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Sample records for deficient red cells

  1. Neonatal nucleated red blood cells in G6PD deficiency.

    Science.gov (United States)

    Yeruchimovich, Mark; Shapira, Boris; Mimouni, Francis B; Dollberg, Shaul

    2002-05-01

    The objective of this study is to study the absolute number of nucleated red blood cells (RBC) at birth, an index of active fetal erythropoiesis, in infants with G6PD deficiency and in controls. We tested the hypothesis that hematocrit and hemoglobin would be lower, and absolute nucleated RBC counts higher, in the G6PD deficient and that these changes would be more prominent in infants exposed passively to fava bean through maternal diet. Thirty-two term infants with G6PD deficiency were compared with 30 term controls. Complete blood counts with manual differential counts were obtained within 12 hours of life. Absolute nucleated RBC and corrected leukocyte counts were computed from the Coulter results and the differential count. G6PD deficient patients did not differ from controls in terms of gestational age, birth weight, or Apgar scores or in any of the hematologic parameters studied, whether or not the mother reported fava beans consumption in the days prior to delivery. Although intrauterine hemolysis is possible in G6PD deficient fetuses exposed passively to fava beans, our study supports that such events must be very rare.

  2. Red cell distribution width in the diagnosis of iron deficiency anemia and thalassemia trait

    International Nuclear Information System (INIS)

    Adil, M.M.; Junaid, A.; Zaman, I.; Ishtiaque, Z.B.

    2010-01-01

    To evaluate diagnostic importance of Red Cell Distribution Width (RDW) in differentiating iron deficiency anemia from Thalassemia trait. A total of 100 cases aged 5 months to 50 years of either sex with diagnosed iron deficiency anemia or thalassemia trait were compared with respect to their RDW value. RDW value in iron deficiency anemia was between 36.2% to 55.2% (Mean 44.1%). The range of RDW in Thalassemia trait was 14.7% to 24.9% (Mean 19.8%). Conclusions The very high range of RDW in iron deficiency anemia as compared to slight elevation of the value in thalassemia trait in our study suggests that RDW value obtained from simple Complete Blood Counts (CBC) can help in differentiating the two pathologies. (author)

  3. The Relationship of Vitamin B12 Deficiency and Red Cell Distribution Width-Platelet Ratio

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    Nigar Yilmaz

    2016-09-01

    Full Text Available Objective: We aimed to investigate the relationship between vitamin B12 deficiency and red cell distribution widthplatelet ratio (RPR, and the variations in the parameters on vitamin B12 treatment. Methods: One hundred fifty-four patients with untreated vitamin B12 deficiency (56% men, mean age: 50 ± 12.7 years (untreated group, 86 patients with vitamin B12 deficiency (62% men, mean age: 42 ± 20.7 years on vitamin B12 treatment (treated group, and 92 age- and sex-matched control group (54% men, mean age: 45 ± 15.1 years were included in the study. Hematological parameters were evaluated by the method of laser-based flow cytometric impedance, using an automated blood cell counter (ABX Pentra 120 Hematology Blood Analyzer. Results: RPR was significantly reduced in treated group compared with untreated group (4.88 ± 1.06; 6.13 ± 1.27; p0.05. Conclusion: We proposed that vitamin B12 deficiency has effects on RPR and supplementation with vitamin B12 corrects the RPR levels. J Clin Exp Invest 2016; 7 (3: 211-215

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

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    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

  5. Diagnosis of iron deficiency anemia using density-based fractionation of red blood cells.

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    Hennek, Jonathan W; Kumar, Ashok A; Wiltschko, Alex B; Patton, Matthew R; Lee, Si Yi Ryan; Brugnara, Carlo; Adams, Ryan P; Whitesides, George M

    2016-10-05

    Iron deficiency anemia (IDA) is a nutritional disorder that impacts over one billion people worldwide; it may cause permanent cognitive impairment in children, fatigue in adults, and suboptimal outcomes in pregnancy. IDA can be diagnosed by detection of red blood cells (RBCs) that are characteristically small (microcytic) and deficient in hemoglobin (hypochromic), typically by examining the results of a complete blood count performed by a hematology analyzer. These instruments are expensive, not portable, and require trained personnel; they are, therefore, unavailable in many low-resource settings. This paper describes a low-cost and rapid method to diagnose IDA using aqueous multiphase systems (AMPS)-thermodynamically stable mixtures of biocompatible polymers and salt that spontaneously form discrete layers having sharp steps in density. AMPS are preloaded into a microhematocrit tube and used with a drop of blood from a fingerstick. After only two minutes in a low-cost centrifuge, the tests (n = 152) were read by eye with a sensitivity of 84% (72-93%) and a specificity of 78% (68-86%), corresponding to an area under the curve (AUC) of 0.89. The AMPS test outperforms diagnosis by hemoglobin alone (AUC = 0.73) and is comparable to methods used in clinics like reticulocyte hemoglobin concentration (AUC = 0.91). Standard machine learning tools were used to analyze images of the resulting tests captured by a standard desktop scanner to 1) slightly improve diagnosis of IDA-sensitivity of 90% (83-96%) and a specificity of 77% (64-87%), and 2) predict several important red blood cell parameters, such as mean corpuscular hemoglobin concentration. These results suggest that the use of AMPS combined with machine learning provides an approach to developing point-of-care hematology.

  6. 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.

  7. [Current status of vitamin A deficiency in preschool children in Dongguan, China and the effect of vitamin A on serum ferritin and red blood cell parameters].

    Science.gov (United States)

    Zhang, Zhen-Hong; Ni, Ming; Hu, Yuan

    2018-03-01

    To investigate the current status of vitamin A deficiency in preschool children in Dongguan, China, as well as the effect of vitamin A on serum ferritin, red blood cell, and reticulocyte parameters. Cluster sampling was performed from April 2015 to December 2016 to select 2 085 preschool children (3-6 years old) without any disease in Dongguan. Routine blood test, reticulocyte count, serum ferritin measurement, hemoglobin electrophoresis, and vitamin A measurement were performed for all children. The associations of age and sex with vitamin A and serum ferritin concentrations were analyzed. The effect of vitamin A concentration on serum ferritin, red blood cell, and reticulocyte parameters and the effect of reduced iron storage caused by vitamin A deficiency on red blood cell parameters were evaluated. Of the 2 085 children, 140 (6.71%) had reduced iron storage, and 678 (32.52%) had vitamin A deficiency. Among the 678 children with vitamin A deficiency, 647 (95.4%) had subclinical deficiency and 31 (4.6%) had clinical deficiency. There was no significant difference in vitamin A concentration between boys and girls, however girls had a significantly higher serum ferritin concentration than boys (P<0.05). The clinical vitamin A deficiency group had a significantly higher serum ferritin concentration than the subclinical vitamin A deficiency group and the normal group (P<0.05). In cases of vitamin A deficiency, the reduced iron storage group had significant reductions in mean corpuscular volume and mean corpuscular hemoglobin than the normal iron storage group (P<0.05). Compared with the normal vitamin A group, the vitamin A deficiency group had significantly lower hemoglobin concentration, mean corpuscular hemoglobin, red blood cell count, hematocrit, absolute reticulocyte count, reticulocyte percentage, and reticulocyte hemoglobin content, as well as a significantly higher mean corpuscular volume (P<0.05). Vitamin A deficiency is prevalent in preschool children

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

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    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]. Keywords: G6PD deficiency, Red blood cell storage lesion, Oxidative stress, Cell fragility, Microparticles

  9. Influence of iron deficiency in the radiopharmaceutical behavior of red blood cells labeled with 99mTc(99mTC-RBC)

    International Nuclear Information System (INIS)

    Calmanovici, G.; Salgueiro, M.J.; Pernas, L.; Collia, N.; Leonardi, N.; Zubillaga, M.

