and survival of transfused patients (CME)

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Kamper-Jørgensen, Mads; Eloranta, Sandra;

    2010-01-01

    Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time.......Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time....

  11. Seventy-five genetic loci influencing the human red blood cell

    OpenAIRE

    van der Harst, Pim; Zhang, Weihua; Mateo Leach, Irene; Rendon, Augusto; Verweij, Niek; Sehmi, Joban; Dirk S Paul; Elling, Ulrich; Allayee, Hooman; Li, Xinzhong; Radhakrishnan, Aparna; Tan, Sian-Tsung; Voss, Katrin; Weichenberger, Christian X.; Albers, Cornelis A

    2012-01-01

    Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phe...

  12. The role of red cell distribution width as a marker in inflammatory bowel disease

    OpenAIRE

    Arhan, Mehmet; ÖNAL, İbrahim Koral; Taş, Adnan; KURT, Mevlüt; Kalkan, İsmail Hakkı

    2011-01-01

    To determine whether red cell distribution width could be used for the assessment of disease activity in patients with inflammatory bowel disease. Materials and methods: A total of 165 patients with inflammatory bowel disease (105 ulcerative colitis; 60 Crohn's disease) and 43 healthy blood donors were included in this retrospective study in a tertiary care setting. The medical records of the patients were reviewed to note clinical activity indices, red cell distribution width, serum C ...

  13. Mechanical and electrical properties of red blood cells using optical tweezers

    Science.gov (United States)

    Fontes, A.; Barjas Castro, M. L.; Brandão, M. M.; Fernandes, H. P.; Thomaz, A. A.; Huruta, R. R.; Pozzo, L. Y.; Barbosa, L. C.; Costa, F. F.; Saad, S. T. O.; Cesar, C. L.

    2011-04-01

    Optical tweezers are a very sensitive tool, based on photon momentum transfer, for individual, cell by cell, manipulation and measurements, which can be applied to obtain important properties of erythrocytes for clinical and research purposes. Mechanical and electrical properties of erythrocytes are critical parameters for stored cells in transfusion centers, immunohematological tests performed in transfusional routines and in blood diseases. In this work, we showed methods, based on optical tweezers, to study red blood cells and applied them to measure apparent overall elasticity, apparent membrane viscosity, zeta potential, thickness of the double layer of electrical charges and adhesion in red blood cells.

  14. Removal of antibodies from red cells: Comparison of three elution methods

    Directory of Open Access Journals (Sweden)

    Rahul Katharia

    2013-01-01

    Full Text Available Background: Direct antiglobulin test (DAT is the most common test done in immunohematology lab, which detects immunoglobulin and fragments of complement attached to the red blood cells. These coated red blood cells are difficult to accurately phenotype, which may be required for selection of appropriate unit of red blood cells for transfusion. Aims: We have studied the efficacy of various elution methods in removing the antibodies coating the red cells and their impact on different blood group antigen activity. Materials and Methods: Patient samples sent for serological evaluation of autoimmune hemolysis were included in the study. DAT and Indirect antiglobulin test (IAT were performed using gel cards (ID system, DiaMed Switzerland. Antibody coated red cells, either by in-vivo or in-vitro sensitization, were used to assess the outcome of three elution methods. Results: Out of 93 DAT positive samples already sensitized in vivo, 28 (30 % samples became DAT negative post elution using either of three methods, while 36 (38.8% showed reduction in strength of reaction, whereas in 29 (31.2% there was no change in strength of reaction. Similarly, out of the 17 samples prepared by in vitro sensitization, 12 samples became completely negative after glycine-HCl/EDTA elution, 9 and 5 samples became negative after heat elution and chloroquine diphosphate elution methods, respectively. Conclusion: On comparative analysis glycine-HCl/EDTA elution method was better than the other two methods and can be used for eluting immunoglobulins from intact red cells.

  15. An effect of glycoprotein IIb/IIIa inhibitors on the kinetics of red blood cells aggregation.

    Science.gov (United States)

    Sokolova, Irina A; Muravyov, Alexei V; Khokhlova, Maria D; Rikova, Sofya Yu; Lyubin, Evgeny V; Gafarova, Marina A; Skryabina, Maria N; Fedyanin, Angrey A; Kryukova, Darya V; Shahnazarov, Alexander A

    2014-01-01

    The reversible aggregation of red blood cells (RBCs) continues to be of the basic science and clinical interest. Recently it has been reported about a specific binding between fibrinogen and unknown erythrocyte glycoprotein receptors. The aim of this study was to investigate whether the red blood cell aggregation (RBCA) include the cell-cell interaction using the membrane receptors that bind such ligands as fibrinogen or fibronectin. To test this hypothesis the RBCs were incubated with monafram - the drug of the monoclonal antibodies against glycoprotein (GP) IIb/IIIa, with the GPIIb-IIIa receptor antagonist tirofiban, epifibatide and with the fibrinogen inhibiting peptide. It has been found that the RBC incubation with monafram resulted in a marked RBCA decrease mainly in persons with high level of aggregation. Another research session has shown that RBC incubation with fibronectin was accompanied by a significant RBCA rise. The monafram addition to red cell incubation medium resulted in a significant RBCA lowering. The cell incubation with tirofiban and epifibatide issued in RBCA decrease. The similar results were obtained when RBCs were incubated with the fibrinogen inhibiting peptide. Although monafram, tirofiban, eptifibatide and the fibrinogen inhibiting peptide were related to fibrinogen function they didn't inhibit RBCA completely. Therefore, under moderate and low red blood cell aggregation the cell binding is probably related to nonspecific mode. It seems evident that the specific and nonspecific modes of red blood cell aggregate formation could co-exist. Additional theoretical and experimental investigations in this area are needed.

  16. B-cell development and functions and therapeutic options in adenosine deaminase-deficient patients

    NARCIS (Netherlands)

    I. Brigida (Immacolata); A.V. Sauer (Aisha); F. Ferrua (Francesca); S. Giannelli (Stefania); S. Scaramuzza (Samantha); V. Pistoia (Valentina); M.C. Castiello (Maria Carmina); B.H. Barendregt (Barbara); M.P. Cicalese (Maria Pia); F. Casiraghi (Federica); C. Brombin (Chiara); J. Puck (Jennifer); K. Muller (Karin); L.D. Notarangelo (Luigi Daniele); D. Montin (Davide); J.M. van Montfrans (Joris); M.G. Roncarolo (Maria Grazia); E. Traggiai (Elisabetta); J.J.M. van Dongen (Jacques); M. van der Burg (Mirjam); A. Aiuti (Alessandro)

    2014-01-01

    textabstractBackground Adenosine deaminase (ADA) deficiency causes severe cellular and humoral immune defects and dysregulation because of metabolic toxicity. Alterations in B-cell development and function have been poorly studied. Enzyme replacement therapy (ERT) and hematopoietic stem cell (HSC) g

  17. Culture of Oral Mucosal Epithelial Cells for the Purpose of Treating Limbal Stem Cell Deficiency

    Directory of Open Access Journals (Sweden)

    Tor Paaske Utheim

    2016-03-01

    Full Text Available The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC, which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD. Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells.

  18. Culture of Oral Mucosal Epithelial Cells for the Purpose of Treating Limbal Stem Cell Deficiency.

    Science.gov (United States)

    Utheim, Tor Paaske; Utheim, Øygunn Aass; Khan, Qalb-E-Saleem; Sehic, Amer

    2016-03-01

    The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS) represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells.

  19. TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells.

    Science.gov (United States)

    Haruta, M; Tomita, Y; Yuno, A; Matsumura, K; Ikeda, T; Takamatsu, K; Haga, E; Koba, C; Nishimura, Y; Senju, S

    2013-05-01

    We previously reported a method to generate dendritic cell (DC)-like antigen-presenting cells (APC) from human induced pluripotent stem (iPS) cells. However, the method is relatively complicated and laborious. In the current study, we attempted to establish a method through which we could obtain a large number of functional APC with a simple procedure. We transduced iPS cell-derived CD11b(+) myeloid cells with genes associated with proliferative or anti-senescence effects, enabling the cells to propagate for more than 4 months in a macrophage colony-stimulating factor (M-CSF)-dependent manner while retaining their capacity to differentiate into functional APC. We named these iPS cell-derived proliferating myeloid cells 'iPS-ML', and the iPS-ML-derived APC 'ML-DC'. In addition, we generated TAP2-deficient iPS cell clones by zinc finger nuclease-aided targeted gene disruption. TAP2-deficient iPS cells and iPS-ML avoided recognition by pre-activated allo-reactive CD8(+) T cells. TAP2-deficient ML-DC expressing exogenously introduced HLA-A2 genes stimulated HLA-A2-restricted MART-1-specific CD8(+) T cells obtained from HLA-A2-positive allogeneic donors, resulting in generation of MART-1-specific cytotoxic T lymphocyte (CTL) lines. TAP-deficient iPS-ML introduced with various HLA class I genes may serve as an unlimited source of APC for vaccination therapy. If administered into allogeneic patients, ML-DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and, after that, be completely eliminated. Based on the present study, we propose an APC-producing system that is simple, safe and applicable to all patients irrespective of their HLA types.

  20. A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice.

    Directory of Open Access Journals (Sweden)

    Andreas Greth

    Full Text Available The blood stage of the plasmodium parasite life cycle is responsible for the clinical symptoms of malaria. Epidemiological studies have identified coincidental malarial endemicity and multiple red blood cell (RBC disorders. Many RBC disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections. However the mechanisms underpinning these genetic, host responses remain obscure. We have performed an N-ethyl-N-nitrosourea (ENU mutagenesis screen and have identified a novel dominant (haploinsufficient mutation in the Ank-1 gene (Ank1(MRI23420 of mice displaying hereditary spherocytosis (HS. Female mice, heterozygous for the Ank-1 mutation showed increased survival to infection by Plasmodium chabaudi adami DS with a concomitant 30% decrease in parasitemia compared to wild-type, isogenic mice (wt. A comparative in vivo red cell invasion and parasite growth assay showed a RBC-autonomous effect characterised by decreased proportion of infected heterozygous RBCs. Within approximately 6-8 hours post-invasion, TUNEL staining of intraerythrocytic parasites, showed a significant increase in dead parasites in heterozygotes. This was especially notable at the ring and trophozoite stages in the blood of infected heterozygous mutant mice compared to wt (p<0.05. We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites.

  1. Red light-induced redox reactions in cells observed with TEMPO.

    Science.gov (United States)

    Eichler, Maor; Lavi, Ronit; Friedmann, Harry; Shainberg, Asher; Lubart, Rachel

    2007-06-01

    The aim of this study was to determine the wavelength dependence of light-induced redox reactions in cells, particularly whether there is any contribution by red wavelengths. An additional aim was to assess the potential of 2,2,6,6-tetramethyl piperidine-N-oxyl (TEMPO) as a tool for measuring these redox reactions. Visible light has been shown to affect cells, and redox reactions, which have been detected previously using spin traps, have been proposed as a mechanism. However, there is little evidence that red light, which is used in most such experiments, is redox active in cells. Redox activity was observed by measuring the decay of the electron paramagnetic resonance signal of TEMPO that occurs in the presence of illuminated cells. Color filters were used to generate blue, green, and red light, and the decay resulting from these wavelengths was compared to the decay caused by white light. Shorter wavelengths have a considerably stronger effect than longer wavelengths, although red light has some effect. Creation of reactive oxygen species by red light was confirmed with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Red light can induce redox reactions in illuminated cells. However, shorter wavelengths are more efficient in this regard. In addition, TEMPO was found to be a more sensitive probe than DMPO for detecting light-induced cellular redox reactions.

  2. Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions.

    Science.gov (United States)

    Górski, A; Castronovo, V; Stepień-Sopniewska, B; Grieb, P; Ryba, M; Mrowiec, T; Korczak-Kowalska, G; Wierzbicki, P; Matysiak, W; Dybowska, B

    1994-07-01

    Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.

  3. Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells.

    Science.gov (United States)

    Giani, Felix C; Fiorini, Claudia; Wakabayashi, Aoi; Ludwig, Leif S; Salem, Rany M; Jobaliya, Chintan D; Regan, Stephanie N; Ulirsch, Jacob C; Liang, Ge; Steinberg-Shemer, Orna; Guo, Michael H; Esko, Tõnu; Tong, Wei; Brugnara, Carlo; Hirschhorn, Joel N; Weiss, Mitchell J; Zon, Leonard I; Chou, Stella T; French, Deborah L; Musunuru, Kiran; Sankaran, Vijay G

    2016-01-07

    Multipotent and pluripotent stem cells are potential sources for cell and tissue replacement therapies. For example, stem cell-derived red blood cells (RBCs) are a potential alternative to donated blood, but yield and quality remain a challenge. Here, we show that application of insight from human population genetic studies can enhance RBC production from stem cells. The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation. Our findings therefore highlight the potential for combining human genome variation studies with genome editing approaches to improve cell and tissue production for regenerative medicine.