    2005-01-01

    Full text: Red blood cells (RBCs) labeled with 99m Tc are commonly used in the evaluation of cardiac function, gastrointestinal tract bleeding, red blood cell volume or splenic sequestration. Generally stannous ion is used as reducing agent. A proposed mechanism is that once the stannous ion (Sn) and the pertechnetate ( 99m Tc) reach the interior of the RBC, the radionuclide is mainly house in the β-chain of hemoglobin. The aim of this study was to determine if hemoglobin content reduction, an indicator of iron deficiency anemia, could affect the efficiency of RBC labeling and the biological distribution of this radiopharmaceutical. We studied 30 rats fed for 3 weeks after weaning with diets with iron contents of 6.5 ppm (group A), 18 ppm (group B) and 100 ppm (control). For all groups, the labeling yields were always higher than 97%; the percentage of radioactivity was mostly founded in blood with almost negligible radioactivity the rest of the studied organs. We can conclude that the decrease in hemoglobin content, an indicator of iron deficiency anemia, does not interfere neither in the labeling nor in the biodistribution of red blood cells labeled with 99m Tc. (author)

  10. Avoiding Anemia: Boost Your Red Blood Cells

    Science.gov (United States)

    ... Issues Subscribe January 2014 Print this issue Avoiding Anemia Boost Your Red Blood Cells En español Send ... Disease When Blood Cells Bend Wise Choices Preventing Anemia To prevent or treat iron-deficiency anemia: Eat ...

  11. Red blood cell production

    Science.gov (United States)

    ... bone marrow of bones. Stem cells in the red bone marrow called hemocytoblasts give rise to all of the formed elements in blood. If a hemocytoblast commits to becoming a cell called a proerythroblast, it will develop into a new red blood cell. The formation of a red blood ...

  12. 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.

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

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    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.

  14. Observation on the changes of serum erythropoietin (EPO) and ferritin (SF) levels after preserved red cells (PRC) transfusion in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Li Keqin; Lv Haijun; Li Xinghua

    2008-01-01

    Objective: To study the changes of serum EPO and SF levels after preserved red cells transfusion in patients with IDA. Methods: Serum EPO and SF levels were detected with RIA both before and after transfusing preserved red cells in 35 patients with IDA as well as in 30 controls. Results: Before transfusion serum EPO levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Transfusing preserved red cells is an effective treatment and has important role in clinical application. (authors)

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  16. Noninferiority of glucose-6-phosphate dehydrogenase deficiency diagnosis by a point-of-care rapid test vs the laboratory fluorescent spot test demonstrated by copper inhibition in normal human red blood cells.

    Science.gov (United States)

    Baird, J Kevin; Dewi, Mewahyu; Subekti, Decy; Elyazar, Iqbal; Satyagraha, Ari W

    2015-06-01

    Tens of millions of patients diagnosed with vivax malaria cannot safely receive primaquine therapy against repeated attacks caused by activation of dormant liver stages called hypnozoites. Most of these patients lack access to screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency, a highly prevalent disorder causing serious acute hemolytic anemia with primaquine therapy. We optimized CuCl inhibition of G6PD in normal red blood cells (RBCs) to assess G6PD diagnostic technologies suited to point of care in the impoverished rural tropics. The most widely applied technology for G6PD screening-the fluorescent spot test (FST)-is impractical in that setting. We evaluated a new point-of-care G6PD screening kit (CareStart G6PD, CSG) against FST using graded CuCl treatments to simulate variable hemizygous states, and varying proportions of CuCl-treated RBC suspensions to simulate variable heterozygous states of G6PD deficiency. In experiments double-blinded to CuCl treatment, technicians reading FST and CSG test (n = 269) classified results as positive or negative for deficiency. At G6PD activity ≤40% of normal (n = 112), CSG test was not inferior to FST in detecting G6PD deficiency (P = 0.003), with 96% vs 90% (P = 0.19) sensitivity and 75% and 87% (P = 0.01) specificity, respectively. The CSG test costs less, requires no specialized equipment, laboratory skills, or cold chain for successful application, and performs as well as the FST standard of care for G6PD screening. Such a device may vastly expand access to primaquine therapy and aid in mitigating the very substantial burden of morbidity and mortality imposed by the hypnozoite reservoir of vivax malaria. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Identifying activated T cells in reconstituted RAG deficient mice using retrovirally transduced Pax5 deficient pro-B cells.

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    Nadesan Gajendran

    Full Text Available Various methods have been used to identify activated T cells such as binding of MHC tetramers and expression of cell surface markers in addition to cytokine-based assays. In contrast to these published methods, we here describe a strategy to identify T cells that respond to any antigen and track the fate of these activated T cells. We constructed a retroviral double-reporter construct with enhanced green fluorescence protein (EGFP and a far-red fluorescent protein from Heteractis crispa (HcRed. LTR-driven EGFP expression was used to enrich and identify transduced cells, while HcRed expression is driven by the CD40Ligand (CD40L promoter, which is inducible and enables the identification and cell fate tracing of T cells that have responded to infection/inflammation. Pax5 deficient pro-B cells that can give rise to different hematopoietic cells like T cells, were retrovirally transduced with this double-reporter cassette and were used to reconstitute the T cell pool in RAG1 deficient mice that lack T and B cells. By using flow cytometry and histology, we identified activated T cells that had developed from Pax5 deficient pro-B cells and responded to infection with the bacterial pathogen Listeria monocytogenes. Microscopic examination of organ sections allowed visual identification of HcRed-expressing cells. To further characterize the immune response to a given stimuli, this strategy can be easily adapted to identify other cells of the hematopoietic system that respond to infection/inflammation. This can be achieved by using an inducible reporter, choosing the appropriate promoter, and reconstituting mice lacking cells of interest by injecting gene-modified Pax5 deficient pro-B cells.

  18. Study on changes of serum ferritin (SF), folic acid (FA) and vitamin B12 levels after transfusion of preserved red cells (PRC) in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Liu Hongsu; Li Xinhua; Li Keqin

    2008-01-01

    Objective: To explore the changes of serum SF, FA and VitB 12 levels after transfusion of preserved red cells in patients with IDA. Methods: Serum SF, FA and VitB 12 levels (with RIA) were detected both before and after transfusion of preserved red cells in 32 patients with IDA as well as in 35 controls. Results: Before transfusion of preserved red cells, the serum SF levels were significantly lower than those in controls (P 12 levels were significantly higher (P 12 were not much different from those in the controls. Conclusion: Transfusion of preserved red cells proves to be very useful. (authors)

  19. A Review of Prevention, Diagnosis and Treatment of Relative Energy Deficiency in Sport (RED-S) in Artistic (Synchronized) Swimming.

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    Robertson, Sherry; Mountjoy, Margo

    2018-05-03

    The syndrome Relative Energy Deficiency in Sport (RED-S) is a clinical entity characterized by low energy availability (LEA), which can negatively affect the health and performance of both male and female athletes. The underlying mechanism of RED-S is an inadequacy of dietary energy to support optimal health and performance. This syndrome refers to impaired physiological function including metabolic rate, menstrual function, bone health, immunity, protein synthesis, and cardiovascular health, with psychological consequences which can either precede (through restrictive dietary habits) or result from RED-S. The term RED-S extends beyond the condition termed the "Female Athlete Triad". Formerly known as synchronized swimming, artistic swimming is an Olympic sport requiring a high level of fitness as well as technical skill and artistry. The risk of RED-S is high in artistic swimming as it is an aesthetic, judged sport with an emphasis on a lean physique. RED-S is of significant concern in the sport of artistic swimming because of the potential negative effects on physical and mental health as well as consequences on athletic performance. This paper reviews health and performance consequences associated with LEA resulting in RED-S in artistic swimming. Medical and nutritional considerations specific to artistic swimming are reviewed and methods to help detect and manage RED-S are discussed. Prevention and management of RED-S in this athlete population should be a priority for coaches and the sport medicine professionals working with artistic swimming athletes should utilize the RED-S CAT, a Clinical Assessment Tool for screening and managing RED-S.

  20. Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells

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    Müller Sylke

    2009-05-01

    Full Text Available Abstract Background Plasmodium falciparum-parasitized red blood cells (RBCs are equipped with protective antioxidant enzymes and heat shock proteins (HSPs. The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Methods Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. Results In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of

  1. Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells.

    Science.gov (United States)

    Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

    2009-05-29

    Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of

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

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    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.

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

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    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.

  4. Human Red Cells With Paroxysmal Nocturnal Haemoglobinuria ...

    African Journals Online (AJOL)

    The purified cells were used as hosts for the culture of P.falciparum in vitro. Results show that GPI-linked molecules on the red cell surface are not required for the efficient entry of the parasites, and that the PNH red cells are competent to sustain the growth of P.falciparum. Nigerian Quarterly Journal of Hospital Medicine Vol ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

  6. Red Blood Cell Storage Lesion

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    Daryl J. Kor

    2009-10-01

    Full Text Available The past two decades have witnessed increased scrutiny regarding efficacy and risk of the once unquestioned therapy of red blood cell (RBC transfusion. Simultaneously, a variety of changes have been identified within the RBC and storage media during RBC preservation that are correlated with reduced tissue oxygenation and transfusion-associated adverse effects. These alterations are collectively termed the storage lesion and include extensive biochemical, biomechanical, and immunologic changes involving cells of diverse origin. Time-dependent falls is 2,3-diphosphoglycerate, intracellular RBC adenosine triphosphate, and nitric oxide have been shown to impact RBC deformability and delivery of oxygen to the end-organ. The accumulation of biologic response modifiers such as soluble CD40 ligand (sCD40L, lysophosphatidylcholine (lyso-PC, and Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES have been associated with altered recipient immune function as well. This review will address the alterations occurring within the RBC and storage media during RBC preservation and will address the potential clinical consequence thereof.

  7. 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

  8. 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...

  9. Uptake of carnitine by red blood cells

    International Nuclear Information System (INIS)

    Campa, M.; Borum, P.

    1986-01-01

    A significant amount of blood carnitine (70% of cord blood and 40% of blood from healthy adults) is partitioned into the red blood cell compartment of whole blood. Data indicate that the plasma compartment and the red blood cell compartment of whole blood represent different metabolic pools of carnitine. There are no data to indicate that red blood cells synthesize carnitine, but our understanding of the uptake of carnitine by red blood cells is negligible. Red blood cells were obtained from healthy adults, washed twice with normal saline, and used for uptake experiments. When the cells were incubated at 37 0 C in the presence of 14 C-carnitine, radioactivity was found both in the soluble cytosolic and membrane fractions of the cells following lysis. The uptake was dependent upon the time of incubation, temperature of incubation, and carnitine concentration in the incubation medium. Washed red blood cell membranes incubated with 14 C-carnitine showed specific binding of radioactivity. These data are consistent with the hypothesis that red blood cells have an uptake mechanism for L-carnitine

  10. Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency.

    Science.gov (United States)

    Ozen, S; Aldemir, O

    2012-01-01

    The patient is a 2.8 years old male who is extremely obese and severe hyperphagic from birth. He had seizures attacks and apnea from the second week of his life. He has red hair and serum cortisol and ACTH levels are very low. We examined our patient as a hypocortisolism due to ACTH deficiency and central hypothyrodism. After the corticosteroid replacement therapy hair color changed to brown. We performed molecular genetic analysis at the Institue for Experimental Pediatric Endocrinology laboratory in Berlin, Germany by Krude H. and found compound heterozygous mutations. As a result the case is diagnosed as POMC deficiency.

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  13. Red-Green Colour Deficiencies and the Study of Science, Computer ...

    African Journals Online (AJOL)

    Colour blindness is the inability to perceive differences between some or all colours that other people can distinguish. It is most often of genetic nature but may also occur because of eye, nerve or brain damage or due to exposure to some chemicals. The most common type of colour vision deficiency is red-green colour ...

  14. Shape memory of human red blood cells.

    Science.gov (United States)

    Fischer, Thomas M

    2004-05-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spheres. Shape excursions were induced by shear flow. In virtually all red cells, a shape memory was found. After stop of flow and during the return of the latex spheres to the original location, the red cell shape was biconcave. The return occurred by a tank-tread motion of the membrane. The memory could not be eliminated by deforming the red cells in shear flow up to 4 h at room temperature as well as at 37 degrees C. It is suggested that 1). the characteristic time of stress relaxation is >80 min and 2). red cells in vivo also have a shape memory.

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

    OpenAIRE

    Caprio, Di; Stokes, Chris; 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....

  16. Moving from efficacy to effectiveness: red palm oil's role in preventing vitamin A deficiency.

    Science.gov (United States)

    Rice, Amy L; Burns, Jennifer B

    2010-06-01

    Vitamin A deficiency is one of the most widespread nutritional deficiencies worldwide. Hundreds of millions of children and tens of millions of women living in Sub-Saharan Africa and Southeast Asia are at particularly high risk of the adverse health consequences associated with this largely preventable condition. Red palm oil comes from oil palms that are traditionally grown in tropical regions of West Africa and are now cultivated on a large-scale commercial basis in Southeast Asia. Red palm oil is the richest naturally occurring source of beta-carotene, a carotenoid that the human body can convert into usable vitamin A (retinol). This paper reviews a series of key intervention studies designed to investigate the impact of using red palm oil-based interventions to improve vitamin A status. These included studies from Africa, Asia, and Latin America in which red palm oil was used (or proposed for use) (1) as a dietary supplement, (2) as an in-home fortificant, (3) to fortify foods used for distribution in targeted supplementary feeding programs, and (4) to fortify staple food products. Overall, the results suggest that red palm oil is highly efficacious in improving vitamin A status among populations at risk of vitamin A deficiency. The time has come to move beyond trials of biological efficacy and focus on conducting operational research projects, effectiveness trials, and cost-benefit analyses that will help expand the use of red palm oil in areas where it is likely to be well accepted but remains underutilized as a dietary source of provitamin A.

  17. How to display data by color schemes compatible with red-green color perception deficiencies.

    Science.gov (United States)

    Geissbuehler, Matthias; Lasser, Theo

    2013-04-22

    Visualization of data concerns most scientists. The use of color is required in order to display multidimensional information. In addition, color encoding a univariate image can improve the interpretation significantly. However up to 10% of the adult male population are affected by a red-green color perception deficiency which hampers the correct interpretation and appreciation of color encoded information. This work attempts to give guidelines on how to display a given dataset in a balanced manner. Three novel color maps are proposed providing readers with normal color perception a maximum of color contrast while being a good compromise for readers with color perception deficiencies.

  18. Evaluation of low red blood cell mean corpuscular volume in an apheresis donor population.

    Science.gov (United States)

    Bryant, Barbara J; Hopkins, Julie A; Arceo, Sarah M; Leitman, Susan F

    2009-09-01

    Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell mean corpuscular volume (MCV) values (or=12.5 g/dL) could be due to iron deficiency or hemoglobinopathy. The etiology of a low MCV in a healthy apheresis donor population was assessed. Predonation samples for CBC were obtained from 1162 consecutive apheresis donors. Donors with a MCV of less than 80 fL were evaluated by CBC, iron studies (ferritin, serum iron, transferrin, percentage of transferrin saturation), and hemoglobin (Hb) electrophoresis. Iron deficiency was defined as a ferritin value below the reference range. Beta chain Hb variants were determined by Hb electrophoresis. Alpha thalassemia trait was presumed if the red blood cell (RBC) count was elevated, no variant Hbs were detected, and the iron studies were within normal ranges. In a 19-month period, 33 of 1162 apheresis donors had low MCV values. Iron deficiency was present in 64%; 49% had isolated iron deficiency and 15% had iron deficiency plus hemoglobinopathy. Hemoglobinopathy without concomitant iron deficiency was found in the remaining 36%. Iron deficiency is present in the majority of apheresis donors with repeatedly low MCV values and Hb levels of 12.5 g/dL or more. Hemoglobinopathy is also commonly present but may not be easily recognized in the setting of iron deficiency. The MCV is a useful screening tool to detect iron deficiency and hemoglobinopathy. Low MCV values should be investigated to determine if iron replacement therapy is indicated.