  4. Aberrant recombination and repair during immunoglobulin class switching in BRCA1-deficient human B cells

    DEFF Research Database (Denmark)

    Björkman, Andrea; Qvist, Per; Du, Likun

    2015-01-01

    machinery. A shift to the use of microhomology-based, alternative end-joining (A-EJ) and increased frequencies of intra-S region deletions as well as insertions of inverted S sequences were observed at the recombination junctions amplified from BRCA1-deficient human B cells. Furthermore, increased use...... underlying BRCA1’s function in maintaining genome stability and tumor suppression but may also point to a previously unrecognized role of BRCA1 in B-cell lymphomagenesis....... of long microhomologies was found at recombination junctions derived from E3 ubiquitin-protein ligase RNF168-deficient, Fanconi anemia group J protein (FACJ, BRIP1)-deficient, or DNA endonuclease RBBP8 (CtIP)-compromised cells, whereas an increased frequency of S-region inversions was observed in breast...

  5. ROCK1 deficiency enhances protective effects of antioxidants against apoptosis and cell detachment.

    Directory of Open Access Journals (Sweden)

    Michelle Surma

    Full Text Available We have recently reported that the homologous Rho kinases, ROCK1 and ROCK2, play different roles in regulating stress-induced stress fiber disassembly and cell detachment, and the ROCK1 deficiency in mouse embryonic fibroblasts (MEF has remarkable anti-apoptotic, anti-detachment and pro-survival effects against doxorubicin, a chemotherapeutic drug. This study investigated the roles of ROCK isoforms in doxorubicin-induced reactive oxygen species (ROS generation which is believed to be the major mechanism underlying its cytotoxicity to normal cells, and especially to cardiomyocytes. Different antioxidants have been shown to provide a protective role reported in numerous experimental studies, but clinical trials of antioxidant therapy showed insufficient benefit against the cardiac side effect. We found that both ROCK1-/- and ROCK2-/- MEFs exhibited reduced ROS production in response to doxorubicin treatment. Interestingly, only ROCK1 deficiency, but not ROCK2 deficiency, significantly enhanced the protective effects of antioxidants against doxorubicin-induced cytotoxicity. First, ROCK1 deficiency and N-acetylcysteine (an anti-oxidant treatment synergistically reduced ROS levels, caspase activation and cell detachment. In addition, the reduction of ROS generation in ROCK1-/- MEFs in response to doxorubicin treatment was in part through inhibiting NADPH oxidase activity. Furthermore, ROCK1 deficiency enhanced the inhibitory effects of diphenyleneiodonium (an inhibitor of NADPH oxidase on ROS generation and caspase 3 activation induced by doxorubicin. Finally, ROCK1 deficiency had greater protective effects than antioxidant treatment, especially on reducing actin cytoskeleton remodeling. ROCK1 deficiency not only reduced actomyosin contraction but also preserved central stress fiber stability, whereas antioxidant treatment only reduced actomyosin contraction without preserving central stress fibers. These results reveal a novel strategy to enhance

  6. Hybrid SPECT-CT with 99mTc-labeled red blood cell in a case of blue rubber bleb nevus syndrome: added value over planar scintigraphy.

    Science.gov (United States)

    Das, Kalpa Jyoti; Sharma, Punit; Naswa, Niraj; Soundararajan, Ramya; Kumar, Rakesh; Bal, Chandrasekhar; Malhotra, Arun

    2013-01-01

    Blue rubber bleb nevus syndrome (BRBNS) is a rare clinical entity characterized by multiple venous malformations (hemangiomas) of the skin and gastrointestinal tract. These hemangiomas usually cause episodes of occult gastrointestinal bleeding leading to iron deficiency anemia, and also carry a significant potential for serious hemorrhage. The 99mechnetium (99mTc)-labeled red blood cell scintigraphy has traditionally been utilized in the localization of occult bleeding sites in patients with suspected vascular malformations, angiodysplasia, and Meckel’s diverticulum. We report the incremental value of 99mTc-labeled red blood cell hybrid single-photon emission computed tomography-computed tomography (SPECT-CT) over planar scintigraphy alone in a 12-year-old female patient with BRBNS.

  7. Early alterations of red blood cell rheology in critically ill patients.

    Science.gov (United States)

    Reggiori, Giulia; Occhipinti, Giovanna; De Gasperi, Andrea; Vincent, Jean-Louis; Piagnerelli, Michael

    2009-12-01

    To investigate red blood cell rheology in a large intensive care unit population on admission, and to assess the possible influence of comorbidities on the rheology. : Prospective study. Medico-surgical intensive care unit with 31 beds. All intensive care unit admissions during a 5-month period and 20 healthy volunteers. Blood sampling. A total of 196 intensive care patients (160 without and 36 with sepsis) and 20 healthy volunteers were studied. Red blood cell rheology (deformability and aggregation) was assessed ex vivo using the laser-assisted optical rotational cell analyzer (LORCA; Mechatronics Instruments BV, AN Zwaag, Netherlands) within the first 24 hrs after intensive care unit admission. Red blood cell deformability was determined by the elongation index in relation to the shear stress (0.3 to 50 Pa) applied on the red blood cell membrane surface. Aggregation was assessed by the aggregation index. Septic patients were more likely to have anemia, coagulation abnormalities, and comorbidities than were nonseptic patients. Red blood cell deformability was significantly altered in septic compared to nonseptic patients and volunteers for the majority of shear stress rates studied. The aggregation index was greater in septic patients than in volunteers (67.9% [54.7-73.5] vs. 61.8% [58.2-68.4]; p < .05). Only sepsis and hematologic disease influenced the elongation index (both p < .01). Other comorbidities, like cancer, diabetes mellitus, cirrhosis, and terminal renal failure, had no effect on the elongation index. Aggregation index was related to the degree of organ failure (Sequential Organ Failure Assessment score), the red blood cell count, and fibrinogen concentrations. Early alterations of red blood cell rheology are common in intensive care unit patients, especially in those with sepsis. Comorbidities (other than hematologic diseases) do not significantly influence these abnormalities. These alterations could contribute to the microcirculatory alterations

  8. Red Blood Cell Transfusions in Greece: Results of a Survey of Red Blood Cell Use in 2013

    Directory of Open Access Journals (Sweden)

    Serena Valsami

    2017-03-01

    Full Text Available Objective: Greece is ranked as the second highest consumer of blood components in Europe. For an effective transfusion system and in order to reduce variability of transfusion practice by implementing evidence-based transfusion guidelines it is necessary to study and monitor blood management strategies. Our study was conducted in order to evaluate the use of red blood cell units (RBC-U in nationwide scale mapping parameters that contribute to their proper management in Greece. Materials and Methods: The survey was conducted by the Working Committee of Transfusion Medicine&Apheresis of the Hellenic Society of Hematology from January to December 2013. The collected data included the number, ABO/D blood group, patients’ department, and storage age of RBC-U transfused. Results: The number of RBC-U evaluated was 103,702 (17.77% out of 583,457 RBC-U transfused in Greece in 2013. RBC-U transfused by hospital department (mean percentage was as follows: Surgery 29.34%, Internal Medicine 29.48%, Oncology/Hematology 14.65%, Thalassemia 8.87%, Intensive Care Unit 6.55%, Nephrology 1.78%, Obstetrics/Gynecology 1.46%, Neonatal&Pediatric 0.31%, Private Hospitals 8.57%. RBC-U distribution according to ABO/D blood group was: A: 39.02%, B: 12.41%, AB: 5.16%, O: 43.41%, D+: 87.99%, D-: 12.01%. The majority of RBC-U (62.46% was transfused in the first 15 days of storage, 25.24% at 16 to 28 days, and 12.28% at 29-42 days. Conclusion: Despite a high intercenter variability in RBC transfusions, surgical and internal medicine patients were the most common groups of patients transfused with an increasing rate for internal medicine patients. The majority of RBC-U were transfused within the first 15 days of storage, which is possibly the consequence of blood supply insufficiency leading to the direct use of fresh blood. Benchmarking transfusion activity may help to decrease the inappropriate use of blood products, reduce the cost of care, and optimize the use of the

  9. Detection of Plasmodium falciparum-infected red blood cells by optical stretching

    Science.gov (United States)

    Mauritz, Jakob M. A.; Tiffert, Teresa; Seear, Rachel; Lautenschläger, Franziska; Esposito, Alessandro; Lew, Virgilio L.; Guck, Jochen; Kaminski, Clemens F.

    2010-05-01

    We present the application of a microfluidic optical cell stretcher to measure the elasticity of malaria-infected red blood cells. The measurements confirm an increase in host cell rigidity during the maturation of the parasite Plasmodium falciparum. The device combines the selectivity and sensitivity of single-cell elasticity measurements with a throughput that is higher than conventional single-cell techniques. The method has potential to detect early stages of infection with excellent sensitivity and high speed.

  10. Membrane rigidity of red blood cells parasitized by different strains of Plasmodium falciparum.

    Science.gov (United States)

    Paulitschke, M; Nash, G B

    1993-11-01

    Changes in the structure of parasitized red blood cells may influence their ability to circulate. We have used a micropipette technique to examine the effects of invasion and maturation of Plasmodium falciparum on the membrane rigidity of red blood cells. In the presence of immature, ring form parasites from different laboratory strains, membrane rigidity remained unchanged as compared with uninfected red cells. However, development of more mature pigmented trophozoites caused a marked increase in membrane rigidity. Parasites from knobless strains caused a less-pronounced increase than parasites from knob-positive strains. Using closely synchronized cultures, the dependence of membrane rigidity on parasite maturation was studied in more detail for selected knob-positive and knobless strains. Over a period of 12 hours, while trophozoites developed into schizonts, no further rigidification of the red cell membrane occurred. The increase in membrane rigidity, occurring with the initial development of pigmented trophozoites, may be related to insertion of neoantigens into the red cell surface or modification of native membrane proteins that also occur at this time. In contrast to others, we found no effect of parasite-culture supernatant, harvested at different stages, on the rigidity of uninfected cells exposed to it. Interstrain variation of membrane rigidity could influence pathophysiology in several ways: by promoting margination and cytoadherence of knob-positive strains in the microcirculation, by modulating clearance of parasitized cells by the reticuloendothelial system, and by influencing ischemic complications of severe falciparum malaria.

  11. Copper deficiency alters cell bioenergetics and induces mitochondrial fusion through up-regulation of MFN2 and OPA1 in erythropoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Bustos, Rodrigo I.; Jensen, Erik L.; Ruiz, Lina M.; Rivera, Salvador; Ruiz, Sebastián [Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago (Chile); Simon, Felipe; Riedel, Claudia [Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago (Chile); Millennium Institute of Immunology and Immunotherapy, Santiago (Chile); Ferrick, David [Seahorse Bioscience, Billerica, MA (United States); Elorza, Alvaro A., E-mail: aelorza@unab.cl [Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago (Chile); Millennium Institute of Immunology and Immunotherapy, Santiago (Chile)

    2013-08-02

    Highlights: •In copper deficiency, cell proliferation is not affected. In turn, cell differentiation is impaired. •Enlarged mitochondria are due to up-regulation of MNF2 and OPA1. •Mitochondria turn off respiratory chain and ROS production. •Energy metabolism switch from mitochondria to glycolysis. -- Abstract: Copper is essential in cell physiology, participating in numerous enzyme reactions. In mitochondria, copper is a cofactor for respiratory complex IV, the cytochrome c oxidase. Low copper content is associated with anemia and the appearance of enlarged mitochondria in erythropoietic cells. These findings suggest a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis, which has not been explored so far. Here, we describe that bathocuproine disulfonate-induced copper deficiency does not alter erythropoietic cell proliferation nor induce apoptosis. However it does impair erythroid differentiation, which is associated with a metabolic switch between the two main energy-generating pathways. That is, from mitochondrial function to glycolysis. Switching off mitochondria implies a reduction in oxygen consumption and ROS generation along with an increase in mitochondrial membrane potential. Mitochondrial fusion proteins MFN2 and OPA1 were up-regulated along with the ability of mitochondria to fuse. Morphometric analysis of mitochondria did not show changes in total mitochondrial biomass but rather bigger mitochondria because of increased fusion. Similar results were also obtained with human CD34+, which were induced to differentiate into red blood cells. In all, we have shown that adequate copper levels are important for maintaining proper mitochondrial function and for erythroid differentiation where the energy metabolic switch plus the up-regulation of fusion proteins define an adaptive response to copper deprivation to keep cells alive.