  19. How to display data by color schemes compatible with red-green color perception deficiencies

    OpenAIRE

    Geissbuehler, Matthias; Lasser, Theo

    2013-01-01

    Visualization of data concerns most scientists. The use of color is required in order to display multidimensional information. In addition, color encoding a univariate image can improve the interpretation significantly. However up to 10% of the adult male population are affected by a red-green color perception deficiency which hampers the correct interpretation and appreciation of color encoded information. This work attempts to give guidelines on how to display a given dataset in a balanced ...

  20. Artificial Red Cells with Polyhemoglobin Membranes.

    Science.gov (United States)

    1981-09-01

    Y. Reciprocal binding of oxygen and diphosphoglycerate by human hemoglobin. Proc. Natl. Acad. Sci. USA 59:526-532, 1968. 12. Bunn, H. F., Seal, U. S...and Scott, A. F. The role of 2,3- diphosphoglycerate in mediating hemoglobin function of mammalian red cells. Ann. N.Y. Acad. Sciences 241:498-519

  1. Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation.

    Science.gov (United States)

    Barut Selver, Özlem; Yağcı, Ayşe; Eğrilmez, Sait; Gürdal, Mehmet; Palamar, Melis; Çavuşoğlu, Türker; Ateş, Utku; Veral, Ali; Güven, Çağrı; Wolosin, Jose Mario

    2017-10-01

    The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using

  2. Shape Memory of Human Red Blood Cells

    OpenAIRE

    Fischer, Thomas M.

    2004-01-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spher...

  3. 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...

  4. 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

  5. Mechanisms of immune red cell destruction, and red cell compatibility testing

    International Nuclear Information System (INIS)

    Garratty, G.

    1983-01-01

    The immune destruction of red cells can occur as a complement-mediated intravascular process, or extravascularly, where the red cells are destroyed by macrophages following interaction with cell-bound IgG1, IgG3, and/or C3b. Many of the factors that affect this in vivo destruction are not taken into account during in vitro pretransfusion compatibility testing. At present, even by use of more elaborate tests, it is difficult to accurately predict the fate of a transfused unit of blood. By using some simple information, such as antibody specificity and thermal range, it is sometimes possible to predict the outcome of transfusing a unit of blood that is incompatible in vitro. At other times it may be necessary to utilize 51 Cr-labeled red cells to determine the risk of transfusing such units. Because of the paucity of reported clinical correlations, macrophage/monocyte monolayer assays are of little practical value at present

  6. NMR water-proton spin-lattice relaxation time of human red blood cells and red blood cell suspensions

    International Nuclear Information System (INIS)

    Sullivan, S.G.; Rosenthal, J.S.; Winston, A.; Stern, A.

    1988-01-01

    NMR water-proton spin-lattice relaxation times were studied as probes of water structure in human red blood cells and red blood cell suspensions. Normal saline had a relaxation time of about 3000 ms while packed red blood cells had a relaxation time of about 500 ms. The relaxation time of a red blood cell suspension at 50% hematocrit was about 750 ms showing that surface charges and polar groups of the red cell membrane effectively structure extracellular water. Incubation of red cells in hypotonic saline increases relaxation time whereas hypertonic saline decreases relaxation time. Relaxation times varied independently of mean corpuscular volume and mean corpuscular hemoglobin concentration in a sample population. Studies with lysates and resealed membrane ghosts show that hemoglobin is very effective in lowering water-proton relaxation time whereas resealed membrane ghosts in the absence of hemoglobin are less effective than intact red cells. 9 refs.; 3 figs.; 1 table

  7. Thrombocytopenia responding to red blood cell transfusion

    International Nuclear Information System (INIS)

    Mubarak, Ahmad A.; Awidi, Abdalla; Rasul, Kakil I.; Al-Homsi, Ussama

    2004-01-01

    Three patients with severe symptomatic iron defficiency anemia and thrombocytopenia had a significant rise in the platelet count a few days following packed red blood cell transfusion. Pretransfusion platelet count of of patient one was 17x10/L. 22x10/Lin patient two and 29x10/L in patient three. On the 6th day of post tranfusion, the platelet count rose to 166x10/Lin patient one, 830x10/L in patient two and 136x10/L in patient three. The possible mechcnism behind such an unreported observation are discussed. (author)

  8. Perfluoroalkyl substances and beta cell deficient diabetes.

    Science.gov (United States)

    Conway, Baqiyyah; Innes, Karen E; Long, Dustin

    2016-08-01

    Perfluoroalkyl substances (PFAS) are synthetic hydrocarbons shown to preserve pancreatic islet cell viability and reduce islet cell hypoxia and apoptosis. We investigated the relationship of serum PFAS with diabetes, and whether this varied by diabetes type. 6,460 individuals with and 60,439 without diabetes from the C8 Health Project, were categorized into three groups: type 1 (n=820), type 2 (n=4,291), or uncategorized diabetes (n=1,349, missing data on diabetes type or diabetes based on blood sugar at study entry). Four PFAS were investigated: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononaoic acid (PFNA). PFAS levels were significantly lower in those with diabetes, and lowest in those with type 1 diabetes. In age and sex adjusted analyses, ORs (CI) for type 1, type 2, and uncategorized diabetes compared to no diabetes were 0.59 (0.54-0.64), 0.74 (0.71-0.77), 0.84 (0.78-0.90), respectively for PFHxS; 0.69 (0.65-0.74), 0.87 (0.89-0.91), 0.92 (0.88-0.97), respectively for PFOA; 0.65 (0.61-0.70), 0.86 (0.82-0.90), 0.93 (0.86-1.03), respectively for PFOS; and 0.65 (0.57-0.74), 0.94 (0.88-1.00), 0.95 (0.85-1.06), respectively for PFNA. Further adjustment for eGFR and other covariates did not eliminate these inverse associations. PFAS levels were negatively associated with diabetes. This inverse relationship was strongest for type 1 diabetes, suggesting the relationship with serum PFAS may vary with the severity of islet cell deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    /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......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...... 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...

  10. Red cell concentrate storage and transport temperature.

    Science.gov (United States)

    Hancock, V; Cardigan, R; Thomas, S

    2011-10-01

    This study investigated the current U.K. guidelines for storage and transport of red cell concentrates (RCC) in saline, adenine, glucose and mannitol (SAGM). The guidelines stipulate storage at 2-6 °C but allow exposure to between 1-10 °C core temperature in a single occurrence of less than 5 h and a surface temperature of 2-10 °C for no more than 12 h during transportation. Twenty RCC units in SAGM were selected on the day of blood collection (day 0) and in vitro quality was tested pre- and post-temperature deviation at 10 °C and up to day 42 of storage. Each group of 10 RCC units was incubated for either 12 h or for both 5 and 12 h. Haemolysis was below the 0·8% U.K. limit at day 42 in all units, although there was an unexpected trend towards lower haemolysis in packs incubated for 5 and 12 h rather than just 12 h alone. Supernatant potassium was significantly higher than reference data on day 35 (P levels of adenosine triphosphate and, 2,3-diphosphoglycerate to reference data from previous studies, throughout storage. These results suggest that exposure to 10 °C for 12 h or for 5 and 12 h did not adversely affect in vitro red cell quality for the remainder of the components shelf life. © 2011 The Authors. Transfusion Medicine © 2011 British Blood Transfusion Society.