  12. The effect of iron-deficiency anemia on cytolytic activity of mice spleen and peritoneal cells against allogenic tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuvibidila, S.R.; Baliga, B.S.; Suskind, R.M.

    1983-08-01

    The capacity of spleen and peritoneal cells from iron deficient mice, ad libitum fed control mice, and pair-fed mice to kill allogenic tumor cells (mastocytoma tumor P815) has been investigated. In the first study, mice were sensitized in vivo with 10(7) viable tumor cells 51 and 56 days after weaning. The capacity of splenic cells and peritoneal cells from sensitized and nonsensitized mice to kill tumor cells was evaluated 5 days after the second dose of tumor cells. At ratios of 2.5:1 to 100:1 of attacker to target cells, the percentage /sup 51/Cr release after 4 h of incubation was significantly less in iron-deficient mice than control and/or pair-fed mice (p less than 0.05). Protein-energy undernutrition in pair-fed mice had no significant effect. In the second study, spleen cells and enriched T cell fractions were incubated in vitro for 5 days with uv irradiated Balb/C spleen cells in a 2:1 ratio. The cytotoxic capacity against the same allogenic tumor cells was again evaluated. The percentage chromium release at different attacker to target cells was less than 30% in the iron-deficient group compared to either control or pair-fed supporting the results of in vivo sensitized cells. The possible mode of impairment of the cytotoxic capacity is discussed.

  13. Optically-driven red blood cell rotor in linearly polarized laser tweezers

    Indian Academy of Sciences (India)

    Manas Khan; Samarendra K Mohanty; A K Sood

    2005-11-01

    We have constructed a dual trap optical tweezers set-up around an inverted microscope where both the traps can be independently controlled and manipulated in all the three dimensions. Here we report our observations on rotation of red blood cells (RBCs) in a linearly polarized optical trap. Red blood cells deform and become twisted in hypertonic phosphate buffer saline and when trapped, experience an unbalanced radiation pressure force. The torque generated from the unbalanced force causes the trapped RBC to rotate. Addition of Ca++ ions in the solution, keeping the osmolarity same, makes the cell membranes stiffer and the cells deform less. Thus the speed of rotation of the red blood cells can be controlled, as less deformation and in turn less asymmetry in shape produces less torque under the radiation pressure resulting in slower rotation at the same laser power.

  14. Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency.

    Science.gov (United States)

    Jiang, Dewei; Zhang, Ying; Hart, Ronald P; Chen, Jianmin; Herrup, Karl; Li, Jiali

    2015-12-01

    A long-standing mystery surrounding ataxia-telangiectasia is why it is mainly cerebellar neurons, Purkinje cells in particular, that appear vulnerable to ATM deficiency. Here we present data showing that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human ataxia-telangiectasia and Atm(-/-) mouse cerebellar Purkinje cells. We further show that TET1, an enzyme that converts 5-methylcytosine (5mC) to 5hmC, responds to DNA damage and manipulation of TET1 activity directly affects the DNA damage signalling and ATM-deficient neuronal cell cycle re-entry and death. Quantitative genome-wide analysis of 5hmC-containing sequences shows that in ATM deficiency there is a cerebellum- and Purkinje cell-specific shift in 5hmC enrichment in both regulatory elements and repeated sequences. Finally, we verify that TET1-mediated 5hmC production is linked to the degenerative process of Purkinje cells and behavioural deficits in Atm(-/-) mice. Taken together, the selective loss of 5hmC plays a critical role in driving Purkinje cell vulnerability in ATM deficiency.

  15. Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Wei-Ren Li; Zhe-Zhu Gao; Zhong-Cheng Xin; Liang Chen; Zhi-Jie Chang; Hua Xin; Tao Liu; Yan-Quan Zhang; Guang-Yong Li; Feng Zhou; Yan-Qing Gong

    2011-01-01

    Late-onset hypogonadism (LOH) is closely related to secondary androgen deficiency in aged males,but the mechanism remains unclear.In this study,we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity.Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production.In Leydig cells from young and aged rats,treatment with wortmannin,an autophagy inhibitor,inhibited luteinising hormone (LH)-stimulated steroidogenic acute regulatory (StAR) protein expression and decreased testosterone production.In contrast,treatment with rapamycin,an autophagy activator,enhanced LH-stimulated steroidogenesis in Leydig cells from aged,but not young,rats.Intracellular reactive oxygen species (ROS) levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin.Furthermore,an increased level of ROS,induced by H2O2,resulted in LH-stimulated steroidogenic inhibition.Finally,knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells,which were associated with increased intracellular ROS level.These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells,which might be influenced by intracellular ROS levels.

  16. Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4

    Directory of Open Access Journals (Sweden)

    Zhijing Liu

    2015-01-01

    Full Text Available Shortage of red blood cells (RBCs, erythrocytes can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs, but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.

  17. In-vitro stem cell derived red blood cells for transfusion: are we there yet?

    Science.gov (United States)

    Kim, Hyun Ok

    2014-03-01

    To date, the use of red blood cells (RBCs) produced from stem cells in vitro has not proved practical for routine transfusion. However, the perpetual and widespread shortage of blood products, problems related to transfusion-transmitted infections, and new emerging pathogens elicit an increasing demand for artificial blood. Worldwide efforts to achieve the goal of RBC production through stem cell research have received vast attention; however, problems with large-scale production and cost effectiveness have yet to prove practical usefulness. Some progress has been made, though, as cord blood stem cells and embryonic stem cells have shown an ability to differentiate and proliferate, and induced pluripotent stem cells have been shown to be an unlimited source for RBC production. However, transfusion of stem cell-derived RBCs still presents a number of challenges to overcome. This paper will summarize an up to date account of research and advances in stem cell-derived RBCs, delineate our laboratory protocol in producing RBCs from cord blood, and introduce the technological developments and limitations to current RBC production practices.

  18. Red blood cell: from its mechanics to its motion in shear flow.

    Science.gov (United States)

    Viallat, A; Abkarian, M

    2014-06-01

    There is a number of publications on red blood cell deformability, that is, on the remarkable cell ability to change its shape in response to an external force and to pass through the narrowest blood capillaries and splenic sinuses. Cell deformability is postulated to be a major determinant of impaired perfusion, increase of blood viscosity, and occlusion in microvessels. Current deformability tests like ektacytometry measure global parameters, related to shape changes at the whole cell scale. Despite strong advances in our understanding of the molecular organization of red blood cells, the relationships between the rheology of each element of the cell composite structure, the global deformability tests, and the cell behavior in microflows are still not elucidated. This review describes recent advances in the description of the dynamics of red blood cells in shear flow and in the mechanistic understanding of this dynamics at the scale of the constitutive rheological and structural elements of the cell. These developments could open up new horizons for the determination of red blood cell mechanical parameters by analyzing their motion under low shear flows.

  19. EFFECT OF ELECTROACUPUNCTURE ON RED BLOOD CELL IMMUNE AND T-CELL SUBGROUP IN THE RAT

    Institute of Scientific and Technical Information of China (English)

    高巍; 黄裕新; 陈洪; 孙大勇; 张洪新

    2000-01-01

    In the present study, the effect of electroacupuncture (EA) on immune system was observed in the rat by using micro- whole blood direct immunofluorescence Staining assay to detect changes of the peripheral blood T lymphocyte subgroup and employing red blood cell (RBC) C3b receptor- yeast rosette test and red blood cell-IC rosette test to analyze erythrocytic immune function. Resuits showed that after EA of “Zusanli” (ST 36), CD4+, RBC-C3bRR and RBC-ICR in the peripheral blood of the normal rats increased significantly while CDs+ had no any considerable changes and a positive correlation between CD~ and RBC-C3bRR was found. In immtttaosuppression model rats, the values of CD4+ and RBC-C3bRR were obviously lower than those of the normal control group while CD8+ had no any striking changes; but after EA treatment, there were no evident differences between EAgroup and normal control group in the above-mentioned indexes. There were also no any significant differences between non-acupoint group and normal control group in those indexes. Results suggest that EA of “Zusanli” (ST 36) can raise T cell immune function and RBC adhesion function in both normal rats and immunosuppression model rats, both of which present a positive correlation.

  20. EFFECT OF ELECTROACUPUNCTURE ON RED BLOOD CELL IMMUNE AND T-CELL SUBGROUP IN THE RAT

    Institute of Scientific and Technical Information of China (English)

    GaoWei; HuangYuxin; ChenHong; SunDayong; ZhangHongxin

    2000-01-01

    In the present study, the effect of electroacupuncture (EA) on immune system was observed in the rat by using micro- whole blood direct immunofluoreseence Staining assay to detect changes of the peripheral blood T lymphocyte subgroup and employing red blood cell (RBC) C3b receptor- yeast rosette test and red blood cell-IC rosette test to analyze erythroeytic immune function. Results showed that after EA of “Zusanli” (ST 36), CD4+, RBC-C3bRR and RBC-ICR in the peripheral blood of the normal rats increased significantly while CD8+ had no any considerable changes and a positive correlation between CD4+ and RBC-C3bRR was found. In immuoosuppression model rats, the values of CD4+ and RBC-C3bRR were obviously lower than those of the normal control group while CD8+ had no any striking changes; but after EA treatment, there were no evident differences between EA group and normal control group in the above-mentioned indexes. There were also no any significant differences between non-acupoint group and normal control group in those indexes. Results suggest that EA of “Zusanli” (ST 36) can raise T cell immune function and RBC adhesion function in both normal rats and immunosuppression model rats, both of which present a positive correlation.

  1. Fragmented red cells reference range (Sysmex XN(®) automated blood cell counter).

    Science.gov (United States)

    Lesesve, Jean-François; Daigney, Amandine; Henry, Sylvain; Speyer, Elodie

    2015-01-01

    Fragmented red cells (FRCs) is a new parameter automatedly determined by recent blood cell counters. Their count might be of interest because FRCs are supposed to reflect schistocytes counts measured on a stained peripheral blood smear observed under the microscope. But FRCs depend from the technical procedure used to detect them and thus reference ranges are device-dependent. The XN-9000(®) is one of the last model from Sysmex series. We aimed to establish reference range for FRCs, from 2389 controls. The mean ± SD was 0.32% ± 0.81, the median 0.02% (95% confidence interval ot the mean: 0.29-0.35%). We observed that the percentage of red blood cells with less than 17 pg of hemoglobin content (Hypo-He) was correlated to FRC increase, Hypo-He increase resulting in spurious FRCs majoration. FRCs reference range should be useful for: 1) laboratory staff in order to select which blood smears to check optically; 2) Sysmex company to set-up more optimal rules proposed with the counter (automated making of blood smear).

  2. Impact of red blood cell variants on childhood malaria in Mali: a prospective cohort study

    Science.gov (United States)

    Lopera-Mesa, Tatiana M; Doumbia, Saibou; Konaté, Drissa; Anderson, Jennifer M; Doumbouya, Mory; Keita, Abdoul S; Diakité, Seidina AS; Traoré, Karim; Krause, Michael A; Diouf, Ababacar; Moretz, Samuel E; STullo, Gregory; Miura, Kazutoyo; Gu, Wenjuan; Fay, Michael P; Taylor, Steve M; Long, Carole A; Diakité, Mahamadou; Fairhurst, Rick M

    2015-01-01

    Summary Background Red blood cell (RBC) variants protect African children from severe Plasmodium falciparum malaria. Their individual and interactive impacts on mild disease and parasite density, and their modification by age-dependent immunity, are poorly understood. Methods We conducted a 4-year, prospective cohort study of children aged 0.5–17 years in Maliin 2008-2011. Exposures were haemoglobin S (HbS), HbC, α-thalassaemia, ABO blood groups, and glucose-6-phosphate dehydrogenase (G6PD)deficiency encoded by the X-linked A- allele. Primary and secondary outcomes were malaria incidence and parasite density. Incidence rate ratios (IRRs) were modeled with quasi-Poisson regression; parasite densities were analyzed with Generalized Estimating Equations. Findings We diagnosed 4091 malaria episodes in 1543 children over 2656 child-years of follow-up (cyfu). RBC variants were common: HbAS 14.2%, HbAC 6.7%, α-thalassaemia 28.4%, type O blood group 40.2%, and G6PD deficiency9.4% (boys) and 20.4% (girls). Malaria incidence was 1.54 episodes/cyfu, ranged from 2.78 at age 3 to 0.40 at age 16 years, was reduced 34% in HbAS vs HbAA children (adjusted IRR [aIRR] 0.66; 95% CI 0.59-0.75) and 49% in G6PD A-/A- vs A+/A+ girls (aIRR 0.51; 95% CI 0.29-0.90), but was increased 15% in HbAC children (aIRR 1.15; 95% CI 1.01-1.32). Parasite density was reduced in HbAS vs HbAA children (median 10,550 vs 15, 150 parasites/μL; p=0.0004). HbAS-associated reductions in malaria risk and parasite density were greatest in early childhood. Interpretation Individual and interactive impacts of HbAS, HbAC, and G6PD A-/A-on malaria risk and parasite density define clinical and cellular correlates of protection. Further identification of the molecular mechanisms of these protective effects may uncover novel targets for intervention. Funding Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health. PMID:26687956

  3. Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus.