  11. Red blood cell alloimmunization in sickle cell disease patients in ...

    African Journals Online (AJOL)

    Objective: Alloimmunization is a recognized complication of red blood cell (RBC) transfusion and causes delayed hemolytic transfusion reactions and provides problems sourcing compatible blood for future transfusions. The objective of this study was to determine the frequency of RBC alloimmunization in SCD patients in ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... complications, including heart failure and development delays in children. Explore this Health ... red blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... these usually go away within a day or two. Red blood cell transfusions. These may be used ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... red blood cells, called hemolysis . Hemolysis, in this case, is caused by strong muscle contractions and the ... to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your blood may be normal even if the total amount of iron in your body is low. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... lead in their blood from their environment or water. Lead interferes with the body’s ability to make ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... in our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ... and where to find more information. Causes Your body needs iron to make healthy red blood cells. ...

  20. Red Blood Cell Count Automation Using Microscopic Hyperspectral Imaging Technology.

    Science.gov (United States)

    Li, Qingli; Zhou, Mei; Liu, Hongying; Wang, Yiting; Guo, Fangmin

    2015-12-01

    Red blood cell counts have been proven to be one of the most frequently performed blood tests and are valuable for early diagnosis of some diseases. This paper describes an automated red blood cell counting method based on microscopic hyperspectral imaging technology. Unlike the light microscopy-based red blood count methods, a combined spatial and spectral algorithm is proposed to identify red blood cells by integrating active contour models and automated two-dimensional k-means with spectral angle mapper algorithm. Experimental results show that the proposed algorithm has better performance than spatial based algorithm because the new algorithm can jointly use the spatial and spectral information of blood cells.

  1. Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

    Science.gov (United States)

    Chico, Verónica; Puente-Marin, Sara; Nombela, Iván; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Villena, Alberto; Mercado, Luis; Coll, Julio; Ortega-Villaizan, María Del Mar

    2018-04-19

    Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright⁻Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells.

  2. Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

    Science.gov (United States)

    Chico, Verónica; Puente-Marin, Sara; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Mercado, Luis; Coll, Julio

    2018-01-01

    Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright–Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells. PMID:29671811

  3. 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.

  4. Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion.

    Science.gov (United States)

    Ameen, Reem; Al Shemmari, Salem; Al-Bashir, Abdulaziz

    2009-08-01

    Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients. A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity. Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations. This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD 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. 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...... 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....

  7. 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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8540 Red cell lysing reagent...

  8. 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 864.7100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7100 Red blood cell...

  9. Restoring balance to B cells in ADA deficiency.

    Science.gov (United States)

    Luning Prak, Eline T

    2012-06-01

    It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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 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)

  11. 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)

  12. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... Videos for Educators Search English Español Iron-Deficiency Anemia KidsHealth / For Parents / Iron-Deficiency Anemia What's in ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  13. Potential use of Red Palm Oil in Combating Vitamin A deficiency in India

    Directory of Open Access Journals (Sweden)

    K Manorama

    2014-12-01

    Full Text Available Deficiency of vitamin A has long been recognized as a serious and preventable nutritional disease.  Various intervention strategies have been implemented to combat the problem.  Massive dosing of the vitamin has the advantage of immediate implementation but suffers from the disadvantage in that it applies to the isolated nutrient and requires repetitive administration. Natural food sources regularly included in diets offer a more viable long term solution. Red palm oil (RPO can emerge as a viable alternative to other vitamin A rich foods, since it contains enormous amounts of natural carotenoids to the tune of around 700 PPM, the predominant ones being a and b carotene which have the highest biological potential for vitamin A conversion.  Value addition of palm oil for edible purposes results in several nutritionally rich products like edible grade red palm oil (RPO, deacidified, deodourised RPOlein, isolated carotenoids and refined, bleached and deodourized palmolein oil RBD palmolein. RBD palmolein oil can serve as a replacement for any other commonly used edible oil, but has little additional advantage over other edible oils, stripped of its carotenoids. However, it’s naturally rich composition of tocopherols and tocotrienols, as well as the balanced fatty acid composition, makes it more superior to other edible oils used for dietary purposes. Addition of RBD palmolein to hydrogenated vegetable oil confers no advantage, and paradoxically, decreases it’s beneficial properties making it a more harmful vegetable oil from the cardiovascular health angle, because of conversion of fatty acids from the cis to trans type.

  14. Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates.

    Science.gov (United States)

    Franken, Lars; Klein, Marika; Spasova, Marina; Elsukova, Anna; Wiedwald, Ulf; Welz, Meike; Knolle, Percy; Farle, Michael; Limmer, Andreas; Kurts, Christian

    2015-08-11

    A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen.

  15. From red cells to soft porous lubrication.

    Science.gov (United States)

    Wu, Qianhong; Zhu, Zenghao; Nathan, Rungun

    2017-11-01

    In this paper, we report a novel experimental study to examine the lubrication theory for highly compressible porous media (Feng & Weinbaum, JFM, 422, 282, 2000), which was applied to the frictionless motion of red cells over the endothelial surface layer (ESL). The experimental setup consists of a running conveyer belt covered with a porous sheet, and an upper planar board, i.e. planing surface. The pore pressure generation was captured when the planing surface glides over the porous sheet. If the lateral leakage was eliminated, we found that the overall pore pressure's contribution to the total lift, fair 80%, and the friction coefficient η = 0.0981, when U =5 m/s, L =0.381 m, λ = h2/h0 = 1 and k =h2/h1 = 3, where U is the velocity of the conveyor belt; L is the planing surface length; h0, h1 and h2 are the undeformed, leading and trailing edge porous layer thickness, respectively. fair increases with the increase in U, λ and L, while decreases with the increase in k. η decreases with the increase in fair. If lateral pressure leakage exists, the pore pressure generation is reduced by nearly 90%. All the results agreed well with the theoretical predictions. The study here lays the foundation for applying soft porous media for new type of bearing with significantly reduced friction. This research was supported by the National Science Foundation (NSF CBET) under Award No. 1511096.

  16. Radioassay for serum and red cell folate

    International Nuclear Information System (INIS)

    Longo, D.L.; Herbert, V.

    1976-01-01

    A simple, reliable assay for serum and red cell folate is described. It uses plain untreated liquid or powdered milk, requiring no special handling or purification, as binder. Such milk makes it possible to ignore endogenous serum folate binder, since crude (but not purified) milk contains a factor which releases folate from serum binder. It simplifies counting radioactivity by employing a gamma emitting isotope of pteroylglutamic acid (PGA), namely the 125 I-tyramide of PGA. Like the 3 H-PGA assay of Givas and Gutcho, it permits the use of stable PGA rather than unstable methyltetrahydrofolic acid (MeTHFA) standards, because it is carried out at pH 9.3, a pH at which milk folate binder is unable to distinguish PGA from MeTHFA, which is the predominant folate in human tissues. The equipment required to do the radioassay is present in most diagnostic chemistry laboratories. Results are essentially identical to the generally accepted Lactobacillus casei microbiologic method of folate assay, except that false low results are not produced in the radioassay by antibiotics, tranquilizers, and chemotherapeutic agents. Three caveats in its use are the relative instability of 125 I-PGA as compared to 3 H-PGA, the fact that various powdered milks differ widely in folate-binding capacity, and that only about 60 percent of commercially obtained skim or powdered milk preparations appear to contain the substance which splits folate from serum binder

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research that ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  18. 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 ...

  19. 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.

  20. Red cell ferritin and iron stores in chronic granulocytic leukemia

    International Nuclear Information System (INIS)

    Cermak, J.; Neuwirth, J.; Voglova, J.; Brabec, V.; Chrobak, L.