    Science.gov (United States)

    Cheng, Dong; Zhao, Jiangtao; Jian, Liguo; Ding, Tongbin; Liu, Shichao

    2016-09-01

    Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 ± 0.9 vs.12.5 ± 0.6, p red cell distribution width was positively associated with albuminuria creatinine ratio (r = 0.567, p red cell distribution width was still associated with early-stage renal injury after adjusting for many other potential cofounders. Compared with the first quartile, the risk ratio of the second, the third and the fourth quartile were 1.38 (95%CI: 1.06-1.80), 1.57 (95%CI: 1.21-2.97), 2.71 (95%CI: 2.08-3.54), respectively. Besides, systolic blood pressure, estimated glomerular filtration rate, uric acid and blood urea nitrogen were also significantly associated with renal injury in gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices.

  4. A Review of RedOx Cycling of Solid Oxide Fuel Cells Anode

    Directory of Open Access Journals (Sweden)

    Jan Van herle

    2012-08-01

    Full Text Available Solid oxide fuel cells are able to convert fuels, including hydrocarbons, to electricity with an unbeatable efficiency even for small systems. One of the main limitations for long-term utilization is the reduction-oxidation cycling (RedOx cycles of the nickel-based anodes. This paper will review the effects and parameters influencing RedOx cycles of the Ni-ceramic anode. Second, solutions for RedOx instability are reviewed in the patent and open scientific literature. The solutions are described from the point of view of the system, stack design, cell design, new materials and microstructure optimization. Finally, a brief synthesis on RedOx cycling of Ni-based anode supports for standard and optimized microstructures is depicted.

  5. Lidocaine action and conformational changes in cytoskeletal protein network in human red blood cells.

    Science.gov (United States)

    Nishiguchi, E; Hamada, N; Shindo, J

    1995-11-03

    The mechanism of action of lidocaine, which is commonly used clinically as a local anesthetic, was studied in human red blood cells. The influx of [14C]lidocaine through the cell membrane induced reversible transformation of human red blood cells from discocytes to stomatocytes. This change in shape depended on the lidocaine concentration and required both ATP and carbonic anhydrase. The lidocaine-induced shape change occurred as a result of spectrin aggregation, which altered the intracellular environment of the human red blood cells, mediated by carbonic anhydrase and activation of vacuolar type H(+)-ATPase (V-ATPase). Lidocaine controlled the influx of 22Na into the human red blood cells in a concentration-dependent manner. When incubated in media containing 6-chloro-9-[(4-diethylamino)-1-methyl-butyl]amino-2-methoxyacridine (mepacrine), an inhibitor of Na+ channels, human red blood cells changed shape from discocytes to stomatocytes and the intracellular pH decreased. This phenomenon was very similar to the shape change induced by lidocaine. These results suggest that the mode of action of lidocaine is related to a conformational change in the cytoskeletal protein network.

  6. Biochemical Storage Lesions Occurring in Nonirradiated and Irradiated Red Blood Cells: A Brief Review

    Directory of Open Access Journals (Sweden)

    F. Adams

    2015-01-01

    Full Text Available Red blood cells undergo a series of biochemical fluctuations during 35–42-day storage period at 1°C to 6°C. The sodium/potassium pump is immobilised causing a decrease in intracellular potassium with an increase in cytoplasmic sodium levels, glucose levels decline, and acidosis occurs as a result of low pH levels. The frailty of stored erythrocytes triggers the formation of haemoglobin-containing microparticles and the release of cell-free haemoglobin which may add to transfusion difficulties. Lipid peroxidation, oxidative stress to band 3 structures, and other morphological and structural molecular changes also occur leading to spheroechinocytes and osmotic fragility. These changes that transpire in the red cells during the storage period are referred to as “storage lesions.” It is well documented that gamma irradiation exacerbates storage lesions and the reports of increased potassium levels leading to adverse reactions observed in neonates and infants have been of particular concern. There are, however, remarkably few systematic studies comparing the in vitro storage lesions of irradiated and nonirradiated red cell concentrates and it has been suggested that the impact of storage lesions on leucocyte reduced red blood cell concentrate (RBCC is incomplete. The review examines storage lesions in red blood cells and their adverse effects in reference to blood transfusion.

  7. Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass

    Science.gov (United States)

    Rice, L.; Ruiz, W.; Driscoll, T.; Whitley, C. E.; Tapia, R.; Hachey, D. L.; Gonzales, G. F.; Alfrey, C. P.

    2001-01-01

    BACKGROUND: Studies of space-flight anemia have uncovered a physiologic process, neocytolysis, by which young red blood cells are selectively hemolyzed, allowing rapid adaptation when red cell mass is excessive for a new environment. OBJECTIVES: 1) To confirm that neocytolysis occurs in another situation of acute plethora-when high-altitude dwellers with polycythemia descend to sea level; and 2) to clarify the role of erythropoietin suppression. DESIGN: Prospective observational and interventional study. SETTING: Cerro de Pasco (4380 m) and Lima (sea level), Peru. PARTICIPANTS: Nine volunteers with polycythemia. INTERVENTIONS: Volunteers were transported to sea level; three received low-dose erythropoietin. MEASUREMENTS: Changes in red cell mass, hematocrit, hemoglobin concentration, reticulocyte count, ferritin level, serum erythropoietin, and enrichment of administered(13)C in heme. RESULTS: In six participants, red cell mass decreased by 7% to 10% within a few days of descent; this decrease was mirrored by a rapid increase in serum ferritin level. Reticulocyte production did not decrease, a finding that establishes a hemolytic mechanism.(13)C changes in circulating heme were consistent with hemolysis of young cells. Erythropoietin was suppressed, and administration of exogenous erythropoietin prevented the changes in red cell mass, serum ferritin level, and(13)C-heme. CONCLUSIONS: Neocytolysis and the role of erythropoietin are confirmed in persons with polycythemia who descend from high altitude. This may have implications that extend beyond space and altitude medicine to renal disease and other situations of erythropoietin suppression, hemolysis, and polycythemia.

  8. [Simplified preparation of test-red blood cells for ABO blood grouping in a laboratory in Madagascar].

    Science.gov (United States)

    Rasamiravaka, T; Andrianarivelo, A M; Ramarison, G; Rakoto-Alson, A O; Rasamindrakotroka, A

    2011-10-01

    To ensure self-sufficiency and lower costs associated with reagent red blood cells, some medical laboratories produce their own test-red blood cells for plasma ABO blood grouping. However, given the vital importance of blood goup testing, it is essential to verify the reliability of these cells. The purpose of this study was to assess the quality of laboratory-made ABO test-red blood cells. This study comparing house made and commercially available test-red blood cells was carried out at the Medical Biology Training and Research Laboratory in Madagascar. This laboratory is attended by people wishing to obtain their blood group card. In this population, no discrepancy was found between the red cell and plasma tests. Comparison of test-red blood cells with commercially available reagent red blood cells showed no difference in reactivity in the first four days of conservation. However a decrease in the reactivity of house made cells appeared on the 5th day. House made red blood cells are costless than commercially available reagent red blood cells mainly due to the simplified method of preparation. However, since laboratory-made cells progressivley lose antigenic reactivity quicly, production must be repeated regularly and good internal quality control is necessary to ensure reliability.

  9. Ion channels in human red blood cell membrane: actors or relics?

    Science.gov (United States)

    Thomas, Serge L Y; Bouyer, Guillaume; Cueff, Anne; Egée, Stéphane; Glogowska, Edyta; Ollivaux, Céline

    2011-04-15

    During the past three decades, electrophysiological studies revealed that human red blood cell membrane is endowed with a large variety of ion channels. The physiological role of these channels, if any, remains unclear; they do not participate in red cell homeostasis which is rather based on the almost total absence of cationic permeability and minute anionic conductance. They seem to be inactive in the "resting cell." However, when activated experimentally, ion channels can lead to a very high single cell conductance and potentially induce disorders, with the major risks of fast dehydration and dissipation of gradients. Could there be physiological conditions under which the red cell needs to activate these high conductances, or are ion channels relics of a function lost in anucleated cells? It has been demonstrated that they play a key role in diseases such as sickle cell anemia or malaria. This short overview of ion channels identified to-date in the human red cell membrane is an attempt to propose a dynamic role for these channels in circulating cells in health and disease.

  10. Red oil A5 inhibits proliferation and induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Mi-Lian Dong; Xian-Zhong Ding; Thomas E. Adrian

    2004-01-01

    AIM: To study the effect of red oil A5 on pancreatic cancer cells and its possible mechanisms.METHODS: Effect of different concentrations of red oil A5on proliferation of three pancreatic cancer cell lines, AsPC-1,MiaPaCa-2 and S2013, was measured by 3H-methyl thymidine incorporation. Time-dependent effects of 1:32 000 red oil A5 on proliferation of three pancreatic cancer cell lines, were also measured by 3H-methyl thymidine incorporation, and Time-course effects of 1:32 000 red oil A5 on cell number.The cells were counted by Z1-Coulter Counter. Fiowcytometric analysis of cellular DNA content in the control and red oil A5 treated AsPC-1, MiaPaCa-2 and S2013 cells,were stained with propidium iodide. TUNEL assay of red oil A5-induced pancreatic cancer cell apoptosis was performed.Western blotting of the cytochrome c protein in AsPC-1,MiaPaCa-2 and S2013 cells treated 24 hours with 1:32 000red oil A5 was performed. Proteins in cytosolic fraction and in mitochondria fraction were extracted. Proteins extracted from each sample were electrophoresed on SDS-PAGE gels and then were transferred to nitrocellulose membranes.Cytochrome c was identified using a monoclonal cytochrome c antibody. Western blotting of the caspase-3 protein in AsPC-1, MliaPaCa-2 and S2013 cells treated with 1:32 000 red oil A5 for 24 hours was carried out. Proteins in whole cellular lysates were electrophoresed on SDS-PAGE gels and then transferred to nitrocellulose membranes. Caspase-3 was identified using a specific antibody. Western blotting of polyADP ribose polymerase (PARP) protein in AsPC-1, MiaPaCa2 and S2013 cells treated with 1:32 000 red oil A5 for 24 hours was performed. Proteins in whole cellular lysates were separated by electrophoresis on SDS-PAGE gels and then transferred to nitrocellulose membranes. PARP was identified by using a monoclonal antibody.RESULTS: Red oil A5 caused dose- and time-dependent inhibition of pancreatic cancer cell proliferation. Propidium iodide DNA staining

  11. Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function

    Science.gov (United States)

    Kanias, Tamir; Triulzi, Darrel; Donadee, Chenell; Barge, Suchitra; Badlam, Jessica; Jain, Shilpa; Belanger, Andrea M.; Kim-Shapiro, Daniel B.

    2015-01-01

    Rationale: A major abnormality that characterizes the red cell “storage lesion” is increased hemolysis and reduced red cell lifespan after infusion. Low levels of intravascular hemolysis after transfusion of aged stored red cells disrupt nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell-free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion and effects on endothelial-dependent vasodilation responses to acetylcholine have not been fully characterized in humans. Objectives: To evaluate the effects of blood aged to the limits of Food and Drug Administration–approved storage time on the human microcirculation and endothelial function. Methods: Eighteen healthy individuals donated 1 U of leukopheresed red cells, divided and autologously transfused into the forearm brachial artery 5 and 42 days after blood donation. Blood samples were obtained from stored blood bag supernatants and the antecubital vein of the infusion arm. Forearm blood flow measurements were performed using strain-gauge plethysmography during transfusion, followed by testing of endothelium-dependent blood flow with increasing doses of intraarterial acetylcholine. Measurements and Main Results: We demonstrate that aged stored blood has higher levels of arginase-1 and cell-free plasma hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells decreases acetylcholine-dependent forearm blood flows. Intravascular venous levels of arginase-1 and cell-free plasma hemoglobin increase immediately after red cell transfusion, with more significant increases observed after infusion of 42-day-old blood. Conclusions: We demonstrate that the transfusion of blood at the limits of Food and Drug Administration–approved storage has a significant effect on the forearm circulation and impairs endothelial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01137656) PMID:26222884

  12. Production of embryonic and fetal-like red blood cells from human induced pluripotent stem cells.

    Science.gov (United States)

    Chang, Chan-Jung; Mitra, Koyel; Koya, Mariko; Velho, Michelle; Desprat, Romain; Lenz, Jack; Bouhassira, Eric E

    2011-01-01

    We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications.