    1994-01-01

    Basic red cell ferritin was investigated in 28 patients with different phases of chronic granulocytic leukemia (GCL). Red cell ferritin was significantly decreased in remission after busulphan treatment and significantly elevated in the blast crisis as compared to healthy controls. Bone marrow stainable iron was decreased or absent in 86% of patients in the initial phase at the time of diagnosis and in 92% of those in remission. Red cell ferritin correlated with serum ferritin, however, serum ferritin level remained above normal range during all phases of the disease. A negative correlation between red cell ferritin and hemoglobin (Hb) (r = -0.605, p < 0.001) suggested that red cell ferritin level reflected the rate of iron utilization for heme synthesis. Decrease red cell iron observed in the remission may be explained by regression of dyserythropoiesis and by restoration of normal Hb synthesis after busulphan treatment. A progressive dyserythropoiesis in the blast crisis may lead to an increased red cell ferritin level. (author)

  1. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

    DEFF Research Database (Denmark)

    Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham

    2009-01-01

    OBJECTIVES: Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed...... of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...

  2. High-resolution spectra of stars in globular clusters. VI - Oxygen-deficient red giant stars in M13

    International Nuclear Information System (INIS)

    Brown, J.A.; Wallerstein, G.; Oke, J.B.

    1991-01-01

    From high-resolution, high signal-to-noise spectra, abundances of carbon, nitrogen, and oxygen and the C-12/C-13 ratio for five red giants in M13, including star II-67, which has previously been reported to be deficient in oxygen have been determined. Three of the five stars exhibit substantial oxygen deficiencies; O/Fe values range from +0.5 to less than about 0.3. The sum of the CNO nuclides is the same for all stars, which is interpreted as evidence that mixing of CNO-cycled material into the envelope is the cause of the variations in oxygen abundance. 41 refs

  3. Effects of helicopter transport on red blood cell components

    Science.gov (United States)

    Otani, Taiichi; Oki, Ken-ichi; Akino, Mitsuaki; Tamura, Satoru; Naito, Yuki; Homma, Chihiro; Ikeda, Hisami; Sumita, Shinzou

    2012-01-01

    Background There are no reported studies on whether a helicopter flight affects the quality and shelf-life of red blood cells stored in mannitol-adenine-phosphate. Materials and methods Seven days after donation, five aliquots of red blood cells from five donors were packed into an SS-BOX-110 container which can maintain the temperature inside the container between 2 °C and 6 °C with two frozen coolants. The temperature of an included dummy blood bag was monitored. After the box had been transported in a helicopter for 4 hours, the red blood cells were stored again and their quality evaluated at day 7 (just after the flight), 14, 21 and 42 after donation. Red blood cell quality was evaluated by measuring adenosine triphosphate, 2,3-diphosphoglycerate, and supernatant potassium, as well as haematocrit, intracellular pH, glucose, supernatant haemoglobin, and haemolysis rate at the various time points. Results During the experiment the recorded temperature remained between 2 and 6 °C. All data from the red blood cells that had undergone helicopter transportation were the same as those from a control group of red blood cell samples 7 (just after the flight), 14, 21, and 42 days after the donation. Only supernatant Hb and haemolysis rate 42 days after the donation were slightly increased in the helicopter-transported group of red blood cell samples. All other parameters at 42 days after donation were the same in the two groups of red blood cells. Discussion These results suggest that red blood cells stored in mannitol-adenine-phosphate are not significantly affected by helicopter transportation. The differences in haemolysis by the end of storage were small and probably not of clinical significance. PMID:22153688

  4. Effects of helicopter transport on red blood cell components.

    Science.gov (United States)

    Otani, Taiichi; Oki, Ken-ichi; Akino, Mitsuaki; Tamura, Satoru; Naito, Yuki; Homma, Chihiro; Ikeda, Hisami; Sumita, Shinzou

    2012-01-01

    There are no reported studies on whether a helicopter flight affects the quality and shelf-life of red blood cells stored in mannitol-adenine-phosphate. Seven days after donation, five aliquots of red blood cells from five donors were packed into an SS-BOX-110 container which can maintain the temperature inside the container between 2 °C and 6 °C with two frozen coolants. The temperature of an included dummy blood bag was monitored. After the box had been transported in a helicopter for 4 hours, the red blood cells were stored again and their quality evaluated at day 7 (just after the flight), 14, 21 and 42 after donation. Red blood cell quality was evaluated by measuring adenosine triphosphate, 2,3-diphosphoglycerate, and supernatant potassium, as well as haematocrit, intracellular pH, glucose, supernatant haemoglobin, and haemolysis rate at the various time points. During the experiment the recorded temperature remained between 2 and 6 °C. All data from the red blood cells that had undergone helicopter transportation were the same as those from a control group of red blood cell samples 7 (just after the flight), 14, 21, and 42 days after the donation. Only supernatant Hb and haemolysis rate 42 days after the donation were slightly increased in the helicopter-transported group of red blood cell samples. All other parameters at 42 days after donation were the same in the two groups of red blood cells. These results suggest that red blood cells stored in mannitol-adenine-phosphate are not significantly affected by helicopter transportation. The differences in haemolysis by the end of storage were small and probably not of clinical significance.

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

    Science.gov (United States)

    Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M; Schonbrun, Ethan

    2015-08-11

    Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they 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 Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability.

  6. Reduction in unnecessary red blood cell folate testing by restricting computerized physician order entry in the electronic health record.

    Science.gov (United States)

    MacMillan, Thomas E; Gudgeon, Patrick; Yip, Paul M; Cavalcanti, Rodrigo B

    2018-05-02

    Red blood cell folate is a laboratory test with limited clinical utility. Previous attempts to reduce physician ordering of unnecessary laboratory tests, including folate, have resulted in only modest success. The objective of this study was to assess the effectiveness and impacts of restricting red blood cell folate ordering in the electronic health record. This was a retrospective observational study from January 2010 to December 2016 at a large academic healthcare network in Toronto, Canada. All inpatients and outpatients who underwent at least 1 red blood cell folate or vitamin B12 test during the study period were included. Red blood cell folate ordering was restricted to clincians in gastroenterology and hematology and was removed from other physicians' computerized order entry screen in the electronic health record in June 2013. Red blood cell folate testing decreased by 94.4% during the study, from a mean of 493.0 (SD 48.0) tests/month before intervention to 27.6 (SD 10.3) tests/month after intervention (P<.001). Restricting red blood cell folate ordering in the electronic health record resulted in a large and sustained reduction in red blood cell folate testing. Significant cost savings estimated at over a quarter-million dollars (CAD) over three years were achieved. There was no significant clinical impact of the intervention on the diagnosis of folate deficiency. Copyright © 2018. Published by Elsevier Inc.