  13. Production of embryonic and fetal-like red blood cells from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Chan-Jung Chang

    Full Text Available We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications.

  14. Red blood cell cluster separation from digital images for use in sickle cell disease.

    Science.gov (United States)

    González-Hidalgo, Manuel; Guerrero-Peña, F A; Herold-García, S; Jaume-I-Capó, Antoni; Marrero-Fernández, P D

    2015-07-01

    The study of cell morphology is an important aspect of the diagnosis of some diseases, such as sickle cell disease, because red blood cell deformation is caused by these diseases. Due to the elongated shape of the erythrocyte, ellipse adjustment and concave point detection are applied widely to images of peripheral blood samples, including during the detection of cells that are partially occluded in the clusters generated by the sample preparation process. In the present study, we propose a method for the analysis of the shape of erythrocytes in peripheral blood smear samples of sickle cell disease, which uses ellipse adjustments and a new algorithm for detecting notable points. Furthermore, we apply a set of constraints that allow the elimination of significant image preprocessing steps proposed in previous studies. We used three types of images to validate our method: artificial images, which were automatically generated in a random manner using a computer code; real images from peripheral blood smear sample images that contained normal and elongated erythrocytes; and synthetic images generated from real isolated cells. Using the proposed method, the efficiency of detecting the two types of objects in the three image types exceeded 99.00%, 98.00%, and 99.35%, respectively. These efficiency levels were superior to the results obtained with previously proposed methods using the same database, which is available at http://erythrocytesidb.uib.es/. This method can be extended to clusters of several cells and it requires no user inputs.

  15. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells.

    Science.gov (United States)

    Katz, Samuel G; Labelle, James L; Meng, Hailong; Valeriano, Regina P; Fisher, Jill K; Sun, Heather; Rodig, Scott J; Kleinstein, Steven H; Walensky, Loren D

    2014-02-06

    Mantle cell lymphoma (MCL) is a highly aggressive B-cell lymphoma resistant to conventional chemotherapy. Although defined by the characteristic t(11;14) translocation, MCL has not been recapitulated in transgenic mouse models of cyclin D1 overexpression alone. Indeed, several genetic aberrations have been identified in MCL that may contribute to its pathogenesis and chemoresistance. Of particular interest is the frequent biallelic deletion of the proapoptotic BCL-2 family protein BIM. BIM exerts its pro-death function via its α-helical BH3 death domain that has the dual capacity to inhibit antiapoptotic proteins such as BCL-2 and MCL-1 and directly trigger proapoptotic proteins such as the mitochondrial executioner protein BAX. To evaluate a functional role for Bim deletion in the pathogenesis of MCL, we generated cyclin D1-transgenic mice harboring Bim-deficient B cells. In response to immunization, Eμ(CycD1)CD19(CRE)Bim(fl/fl) mice manifested selective expansion of their splenic mantle zone compartment. Three distinct immune stimulation regimens induced lymphomas with histopathologic and molecular features of human MCL in a subset of mice. Thus, deletion of Bim in B cells, in the context of cyclin D1 overexpression, disrupts a critical control point in lymphoid maturation and predisposes to the development of MCL. This genetic proof of concept for MCL pathogenesis suggests an opportunity to reactivate the death pathway by pharmacologic mimicry of proapoptotic BIM.

  16. Vitamin D Deficiency Reduces the Immune Response, Phagocytosis Rate, and Intracellular Killing Rate of Microglial Cells

    Science.gov (United States)

    Onken, Marie Luise; Schütze, Sandra; Redlich, Sandra; Götz, Alexander; Hanisch, Uwe-Karsten; Bertsch, Thomas; Ribes, Sandra; Hanenberg, Andrea; Schneider, Simon; Bollheimer, Cornelius; Sieber, Cornel; Nau, Roland

    2014-01-01

    Meningitis and meningoencephalitis caused by Escherichia coli are associated with high rates of mortality and neurological sequelae. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. Vitamin D has potent effects on human immunity, including induction of antimicrobial peptides (AMPs) and suppression of T-cell proliferation, but its influence on microglial cells is unknown. The purpose of the present study was to determine the effects of vitamin D deficiency on the phagocytosis rate, intracellular killing, and immune response of murine microglial cultures after stimulation with the Toll-like receptor (TLR) agonists tripalmitoyl-S-glyceryl-cysteine (TLR1/2), poly(I·C) (TLR3), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9). Upon stimulation with high concentrations of TLR agonists, the release of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was decreased in vitamin D-deficient compared to that in vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1 after stimulation of microglial cells with high concentrations of TLR3, -4, and -9 agonists and intracellular killing of E. coli K1 after stimulation with high concentrations of all TLR agonists were lower in vitamin D-deficient microglial cells than in the respective control cells. Our observations suggest that vitamin D deficiency may impair the resistance of the brain against bacterial infections. PMID:24686054

  17. Prion Protein Deficiency Causes Diverse Proteome Shifts in Cell Models That Escape Detection in Brain Tissue.

    Directory of Open Access Journals (Sweden)

    Mohadeseh Mehrabian

    Full Text Available A popular method for studying the function of a given protein is to generate and characterize a suitable model deficient for its expression. For the prion protein (PrP, best known for its role in several invariably fatal neurodegenerative diseases, a natural choice, therefore, would be to undertake such studies with brain samples. We recently documented the surprising observation that PrP deficiency caused a loss or enhancement of NCAM1 polysialylation, dependent on the cell model used. To identify possible causes for this disparity, we set out to systematically investigate the consequence of PrP deficiency on the global proteome in brain tissue and in four distinct cell models. Here we report that PrP deficiency causes robust but surprisingly divergent changes to the global proteomes of cell models but has no discernible impact on the global brain proteome. Amongst >1,500 proteins whose levels were compared in wild-type and PrP-deficient models, members of the MARCKS protein family exhibited pronounced, yet cell model-dependent changes to their steady-state levels. Follow-up experiments revealed that PrP collaborates with members of the MARCKS protein family in its control of NCAM1 polysialylation. We conclude that the physiological function of PrP may be masked in analyses of complex brain samples but its cell-type specific influence on a lipid raft-based NCAM1-related cell biology comes to the fore in investigations of specific cell types.

  18. Numerical simulation of red blood cell suspensions behind a moving interface in a capillary

    CERN Document Server

    Zhao, Shihai

    2013-01-01

    Computational modeling and simulation are presented on the motion of red blood cells behind a moving interface in a capillary. The methodology is based on an immersed boundary method and the skeleton structure of the red blood cell (RBC) membrane is modeled as a spring network. The computational domain is moving with either a designated RBC or an interface in an infinitely long two-dimensional channel with an undisturbed flow field in front of the domain. The tanking-treading and the inclination angle of a cell in a simple shear flow are briefly discussed for the validation purpose. We then present the results of the motion of red blood cells behind a moving interface in a capillary, which show that the RBCs with higher velocity than the interface speed form a concentrated slug behind the interface.

  19. Coarse-Grained Molecular Dynamics Simulation of a Red Blood Cell

    Science.gov (United States)

    Jiang, Li-Guo; Wu, Heng-An; Zhou, Xiao-Zhou; Wang, Xiu-Xi

    2010-02-01

    A worm-like chain model based on a spectrin network is employed to study the biomechanics of red blood cells. Coarse-grained molecular dynamics simulations are performed to obtain a stable configuration free of external loadings. We also discuss the influence of two parameters: the average bending modulus and the persistence length. The change in shape of a malaria-infected red blood cell can contribute to the change in its molecular-based structure. As the persistence length of the membrane network in the infected red blood cell decreases, the deformability decreases and the biconcave shape is destroyed. The numerical results are comparable with previously reported experimental results. The coarse-grained model can be used to study the relationship between macro-mechanical properties and molecular-scale structures of cells.

  20. GPU-accelerated Red Blood Cells Simulations with Transport Dissipative Particle Dynamics

    CERN Document Server

    Blumers, Ansel L; Li, Zhen; Li, Xuejin; Karniadakis, George E

    2016-01-01

    Mesoscopic numerical simulations provide a unique approach for the quantification of the chemical influences on red blood cell functionalities. The transport Dissipative Particles Dynamics (tDPD) method can lead to such effective multiscale simulations due to its ability to simultaneously capture mesoscopic advection, diffusion, and reaction. In this paper, we present a GPU-accelerated red blood cell simulation package based on a tDPD adaptation of our red blood cell model, which can correctly recover the cell membrane viscosity, elasticity, bending stiffness, and cross-membrane chemical transport. The package essentially processes all computational workloads in parallel by GPU, and it incorporates multi-stream scheduling and non-blocking MPI communications to improve inter-node scalability. Our code is validated for accuracy and compared against the CPU counterpart for speed. Strong scaling and weak scaling are also presented to characterizes scalability. We observe a speedup of 10.1 on one GPU over all 16 c...

  1. Non-tuberculous Mycobacteriosis with T-cell Lymphoma in a Red Panda (Ailurus fulgens).

    Science.gov (United States)

    Fuke, N; Hirai, T; Makimura, N; Goto, Y; Habibi, W A; Ito, S; Trang, N T; Koshino, K; Takeda, M; Yamaguchi, R

    2016-01-01

    A 9-year-old male red panda (Ailurus fulgens) became emaciated and died. Necropsy examination revealed systemic lymphadenomegaly. The liver, lungs and left kidney contained multifocal yellow nodules. Microscopical examination revealed granulomatous inflammation in the liver, lungs, kidney, spleen and lymph nodes, with numerous acid-fast bacilli. Sequencing of genetic material isolated from the tissues classified the pathogen as Mycobacterium gastri. Lymphoma was found in the liver, lungs, kidney and lymph nodes. The neoplastic cells were strongly labelled for expression of CD3, Ki67 and proliferating cell nuclear antigen by immunohistochemistry. This is the first report of M. gastri infection with T-cell lymphoma in a red panda.

  2. Theoretical and experimental study of electroporation of red blood cells using MEMS technology

    KAUST Repository

    Deng, Peigang

    2010-01-01

    A theoretical and experimental study of electroporation (EP) of red blood cells (RBCs) was presented in this paper. With additional strain energy, an energy-based model of an electropore induced on a RBC\\'s membrane at different electric fields was proposed to predict the critical EP electric field strength. In addition, EP experiments with red blood cells at single-cell level was carried out on a micro EP chip. The measured critical EP electric field strengths are in agreement with the numerical predictions. ©2010 IEEE.

  3. Morphological and biochemical characterization of mitochondria in Torpedo red blood cells.

    Science.gov (United States)

    Pica, A; Scacco, S; Papa, F; De Nitto, E; Papa, S

    2001-02-01

    A study is presented on the morphology and respiratory functions of mitochondria from Torpedo marmorata red blood cells. In vivo staining of red blood cells and transmission electron microscopy showed the existence of a considerable number of vital and orthodox mitochondria which decreased from young erythroblasts to mature erythrocytes from 60-50 to 30-20 per cell. In erythrocytes mitochondria exhibited a canonical, functional respiratory chain. The content and activity of cytochromes in erythrocytes were, however, significantly lower as compared to mammalian tissues.

  4. Mixing processes during the evolution of red giants with moderate metal deficiencies the role of molecular-weight barriers

    CERN Document Server

    Charbonnel, C; Wallerstein, G; Charbonnel, Corinne; Brown, Jeffery A.; Wallerstein, George

    1997-01-01

    We have assembled accurate abundance data for Li, C, and N as well as the 12C/13C ratio for five field giants with [Fe/H]=-0.6 including Arcturus and two stars in the globular cluster 47 Tuc. Using their very precise Mbol values obtained from HIPPARCOSparallaxes, we can place them into an evolutionary sequence. The sequence shows that the 12C/13C ratios ratios drops from 20 to near 7 between Mbol=+1 and +0.5, while Li disappears. At the same time the 12C/14N ratio diminishes by 0.2 to 0.4 dex. The two stars in 47 Tuc with Mbol near -2.0 show even lower 12C14N ratios by 0.4 dex indicating further mixing as they evolved to the top of the red giant branch. These observations confirm the existence of an extra-mixing process that becomes efficient on the red giant branch only when the low-mass stars reach the so-called luminosity function bump. We use the values of the carbon isotopic ratio observed in our sample to get constraints on the mu-barriers that may shield the central regions of a star from extra-mixing....

  5. Enzymes and membrane proteins of ADSOL-preserved red blood cells

    Directory of Open Access Journals (Sweden)

    Maria Sueli Soares Leonart

    2000-03-01

    Full Text Available CONTEXT: The preservative solution ADSOL (adenine, dextrose, sorbitol, sodium chloride and mannitol maintains red cell viability for blood trans-fusion for 6 weeks. It would be useful to know about its preservation qualities over longer periods. OBJECTIVE: To determine some red cell biochemical parameters for peri-ods of up to 14 weeks in order to determine whether the red cell metabo-lism integrity would justify further studies aiming at increasing red cell preservation and viability. DESIGN: Biochemical evaluation designed to study red cell preservation. SETTING: São Paulo University erythrocyte metabolism referral center. SAMPLE: Six normal blood donors from the University Hospital of the Universidade Federal do Paraná, Curitiba, Brazil. MAIN MEASUREMENTS: Weekly assay of erythrocyte adenosine-5´-triphosphate (ATP, 2,3-diphosphoglycerate (2,3DPG, hexokinase (HX, phosphofructokinase (PFK, pyruvate kinase (PK, glucose-6-phosphate dehydrogenase (G-6-PD, 6-phosphogluconic dehydrogenase (6-PGD, glyceraldehyde-3-phosphate dehydrogenase (GAPD, glutathione reduc-tase (GR, glutathione peroxidase (GSHPx, plasma sodium and potas-sium, blood pH, and membrane proteins of red cells preserved in ADSOL were studied during storage for 14 weeks storage. RESULTS: During ADSOL preservation, erythrocyte ATP concentration decreased 60% after 5 weeks, and 90% after 10 weeks; the pH fell from 6.8 to 6.4 by the 14th week. 2,3-DPG concentration was stable during the first week, but fell 90% after 3 weeks and was exhausted after 5 weeks. By the end of the 5th week, an activity decrease of 16-30% for Hx, GAPD, GR, G-6-PD and 6-PGD, 35% for PFK and GSHPx, and 45% for PK were observed. Thereafter, a uniform 10% decay was observed for all enzymes up to the 14th week. The red blood cell membrane pro-teins did not show significant alterations in polyacrylamide gel electro-phoresis (SDS-PAGE during the 14 weeks. CONCLUSION: Although the blood viability was shown to be poor

  6. Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Taubenheim, Nadine; Peron, Sophie; Fischer, Alain

    2007-01-01

    B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly established the role of AID in the induction of the Ig gene rearrangements underlying CSR and SHM. A CSR-specific function of AID has, however, been detected by the observation of a selective CSR defect caused by mutations affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil-N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision repair machinery, removes uracils from DNA and AID deaminates cytosines into uracils, that observation indicates that the AID-UNG pathway directly targets DNA of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR deficiencies 3 and 4 are characterized by a selective CSR defect resulting from blocks at distinct steps of CSR. A further understanding of the CSR machinery is expected from their molecular definition.

  7. Analysis of Hereditary Elliptocytosis with Decreased Binding of Eosin-5-maleimide to Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Suemori

    2015-01-01

    Full Text Available Flow cytometric test for analyzing the eosin-5-maleimide (EMA binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS. However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP and Southeast Asian ovalocytosis (SAO, which are forms in the category of hereditary elliptocytosis (HE, show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF cut-off value of 36.4 (sensitivity 0.97, specificity 0.95. Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells.

  8. Seventy-five genetic loci influencing the human red blood cell

    Science.gov (United States)

    van der Harst, Pim; Zhang, Weihua; Leach, Irene Mateo; Rendon, Augusto; Verweij, Niek; Sehmi, Joban; Paul, Dirk S.; Elling, Ulrich; Allayee, Hooman; Li, Xinzhong; Radhakrishnan, Aparna; Tan, Sian-Tsung; Voss, Katrin; Weichenberger, Christian X.; Albers, Cornelis A.; Al-Hussani, Abtehale; Asselbergs, Folkert W.; Ciullo, Marina; Danjou, Fabrice; Dina, Christian; Esko, Tõnu; Evans, David M.; Franke, Lude; Gögele, Martin; Hartiala, Jaana; Hersch, Micha; Holm, Hilma; Hottenga, Jouke-Jan; Kanoni, Stavroula; Kleber, Marcus E.; Lagou, Vasiliki; Langenberg, Claudia; Lopez, Lorna M.; Lyytikäinen, Leo-Pekka; Melander, Olle; Murgia, Federico; Nolte, Ilja M.; O’Reilly, Paul F.; Padmanabhan, Sandosh; Parsa, Afshin; Pirastu, Nicola; Porcu, Eleonora; Portas, Laura; Prokopenko, Inga; Ried, Janina S.; Shin, So-Youn; Tang, Clara S.; Teumer, Alexander; Traglia, Michela; Ulivi, Sheila; Westra, Harm-Jan; Yang, Jian; Zhao, Jing Hua; Anni, Franco; Abdellaoui, Abdel; Attwood, Antony; Balkau, Beverley; Bandinelli, Stefania; Bastardot, François; Benyamin, Beben; Boehm, Bernhard O.; Cookson, William O.; Das, Debashish; de Bakker, Paul I. W.; de Boer, Rudolf A.; de Geus, Eco J. C.; de Moor, Marleen H.; Dimitriou, Maria; Domingues, Francisco S.; Döring, Angela; Engström, Gunnar; Eyjolfsson, Gudmundur Ingi; Ferrucci, Luigi; Fischer, Krista; Galanello, Renzo; Garner, Stephen F.; Genser, Bernd; Gibson, Quince D.; Girotto, Giorgia; Gudbjartsson, Daniel Fannar; Harris, Sarah E.; Hartikainen, Anna-Liisa; Hastie, Claire E.; Hedblad, Bo; Illig, Thomas; Jolley, Jennifer; Kähönen, Mika; Kema, Ido P.; Kemp, John P.; Liang, Liming; Lloyd-Jones, Heather; Loos, Ruth J. F.; Meacham, Stuart; Medland, Sarah E.; Meisinger, Christa; Memari, Yasin; Mihailov, Evelin; Miller, Kathy; Moffatt, Miriam F.; Nauck, Matthias; Novatchkova, Maria; Nutile, Teresa; Olafsson, Isleifur; Onundarson, Pall T.; Parracciani, Debora; Penninx, Brenda W.; Perseu, Lucia; Piga, Antonio; Pistis, Giorgio; Pouta, Anneli; Puc, Ursula; Raitakari, Olli; Ring, Susan M.; Robino, Antonietta; Ruggiero, Daniela; Ruokonen, Aimo; Saint-Pierre, Aude; Sala, Cinzia; Salumets, Andres; Sambrook, Jennifer; Schepers, Hein; Schmidt, Carsten Oliver; Silljé, Herman H. W.; Sladek, Rob; Smit, Johannes H.; Starr, John M.; Stephens, Jonathan; Sulem, Patrick; Tanaka, Toshiko; Thorsteinsdottir, Unnur; Tragante, Vinicius; van Gilst, Wiek H.; van Pelt, L. Joost; van Veldhuisen, Dirk J.; Völker, Uwe; Whitfield, John B.; Willemsen, Gonneke; Winkelmann, Bernhard R.; Wirnsberger, Gerald; Algra, Ale; Cucca, Francesco; d’Adamo, Adamo Pio; Danesh, John; Deary, Ian J.; Dominiczak, Anna F.; Elliott, Paul; Fortina, Paolo; Froguel, Philippe; Gasparini, Paolo; Greinacher, Andreas; Hazen, Stanley L.; Jarvelin, Marjo-Riitta; Khaw, Kay Tee; Lehtimäki, Terho; Maerz, Winfried; Martin, Nicholas G.; Metspalu, Andres; Mitchell, Braxton D.; Montgomery, Grant W.; Moore, Carmel; Navis, Gerjan; Pirastu, Mario; Pramstaller, Peter P.; Ramirez-Solis, Ramiro; Schadt, Eric; Scott, James; Shuldiner, Alan R.; Smith, George Davey; Smith, J. Gustav; Snieder, Harold; Sorice, Rossella; Spector, Tim D.; Stefansson, Kari; Stumvoll, Michael; Wilson Tang, W. H.; Toniolo, Daniela; Tönjes, Anke; Visscher, Peter M.; Vollenweider, Peter; Wareham, Nicholas J.; Wolffenbuttel, Bruce H. R.; Boomsma, Dorret I.; Beckmann, Jacques S.; Dedoussis, George V.; Deloukas, Panos; Ferreira, Manuel A.; Sanna, Serena; Uda, Manuela; Hicks, Andrew A.; Penninger, Josef Martin; Gieger, Christian; Kooner, Jaspal S.; Ouwehand, Willem H.; Soranzo, Nicole; Chambers, John C

    2013-01-01

    Anaemia is a chief determinant of globalill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P <10−8, which together explain 4–9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function. PMID:23222517

  9. Analysis of Hereditary Elliptocytosis with Decreased Binding of Eosin-5-maleimide to Red Blood Cells.

    Science.gov (United States)

    Suemori, Shin-ichiro; Wada, Hideho; Nakanishi, Hidekazu; Tsujioka, Takayuki; Sugihara, Takashi; Tohyama, Kaoru

    2015-01-01

    Flow cytometric test for analyzing the eosin-5-maleimide (EMA) binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS). However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP) and Southeast Asian ovalocytosis (SAO), which are forms in the category of hereditary elliptocytosis (HE), show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF) cut-off value of 36.4 (sensitivity 0.97, specificity 0.95). Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells.

  10. Seventy-five genetic loci influencing the human red blood cell.

    Science.gov (United States)

    van der Harst, Pim; Zhang, Weihua; Mateo Leach, Irene; Rendon, Augusto; Verweij, Niek; Sehmi, Joban; Paul, Dirk S; Elling, Ulrich; Allayee, Hooman; Li, Xinzhong; Radhakrishnan, Aparna; Tan, Sian-Tsung; Voss, Katrin; Weichenberger, Christian X; Albers, Cornelis A; Al-Hussani, Abtehale; Asselbergs, Folkert W; Ciullo, Marina; Danjou, Fabrice; Dina, Christian; Esko, Tõnu; Evans, David M; Franke, Lude; Gögele, Martin; Hartiala, Jaana; Hersch, Micha; Holm, Hilma; Hottenga, Jouke-Jan; Kanoni, Stavroula; Kleber, Marcus E; Lagou, Vasiliki; Langenberg, Claudia; Lopez, Lorna M; Lyytikäinen, Leo-Pekka; Melander, Olle; Murgia, Federico; Nolte, Ilja M; O'Reilly, Paul F; Padmanabhan, Sandosh; Parsa, Afshin; Pirastu, Nicola; Porcu, Eleonora; Portas, Laura; Prokopenko, Inga; Ried, Janina S; Shin, So-Youn; Tang, Clara S; Teumer, Alexander; Traglia, Michela; Ulivi, Sheila; Westra, Harm-Jan; Yang, Jian; Zhao, Jing Hua; Anni, Franco; Abdellaoui, Abdel; Attwood, Antony; Balkau, Beverley; Bandinelli, Stefania; Bastardot, François; Benyamin, Beben; Boehm, Bernhard O; Cookson, William O; Das, Debashish; de Bakker, Paul I W; de Boer, Rudolf A; de Geus, Eco J C; de Moor, Marleen H; Dimitriou, Maria; Domingues, Francisco S; Döring, Angela; Engström, Gunnar; Eyjolfsson, Gudmundur Ingi; Ferrucci, Luigi; Fischer, Krista; Galanello, Renzo; Garner, Stephen F; Genser, Bernd; Gibson, Quince D; Girotto, Giorgia; Gudbjartsson, Daniel Fannar; Harris, Sarah E; Hartikainen, Anna-Liisa; Hastie, Claire E; Hedblad, Bo; Illig, Thomas; Jolley, Jennifer; Kähönen, Mika; Kema, Ido P; Kemp, John P; Liang, Liming; Lloyd-Jones, Heather; Loos, Ruth J F; Meacham, Stuart; Medland, Sarah E; Meisinger, Christa; Memari, Yasin; Mihailov, Evelin; Miller, Kathy; Moffatt, Miriam F; Nauck, Matthias; Novatchkova, Maria; Nutile, Teresa; Olafsson, Isleifur; Onundarson, Pall T; Parracciani, Debora; Penninx, Brenda W; Perseu, Lucia; Piga, Antonio; Pistis, Giorgio; Pouta, Anneli; Puc, Ursula; Raitakari, Olli; Ring, Susan M; Robino, Antonietta; Ruggiero, Daniela; Ruokonen, Aimo; Saint-Pierre, Aude; Sala, Cinzia; Salumets, Andres; Sambrook, Jennifer; Schepers, Hein; Schmidt, Carsten Oliver; Silljé, Herman H W; Sladek, Rob; Smit, Johannes H; Starr, John M; Stephens, Jonathan; Sulem, Patrick; Tanaka, Toshiko; Thorsteinsdottir, Unnur; Tragante, Vinicius; van Gilst, Wiek H; van Pelt, L Joost; van Veldhuisen, Dirk J; Völker, Uwe; Whitfield, John B; Willemsen, Gonneke; Winkelmann, Bernhard R; Wirnsberger, Gerald; Algra, Ale; Cucca, Francesco; d'Adamo, Adamo Pio; Danesh, John; Deary, Ian J; Dominiczak, Anna F; Elliott, Paul; Fortina, Paolo; Froguel, Philippe; Gasparini, Paolo; Greinacher, Andreas; Hazen, Stanley L; Jarvelin, Marjo-Riitta; Khaw, Kay Tee; Lehtimäki, Terho; Maerz, Winfried; Martin, Nicholas G; Metspalu, Andres; Mitchell, Braxton D; Montgomery, Grant W; Moore, Carmel; Navis, Gerjan; Pirastu, Mario; Pramstaller, Peter P; Ramirez-Solis, Ramiro; Schadt, Eric; Scott, James; Shuldiner, Alan R; Smith, George Davey; Smith, J Gustav; Snieder, Harold; Sorice, Rossella; Spector, Tim D; Stefansson, Kari; Stumvoll, Michael; Tang, W H Wilson; Toniolo, Daniela; Tönjes, Anke; Visscher, Peter M; Vollenweider, Peter; Wareham, Nicholas J; Wolffenbuttel, Bruce H R; Boomsma, Dorret I; Beckmann, Jacques S; Dedoussis, George V; Deloukas, Panos; Ferreira, Manuel A; Sanna, Serena; Uda, Manuela; Hicks, Andrew A; Penninger, Josef Martin; Gieger, Christian; Kooner, Jaspal S; Ouwehand, Willem H; Soranzo, Nicole; Chambers, John C