  7. Red blood cell transfusion in neurosurgery.

    Science.gov (United States)

    Linsler, Stefan; Ketter, Ralf; Eichler, Hermann; Schwerdtfeger, Karsten; Steudel, Wolf-Ingo; Oertel, Joachim

    2012-07-01

    The necessity of red blood cell (RBC) transfusions in neurosurgical procedures is under debate. Although detailed recommendations exist for many other surgical disciplines, there are very limited data on the probability of transfusions during neurosurgical procedures. Three-thousand and twenty-six consecutive adult patients undergoing neurosurgical procedures at Saarland University Hospital from December 2006 to June 2008 were retrospectively analyzed for administration of RBCs. The patients were grouped into 11 main diagnostic categories for analysis. The transfusion probability and cross-match to transfusion ratio (C/T ratio) were calculated. Overall, the transfusion probability for neurosurgical procedures was 1.7 % (52/3,026). The probability was 6.5 % for acute subdural hematoma (7/108), 6.2 % for spinal tumors (5/80), 4.6 % for intracerebral hemorrhage (ICH, 4/98), 2.8 % for abscess (3/108), 2.4 % for traumatic brain injury (4/162), 2.3 % for cerebral ischemia (1/44), 1.9 % for subarachnoid hemorrhage (SAH) /aneurysms (4/206), 1.4 % for brain tumors (10/718), 0.8 % for hydrocephalus (2/196), 0.4 % for degenerative diseases of the spine (5/1290), including 3.6 % (3/82) for posterior lumbar interbody fusion (PLIF) and 0 % for epidural hematoma (0/15). The transfusion probabilities for clipping and coiling of SAH were 2.9 % (2/68) and 1.7 % (2/120) respectively. The probability of blood transfusion during neurosurgical procedures is well below the 10 % level which is generally defined as the limit for preoperative appropriation of RBCs. Patients with spinal tumors, acute subdural hematomas or ICH, i.e., patients undergoing large decompressive procedures of bone or soft tissue, had a higher probability of transfusion.

  8. Red mold rice promoted antioxidase activity against oxidative injury and improved the memory ability of zinc-deficient rats.

    Science.gov (United States)

    Lee, Bao-Hong; Ho, Bing-Ying; Wang, Chin-Thin; Pan, Tzu-Ming

    2009-11-25

    Zn deficiency is a common disease leading to memory impairment with increasing age. This study evaluated the protection effects of red mold rice (RMR) administration and Zn supplementation against memory and learning ability impairments from oxidative stress caused by Zn deficiency. Rats (4 weeks old) were induced to be Zn deficiency by a Zn-deficient diet for 12 weeks. After that, rats were administered Zn, 1xRMR, 5xRMR, and various dosages of RMR plus Zn, respectively. Decreases of antioxidant enzyme activities in the hippocampus and cortex were observed, and the levels of Ca, Fe, and Mg were increased in the hippocampus and cortex of Zn-deficient rats, leading to memory and learning ability injury. However, the administration of RMR (1- or 5-fold dosage) and with or without Zn significantly improved the antioxidase and neural activity to maintain cortex and hippocampus functions. This study demonstrates that RMR is a possible functional food for the prevention or cure of neural injury associated with Zn deficiency.

  9. Progranulin deficiency causes the retinal ganglion cell loss during development.

    Science.gov (United States)

    Kuse, Yoshiki; Tsuruma, Kazuhiro; Mizoguchi, Takahiro; Shimazawa, Masamitsu; Hara, Hideaki

    2017-05-10

    Astrocytes are glial cells that support and protect neurons in the central nervous systems including the retina. Retinal ganglion cells (RGCs) are in contact with the astrocytes and our earlier findings showed the reduction of the number of cells in the ganglion cell layer in adult progranulin deficient mice. In the present study, we focused on the time of activation of the astrocytes and the alterations in the number of RGCs in the retina and optic nerve in progranulin deficient mice. Our findings showed that the number of Brn3a-positive cells was reduced and the expression of glial fibrillary acidic protein (GFAP) was increased in progranulin deficient mice. The progranulin deficient mice had a high expression of GFAP on postnatal day 9 (P9) but not on postnatal day 1. These mice also had a decrease in the number of the Brn3a-positive cells on P9. Taken together, these findings indicate that the absence of progranulin can affect the survival of RGCs subsequent the activation of astrocytes during retinal development.

  10. Red cell survival and sequestration in acute intermittent porphyria

    International Nuclear Information System (INIS)

    Nawalkha, P.L.; Soni, S.G.; Agrawal, V.K.; Misra, S.N.

    1980-01-01

    Life span and sequestration of red cells have been studied in twenty one proved cases of acute intermittent porphyria of different age and sex group from Bikaner District, Rajasthan State (India). Chromium-51 labelled red cells were used in the study and the excess count method of Bughe Jones and Szur was used to calculate the index of sequestration. The mean apparent half survival time of erythrocytes in the control subjects was 25.9 +- 2.9 (S.D.) days and the same in the prophyria patients was 27.0 +- 3.8 days. This shows that the life span of red cells is normal in both the patient and the control. Excess destruction of red blood cells was found to take place in either spleen or liver in the disease and no excess accumulation of erythrocytes occurred over spleen as compared to liver. (M.G.B.)

  11. 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...... differences with 95% confidence intervals. RESULTS: 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean...... were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion...

  12. 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.

  13. Deficient natural killer cell function in preeclampsia

    International Nuclear Information System (INIS)

    Alanen, A.; Lassila, O.

    1982-01-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour 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

  14. The Effect of Shape Memory on Red Blood Cell Motions

    Science.gov (United States)

    Niu, Xiting; Shi, Lingling; Pan, Tsorng-Whay; Glowinski, Roland

    2013-11-01

    An elastic spring model is applied to study the effect of the shape memory on the motion of red blood cell in flows. In shear flow, shape memory also plays an important role to obtain all three motions: tumbling, swinging, and tank-treading. In Poiseuille flow, cell has an equilibrium shape as a slipper or parachute depending on capillary number. To ensure the tank-treading motion while in slippery shape, a modified model is proposed by introducing a shape memory coefficient which describes the degree of shape memory in cells. The effect of the coefficient on the cell motion of red blood cell will be presented.

  15. Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

    Science.gov (United States)

    Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

    2015-01-01

    Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

  16. Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

    Science.gov (United States)

    Ayars, Michael; Eshleman, James; Goggins, Michael

    2017-05-19

    Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.

  17. Certain Red Blood Cell Indices of Maternal and Umbilical Cord ...

    African Journals Online (AJOL)

    Uche

    Background: Umbilical cord blood analysis may give a clue to the state of health of both pregnant mothers and their neonates. However ... Keywords: Umbilical cord blood; maternal blood; haemoglobin concentration; packed cell volume; red cell indices. Received on .... The packed cell volume was measured using the.

  18. In vivo red blood cell compatibility testing using indium-113m tropolone-labeled red blood cells

    International Nuclear Information System (INIS)

    Morrissey, G.J.; Gravelle, D.; Dietz, G.; Driedger, A.A.; King, M.; Cradduck, T.D.

    1988-01-01

    In vivo radionuclide crossmatch is a method for identifying compatible blood for transfusion when allo- or autoantibodies preclude the use of conventional crossmatching techniques. A technique for labeling small volumes of donor red blood cells with [/sup 113m/In]tropolone is reported. The use of /sup 113m/In minimizes the accumulation of background radioactivity and the radiation dose especially so when multiple crossmatches are performed. Labeling red cells with [/sup 113m/In]tropolone is faster and easier to perform than with other radionuclides. Consistently high labeling efficiencies are obtained and minimal /sup 113m/In activity elutes from the labeled red blood cells. A case study involving 22 crossmatches is presented to demonstrate the technique. The radiation dose equivalent from /sup 113m/In is significantly less than with other radionuclides that may be used to label red cells

  19. 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.