    2012-12-20

    Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

  11. Low red blood cell levels of deglycating enzymes incolorectal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Maria Notarnicola; Maria Gabriella Caruso; Valeria Tutino; Vito Guerra; Giovanni Misciagna

    2011-01-01

    AIM: To investigate Glyoxalase Ⅰ and fructosamine-3- kinase (FN3K) activity in red blood cells from patients with colorectal adenomas and cancer.METHODS: Thirty three consecutive subjects with one or more histologically confirmed colorectal adenomatous polyps, 16 colorectal cancer patients and a group of 11 control subjects with normal colonoscopy were included in the study. Glyoxalase Ⅰ and FN3K activities were measured in red blood cells using a spectrophotometric and radiometric assay, respectively.RESULTS: A significant reduction in both Glyoxalase Ⅰ and FN3K activity was detected in patients with tumors compared to patients with adenomas and the controls. Erythrocyte Glyoxalase Ⅰ activity in colorectal cancer was approximately 6 times lower than that detected in patients with adenoma (0.022 ± 0.01 mmol/min per milliliter vs 0.128 ± 0.19 mmol/min per milliliter of red blood cells, P = 0.003, Tukey's test). FN3K activity in red blood cells from patients with colon cancer was approximately 2 times lower than that detected in adenomapatients (19.55 ± 6.4 pmol/min per milliliter vs 38.6 ± 31.7 pmol/min per milliliter of red blood cells, P = 0.04, Tukey's test).CONCLUSION: These findings suggest that deglycating enzymes may be involved in the malignant transformation of colon mucosa.

  12. Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis.

    Science.gov (United States)

    van Zwieten, Rob; van Oirschot, Brigitte A; Veldthuis, Martijn; Dobbe, Johannes G; Streekstra, Geert J; van Solinge, Wouter W; Schutgens, Roger E G; van Wijk, Richard

    2015-03-01

    In a family with mild dominant spherocytosis, affected members showed partial band 3 deficiency. The index patient showed more severe clinical symptoms than his relatives, and his red blood cells displayed concomitant low pyruvate kinase activity. We investigated the contribution of partial PK deficiency to the phenotypic expression of mutant band 3 in this family. Pyruvate kinase deficiency and band 3 deficiency were characterized by DNA analysis. Results of red cell osmotic fragility testing, the results of cell deformability obtained by the Automated Rheoscope and Cell Analyzer and the results obtained by Osmotic Gradient Ektacytometry, which is a combination of these tests, were related to the red cell ATP content. Spherocytosis in this family was due to a novel heterozygous mutation in SLC4A1, the gene for band 3. Reduced PK activity of the index patient was attributed to a novel mutation in PKLR inherited from his mother, who was without clinical symptoms. Partial PK deficiency was associated with decreased red cell ATP content and markedly increased osmotic fragility. This suggests an aggravating effect of low ATP levels on the phenotypic expression of band 3 deficiency.

  13. ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency

    Science.gov (United States)

    Mohni, Kareem N.; Kavanaugh, Gina M.; Cortez, David

    2014-01-01

    The DNA damage response kinase ATR and its effector kinase CHEK1 are required for cancer cells to survive oncogene-induced replication stress. ATR inhibitors exhibit synthetic lethal interactions with deficiencies in the DNA damage response enzymes ATM and XRCC1 and with overexpression of the cell cycle kinase Cyclin E. Here we report a systematic screen to identify synthetic lethal interactions with ATR-pathway targeted drugs, rationalized by their predicted therapeutic utility in the oncology clinic. We found that reduced function in the ATR pathway itself provided the strongest synthetic lethal interaction. In addition, we found that loss of the structure specific-endonuclease ERCC1-XPF (ERCC4) is synthetic lethal with ATR pathway inhibitors. ERCC1-deficient cells exhibited elevated levels of DNA damage, which was increased further by ATR inhibition. When treated with ATR or CHEK1 inhibitors, ERCC1-deficient cells arrested in S phase and failed to complete cell cycle transit even after drug removal. Notably, triple-negative breast cancer cells and non-small cell lung cancer cells depleted of ERCC1 exhibited increased sensitivity to ATR-pathway targeted drugs. Overall, we concluded that ATR pathway-targeted drugs may offer particular utility in cancers with reduced ATR pathway function or reduced levels of ERCC4 activity. PMID:24662920

  14. RETREATMENT WITH FLUDARABINE AND CYCLOSPORINE FOR ONE CASE OF REFRACTORY PURE RED CELL APLASIA

    Institute of Scientific and Technical Information of China (English)

    Guang-sheng He; Xiang Zhang; De-pei Wu; Ai-ning Sun; Miao Miao; Xiu-li Wang; Zheng-ming Jin

    2008-01-01

    @@ MANY cases of pure red cell aplasia (PRCA) were mediated by over-function of immune cells, and responded well to immunosuppres-sive therapy.1 Sometimes refractory cases also arose. Fludara-bine is an analogue of adenosine resistant to deamination which is widely used for B-chronic lymphocytic leukemia (CLL) and other hematological malignancies.

  15. Passive transport pathways for Ca2+ and Co2+ in human red blood cells

    DEFF Research Database (Denmark)

    Simonsen, Lars Ole; Harbak, Henrik; Bennekou, Poul

    2011-01-01

    The passive transport of calcium and cobalt and their interference were studied in human red cells using (45)Ca and (57)Co as tracers. In ATP-depleted cells, with the ATP concentration reduced to about 1µM, the progress curve for (45)Ca uptake at 1mM rapidly levels off with time, consistent...

  16. Is red blood cell rheology preserved during routine blood bank storage?

    NARCIS (Netherlands)

    Henkelman, Sandra; Dijkstra-Tiekstra, Margriet J.; de Wildt-Eggen, Janny; Graaff, Reindert; Rakhorst, Gerhard; van Oeveren, Willem

    2010-01-01

    BACKGROUND: Red blood cell (RBC) units stored for more than 2 weeks at 4 degrees C are currently considered of impaired quality. This opinion has primarily been based on altered RBC rheologic properties (i.e., enhanced aggregability, reduced deformability, and elevated endothelial cell interaction),

  17. Is red blood cell rheology preserved during routine blood bank storage?

    NARCIS (Netherlands)

    Henkelman, Sandra; Dijkstra-Tiekstra, Margriet J.; de Wildt-Eggen, Janny; Graaff, Reindert; Rakhorst, Gerhard; van Oeveren, Willem

    BACKGROUND: Red blood cell (RBC) units stored for more than 2 weeks at 4 degrees C are currently considered of impaired quality. This opinion has primarily been based on altered RBC rheologic properties (i.e., enhanced aggregability, reduced deformability, and elevated endothelial cell interaction),

  18. T cells exacerbate Lyme borreliosis in TLR2-deficient mice

    Directory of Open Access Journals (Sweden)

    Carrie E. Lasky

    2016-11-01

    Full Text Available Infection of humans with the spirochete, Borrelia burgdorferi, causes Lyme borreliosis and can lead to clinical manifestations such as, arthritis, carditis and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize B. burgdorferi surface lipoproteins primarily via Toll-like receptor (TLR2; however, previous work has demonstrated TLR2-/- mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in B. burgdorferi-infected joints and hearts of C3H TLR2-/- mice. In vivo depletion of either CD4 or CD8 T cells reduced Borrelia-induced joint swelling and lowered tissue spirochete burden, while depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.

  19. A deficiency of interstitial cells of Cajal in Chagasic megacolon.

    Science.gov (United States)

    Hagger, R; Finlayson, C; Kahn, F; De Oliveira, R; Chimelli, L; Kumar, D

    2000-04-12

    Disordered gut motor activity is a feature of patients with Chagas' disease: colonic involvement leads to the development of megacolon and symptoms of constipation. Interstitial cells of Cajal are thought to modulate gut motility. The aim of this study was to test the hypothesis that there is an abnormality of the density of distribution of interstitial cells of Cajal in Chagasic megacolon. Interstitial cells of Cajal were identified by immunohistochemistry using an anti-c-kit antibody. Six patients with Chagasic megacolon were compared with normal controls. The density of distribution of interstitial cells of Cajal was assessed in the longitudinal and circular muscle layers, and in the intermuscular plane of the Chagasic and normal colon. Statistical analysis was performed using Fisher's exact test. The interstitial cells of Cajal density in Chagasic megacolon was much reduced in comparison to normal colonic tissue in the longitudinal muscle layer (P=0.0084), intermuscular plane (P<0.0001), and circular muscle layer (P=0.0051). The lack of interstitial cells of Cajal may play a role in the pathophysiology of the disease, leading to the development of megacolon and symptoms of constipation.

  20. Deformation of Two-Dimensional Nonuniform-Membrane Red Blood Cells Simulated by a Lattice Boltzmann Model

    Institute of Scientific and Technical Information of China (English)

    LI Hua-Bing; JIN Li; QIU Bing

    2008-01-01

    To study two-dimensional red blood cells deforming in a shear flow with the membrane nonuniform on the rigidity and mass, the membrane is discretized into equilength segments. The fluid inside and outside the red blood cell is simulated by the D2Q9 lattice Boltzmann model and the hydrodynamic forces exerted on the membrane from the inner and outer of the red blood cell are calculated by a stress-integration method. Through the global deviation from the curvature of uniform-membrane, we find that when the membrane is nonuniform on the rigidity, the deviation first decreases with the time increases and implies that the terminal profile of the red blood cell is static. To a red blood cell with the mass nonuniform on the membrane, the deviation becomes more large, and the mass distribution affects the profile of the two sides of the flattened red blood cell in a shear flow.

  1. Microvascular blood flow resistance: Role of red blood cell migration and dispersion.

    Science.gov (United States)

    Katanov, Dinar; Gompper, Gerhard; Fedosov, Dmitry A

    2015-05-01

    Microvascular blood flow resistance has a strong impact on cardiovascular function and tissue perfusion. The flow resistance in microcirculation is governed by flow behavior of blood through a complex network of vessels, where the distribution of red blood cells across vessel cross-sections may be significantly distorted at vessel bifurcations and junctions. In this paper, the development of blood flow and its resistance starting from a dispersed configuration of red blood cells is investigated in simulations for different hematocrit levels, flow rates, vessel diameters, and aggregation interactions between red blood cells. Initially dispersed red blood cells migrate toward the vessel center leading to the formation of a cell-free layer near the wall and to a decrease of the flow resistance. The development of cell-free layer appears to be nearly universal when scaled with a characteristic shear rate of the flow. The universality allows an estimation of the length of a vessel required for full flow development, lc ≲ 25D, for vessel diameters in the range 10 μm red blood cell dispersion at vessel bifurcations and junctions on the flow resistance may be significant in vessels which are shorter or comparable to the length lc. Aggregation interactions between red blood cells generally lead to a reduction of blood flow resistance. The simulations are performed using the same viscosity for both external and internal fluids and the RBC membrane viscosity is not considered; however, we discuss how the viscosity contrast may affect the results. Finally, we develop a simple theoretical model which is able to describe the converged cell-free-layer thickness at steady-state flow with respect to flow rate. The model is based on the balance between a lift force on red blood cells due to cell-wall hydrodynamic interactions and shear-induced effective pressure due to cell-cell interactions in flow. We expect that these results can also be used to better understand the flow

  2. Alterations in cell surface area and deformability of individual human red blood cells in stored blood

    CERN Document Server

    Park, HyunJoo; Lee, SangYun; Kim, Kyoohyun; Sohn, Yong-Hak; Jang, Seongsoo; Park, YongKeun

    2015-01-01

    The functionality and viability of stored human red blood cells (RBCs) is an important clinical issue in transfusion. To systematically investigate changes in stored whole blood, the hematological properties of individual RBCs were quantified in blood samples stored for various periods with and without a preservation solution called CPDA-1. With 3-D quantitative phase imaging techniques, the optical measurements of the 3-D refractive index (RI) distributions and membrane fluctuations were done at the individual cell level. From the optical measurements, the morphological (volume, surface area and sphericity), biochemical (hemoglobin content and concentration), and mechanical parameters (dynamic membrane fluctuation) were simultaneously quantified to investigate the functionalities and their progressive alterations in stored RBCs. Our results show that the stored RBCs without CPDA-1 had a dramatic morphological transformation from discocytes to spherocytes within 2 weeks which was accompanied with significant ...

  3. Role of Calcium in Phosphatidylserine Externalisation in Red Blood Cells from Sickle Cell Patients

    Directory of Open Access Journals (Sweden)

    Erwin Weiss

    2011-01-01

    Full Text Available Phosphatidylserine exposure occurs in red blood cells (RBCs from sickle cell disease (SCD patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates Ca2+ entry, providing an obvious link with phosphatidylserine exposure. The role of Ca2+ was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [Ca2+] was increased. This effect was inhibited by dipyridamole, intracellular Ca2+ chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high K+ saline. Ca2+ levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with Ca2+ entry through the deoxygenation-induced pathway (Psickle, activating the Gardos channel. [Ca2+] required for phosphatidylserine scrambling are in the range achievable in vivo.

  4. Effect of iron deficiency on c-kit⁺ cardiac stem cells in vitro.

    Directory of Open Access Journals (Sweden)

    Dongqiang Song

    Full Text Available AIM: Iron deficiency is a common comorbidity in chronic heart failure (CHF which may exacerbate CHF. The c-kit⁺ cardiac stem cells (CSCs play a vital role in cardiac function repair. However, much is unknown regarding the role of iron deficiency in regulating c-kit⁺ CSCs function. In this study, we investigated whether iron deficiency regulates c-kit⁺ CSCs proliferation, migration, apoptosis, and differentiation in vitro. METHOD: All c-kit⁺ CSCs were isolated from adult C57BL/6 mice. The c-kit⁺ CSCs were cultured with deferoxamine (DFO, an iron chelator, mimosine (MIM, another iron chelator, or a complex of DFO and iron (Fe(III, respectively. Cell migration was assayed using a 48-well chamber system. Proliferation, cell cycle, and apoptosis of c-kit⁺ CSCs were analyzed with BrdU labeling, population doubling time assay, CCK-8 assay, and flow cytometry. Caspase-3 protein level and activity were examined with Western blotting and spectrophotometric detection. The changes in the expression of cardiac-specific proteins (GATA-4,TNI, and β-MHC and cell cycle-related proteins (cyclin D1, RB, and pRB were detected with Western blotting. RESULT: DFO and MIM suppressed c-kit⁺ CSCs proliferation and differentiation. They also modulated cell cycle and cardiac-specific protein expression. Iron chelators down-regulated the expression and phosphorylation of cell cycle-related proteins. Iron reversed those suppressive effects of DFO. DFO and MIM didn't affect c-kit⁺ CSCs migration and apoptosis. CONCLUSION: Iron deficiency suppressed proliferation and differentiation of c-kit⁺ CSCs. This may partly explain how iron deficiency affects CHF prognosis.

  5. AMIGO2 modulates T cell functions and its deficiency in mice ameliorates experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Li, Zhilin; Khan, Mohd Moin; Kuja-Panula, Juha; Wang, Hongyun; Chen, Yu; Guo, Deyin; Chen, Zhi Jane; Lahesmaa, Riitta; Rauvala, Heikki; Tian, Li

    2017-05-01

    The immune function of AMIGO2 is currently unknown. Here, we revealed novel roles of AMIGO2 in modulating T-cell functions and EAE using Amigo2-knockout (AMG2KO) mice. Amigo2 was abundantly expressed by murine T helper (Th) cells. Its deficiency impaired transplanted T-cell infiltration into the secondary lymphoid organs and dampened Th-cell activation, but promoted splenic Th-cell proliferation and abundancy therein. AMG2KO Th cells had respectively elevated T-bet in Th1- and GATA-3 in Th2-lineage during early Th-cell differentiation, accompanied with increased IFN-γ and IL-10 but decreased IL-17A production. AMG2KO mice exhibited ameliorated EAE, dampened spinal T-cell accumulation, decreased serum IL-17A levels and enhanced splenic IL-10 production. Adoptive transfer of encephalitogenic AMG2KO T cells induced milder EAE and dampened spinal Th-cell accumulation and Tnf expression. Mechanistically, Amigo2-overexpression in 293T cells dampened NF-kB transcriptional activity, while Amigo2-deficiency enhanced Akt but suppressed GSK-3β phosphorylation and promoted nuclear translocations of NF-kB and NFAT1 in Th-cells. Collectively, our data demonstrate that AMIGO2 is important in regulating T-cell functions and EAE, and may be harnessed as a potential therapeutic target for multiple sclerosis.

  6. Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

    DEFF Research Database (Denmark)

    Patterson, Emily J.; Wilk, Melissa; Langlo, Christopher S.

    2016-01-01

    PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations...... to clarify the link between color vision deficiency and cone dysfunction.  METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone...... tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus....

  7. Differential programming of p53-deficient embryonic cells during rotenone block

    Science.gov (United States)

    Mitochondrial dysfunction has been implicated in chemical toxicities. The present study used an in vitro model to investigate the differential expression of metabolic pathways during cellular stress in p53- efficient embryonic fibroblasts compared to p53-deficient cells. These c...

  8. Maternal vitamin B12 deficiency and abnormal cell-free DNA results in pregnancy

    NARCIS (Netherlands)

    Schuring-Blom, Heleen; Lichtenbelt, Klaske; van Galen, Karin; Elferink, Martin; Weiss, Marjan; Vermeesch, Joris Robert; Page-Christiaens, Lieve

    2016-01-01

    What's Already Known about this Topic? Prenatal testing with cell-free DNA may incidentally identify maternal genetic anomalies and malignancies. What does this Study Add? Profound vitamin B12 deficiency with intramedullary hemolysis may cause abnormal genomic patterns that can be detected by

  9. Induction of protective CTL immunity against peptide transporter TAP-deficient tumors through dendritic cell vaccination.

    Science.gov (United States)

    Chambers, Benedict; Grufman, Per; Fredriksson, Vanoohi; Andersson, Kenth; Roseboom, Marjet; Laban, Sandra; Camps, Marcel; Wolpert, Elisabeth Z; Wiertz, Emmanuel J H J; Offringa, Rienk; Ljunggren, Hans-Gustaf; van Hall, Thorbald

    2007-09-15

    A large proportion of human cancers show deficiencies in the MHC class I antigen-processing machinery. Such defects render tumors resistant to immune eradication by tumoricidal CTLs. We recently identified a unique population of CTL that selectively targets tumor immune-escape variants through recognition of MHC-presented peptides, termed TEIPP (T cell epitopes associated with impaired peptide processing), expressed on cells lacking functional TAP-peptide transporters. Previously, we showed that vaccination with TEIPP peptides mediates protection against TAP-deficient tumors. Here, we further explored the concept of TEIPP-targeted therapy using a dendritic cell (DC)-based cellular vaccine. Impairment of TAP function in DC induced the presentation of endogenous TEIPP antigens by MHC class I molecules, and immunization with these DCs protected mice against the outgrowth of TAP-deficient lymphomas and fibrosarcomas. Immune analysis of vaccinated mice revealed strong TEIPP-specific CTL responses, and a crucial role for CD8(+) cells in tumor resistance. Finally, we show that TEIPP antigens could be successfully induced in wild-type DC by introducing the viral TAP inhibitor UL49.5. Our results imply that immune intervention strategies with TAP-inhibited DC could be developed for the treatment of antigen processing-deficient cancers in humans.

  10. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

    NARCIS (Netherlands)

    Hassan, Amel; Booth, Claire; Brightwell, Alex; Allwood, Zoe; Veys, Paul; Rao, Kanchan; Hoenig, Manfred; Friedrich, Wilhelm; Gennery, Andrew; Slatter, Mary; Bredius, Robbert; Finocchi, Andrea; Cancrini, Caterina; Aiuti, Alessandro; Porta, Fulvio; Lanfranchi, Arnalda; Ridella, Michela; Steward, Colin; Filipovich, Alexandra; Marsh, Rebecca; Bordon, Victoria; Al-Muhsen, Saleh; Al-Mousa, Hamoud; Alsum, Zobaida; Al-Dhekri, Hasan; Al Ghonaium, Abdulaziz; Speckmann, Carsten; Fischer, Alain; Mahlaoui, Nizar; Nichols, Kim E.; Grunebaum, Eyal; Al Zahrani, Daifulah; Roifman, Chaim M.; Boelens, Jaap; Davies, E. Graham; Cavazzana-Calvo, Marina; Notarangelo, Luigi; Gaspar, H. Bobby

    2012-01-01

    Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed o

  11. Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects

    Directory of Open Access Journals (Sweden)

    Naoto Kuroda

    2016-05-01

    Full Text Available Succinate dehydrogenase (SDH-deficient renal cell carcinoma (RCC was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD. The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB , SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

  12. Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

    Science.gov (United States)

    2016-08-15

    SCID; Omenn's Syndrome; Reticular Dysgenesis; Wiskott-Aldrich Syndrome; Bare Lymphocyte Syndrome; Common Variable Immunodeficiency; Chronic Granulomatous Disease; CD40 Ligand Deficiency; Hyper IgM Syndrome; X-linked Lymphoproliferative Disease; Hemophagocytic Lymphohistiocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Langerhan's Cell Histiocytosis

  13. Preparation of Blood-Deficient Model and Research of Angelica Polysaccharide on Enriching Blood in Chickens

    OpenAIRE

    Haifeng Hou; Yongzhan Bao; Qian Li; Wanyu Shi

    2012-01-01

    In this study cyclophosphamide was used to prepare the blood-deficient model. The red blood cell count and hemoglobin content were measured. The experimental chickens presented the symptoms of blood-deficient syndrome, dullness, shrinkinginto oneself, broken winded, loose feather, waxy eyelid, and pale tongue. At the same time, red blood cell count and hemoglobin content decreased significantly. Angelica polysaccharide as the effective component of Angelica Sinensis could significantly increa...

  14. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    Energy Technology Data Exchange (ETDEWEB)

    Oommen, Deepu [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom); Yiannakis, Dennis [Plymouth Oncology Centre, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth PL6 8DH (United Kingdom); Jha, Awadhesh N., E-mail: a.jha@plymouth.ac.uk [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom)

    2016-02-15

    Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

  15. Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion. Nonlinear decay of adult red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Gemert, Martin J C van; Wijngaard, Jeroen P H M van den [Laser Centre and Department of Obstetrics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Pasman, Suzanne A; Vandenbussche, Frank P H A [Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Centre, Leiden (Netherlands); Lopriore, Enrico [Division of Neonatology, Department of Pediatrics, Leiden University Medical Centre, Leiden (Netherlands)], E-mail: m.j.vangemert@amc.uva.nl

    2008-07-07

    Recently, we derived equations relating the flow of adult red blood cells through a placental arterio-venous anastomosis with intra-uterine and post-natal measured adult hemoglobin concentrations. In this letter, we re-derived the equations, now including a more realistic nonlinear decay of adult red blood cells, and re-evaluated the measurement accuracy of the arterio-venous flow and the lifetime of the red blood cells. (letter to the editor)

  16. Iron deficiency anaemia.

    Science.gov (United States)

    Lopez, Anthony; Cacoub, Patrice; Macdougall, Iain C; Peyrin-Biroulet, Laurent

    2016-02-27

    Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin recept