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

    International Nuclear Information System (INIS)

    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

  1. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  2. Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

    Science.gov (United States)

    2014-11-01

    increased by hydroxyurea, ATR inhibition, deregulated c-Myc expression and by PARPi treatment of BRCA1 deficient cells. This work was recently published...Genome Stability." 6: May 27, 2013-Collaborative Research Center 655 from Cells to Tissues seminar series at the Max-Planck-Institute in Dresden, Germany ...Eisenach, Germany -“Genome Stability during DNA Replication” 8: May 3, 2013- Chemical and Systems Biology Department Seminar Series at Stanford

  3. Red blood cell dynamics: from cell deformation to ATP release.

    Science.gov (United States)

    Wan, Jiandi; Forsyth, Alison M; Stone, Howard A

    2011-10-01

    The mechanisms of red blood cell (RBC) deformation under both static and dynamic, i.e., flow, conditions have been studied extensively since the mid 1960s. Deformation-induced biochemical reactions and possible signaling in RBCs, however, were proposed only fifteen years ago. Therefore, the fundamental relationship between RBC deformation and cellular signaling dynamics i.e., mechanotransduction, remains incompletely understood. Quantitative understanding of the mechanotransductive pathways in RBCs requires integrative studies of physical models of RBC deformation and cellular biochemical reactions. In this article we review the physical models of RBC deformation, spanning from continuum membrane mechanics to cellular skeleton dynamics under both static and flow conditions, and elaborate the mechanistic links involved in deformation-induced ATP release. This journal is © The Royal Society of Chemistry 2011

  4. 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

  5. Freeze-Dried Human Red Blood Cells

    Science.gov (United States)

    1992-04-15

    period in the liquid state. 2. The levels of glycolytic intermediates (ATP, adenosine 5’triphosphate; 2,3-DPG 2, 3- diphosphoglycerate ) in rehydrated...8217 diphosphate, ADP; adenosine 5 monophosphate, AMP; 2,3- diphosphoglycerate . 2.3-DPG and lactate: (2) measurement of cell indices (mean cell volume (MCV), mean...monophosphate: 2,3-DPG. 2.3- diphosphoglycerate : MCV. Mean Cell Volume: MCH, Mean Cell Hemoglobin: MCHC, Mean Cell Hemoglobin Concentrations. ** Lactate levels

  6. 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.

  7. Consequences of dysregulated complement regulators on red blood cells

    NARCIS (Netherlands)

    Thielen, Astrid J. F.; Zeerleder, Sacha; Wouters, Diana

    2018-01-01

    The complement system represents the first line of defense that is involved in the clearance of pathogens, dying cells and immune complexes via opsonization, induction of an inflammatory response and the formation of a lytic pore. Red blood cells (RBCs) are very important for the delivery of oxygen

  8. Reflection coefficients of permeant molecules in human red cell suspensions.

    Science.gov (United States)

    Owen, J D; Eyring, E M

    1975-08-01

    The Staverman reflection coefficient, sigma for several permeant molecules was determined in human red cell suspensions with a Durrum stopped-flow spectrophotometer. This procedure was first used with dog, cat, and beef red cells and with human red cells. The stopped-flow technique used was similar to the rapid-flow method used by those who originally reported sigma measurements in human red cells for molecules which rapidly penetrate the red cell membrane. The sigma values we obtained agreed with those previously reported for most of the slow penetrants, except malonamide, but disagreed with all the sigma values previously reported for the rapid penetrants. We were unable to calculate an "equivalent pore radius" with our sigma data. The advantages of our equipment and our experimental procedure are discussed. Our sigma data suggest that sigma is indirectly proportional to the log of the nonelectrolyte permeability coefficient, omega. Since a similar trend has been previously shown for log omega and molar volume of the permeant molecules, a correlatioo was shown between sigma and molar volume suggesting the membrane acts as a sieve.

  9. Radioprotective effect of cysteamine in glutathione synthetase-deficient cells

    International Nuclear Information System (INIS)

    Deschavanne, P.J.; Debieu, D.; Malaise, E.P.; Midander, J.; Revesz, L.

    1986-01-01

    The radioprotective role of endogenous and exogenous thiols was investigated, with survival as the end-point, after radiation exposure of cells under oxic and hypoxic conditions. Human cell strains originating from a 5-oxoprolinuria patient and from a related control were used. Due to a genetic deficiency in glutathione synthetase, the level of free SH groups, and in particular that of glutathione, is decreased in 5-oxoprolinuria cells. The glutathione synthetase deficient cells have a reduced oxygen enhancement ratio (1.5) compared to control cells (2.7). The radiosensitivity was assessed for both cell strains in the presence of different concentrations of an exogenous radioprotector:cysteamine. At concentrations varying between 0.1 and 20 mM, cysteamine protected the two cell strains to the same extent when irradiated under oxic and hypoxic conditions. The protective effect of cysteamine was lower under hypoxia than under oxic conditions for both cell strains. Consequently, the oxygen enhancement ratio decreased for both cell strains when cysteamine concentration increased. These results suggest that cysteamine cannot replace endogenous thiols as far as they are implicated in the radiobiological oxygen effect. (author)

  10. Evidence that cell surface charge reduction modifes capillary red cell velocity-flux relationships in hamster cremaster muscle

    NARCIS (Netherlands)

    Vink, H.; Wieringa, P. A.; Spaan, J. A.

    1995-01-01

    1. From capillary red cell velocity (V)-flux (F) relationships of hamster cremaster muscle a yield velocity (VF = 0) can be derived at which red cell flux is zero. Red cell velocity becomes intermittent and/or red blood cells come to a complete standstill for velocities close to this yield velocity,

  11. Radiation-induced mitotic catastrophe in PARG-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Ame, J.Ch.; Fouquerel, E.; Dantzer, F.; De Murcia, G.; Schreiber, V. [IREBS-FRE3211 du CNRS, Universite de Strasbourg, ESBS, Bd Sebastien Brant, BP 10413, 67412 Illkirch Cedex (France); Gauthier, L.R.; Boussin, F.D. [Laboratoire de Radiopathologie/INSERM U967, CEA-DSV-IRCM, 92265 Fontenay aux Roses, Cedex 6 (France); Biard, D. [CEA-DSV-IRCM/INSERM U935, Institut A. Lwoff-CNRS, BP 8, 94801 Villejuif cedex (France)

    2009-07-01

    Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in the regulation of chromatin structure, DNA metabolism, cell division and cell death. Through the hydrolysis of poly(ADP-ribose) (PAR), Poly(ADP-ribose) glyco-hydrolase (PARG) has a crucial role in the control of life-and-death balance following DNA insult. Comprehension of PARG function has been hindered by the existence of many PARG isoforms encoded by a single gene and displaying various subcellular localizations. To gain insight into the function of PARG in response to irradiation, we constitutively and stably knocked down expression of PARG isoforms in HeLa cells. PARG depletion leading to PAR accumulation was not deleterious to undamaged cells and was in fact rather beneficial, because it protected cells from spontaneous single-strand breaks and telomeric abnormalities. By contrast, PARG-deficient cells showed increased radiosensitivity, caused by defects in the repair of single- and double-strand breaks and in mitotic spindle checkpoint, leading to alteration of progression of mitosis. Irradiated PARG-deficient cells displayed centrosome amplification leading to mitotic supernumerary spindle poles, and accumulated aberrant mitotic figures, which induced either polyploidy or cell death by mitotic catastrophe. Our results suggest that PARG could be a novel potential therapeutic target for radiotherapy. (authors)

  12. 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....... The absence of the initiation cascade in Dam- cells is proposed to account for this observation of apparent incompatibility between plasmid and chromosomal copies of oriC. Studies using oriC-pBR322 chimeric plasmids and their deletion derivatives indicated that the incompatibility determinant is an intact...

  13. 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.

  14. Diagnostic significance of red cell indices in beta-thalassaemia trait

    International Nuclear Information System (INIS)

    Hussain, Z.; Malik, N.; Chughtai, A.S.

    2005-01-01

    The purpose of this study was to evaluate the formulae for the diagnosis of beta-thalassemia trait cases in settings where electrophoreses is not available. The study included 50 cases of beta-thalassaemia trait already diagnosed by Hb electrophoresis. CBC samples were analyzed on Sysmex K4500 and red cell indices were used to evaluate formulae for differentiating beta thalassaemia trait from iron deficiency anemia. The formula MCV/RBC and MCH/RBC identified 56% of the cases. Formula MCV - (5 x Hb)- RBC - 8.4 identified 54% of beta thalassemia trait cases. The formula MCV x MCH identified 92% of cases. RBC indices given by 100 electronic counters can be used to differentiate iron deficiency anemia from beta-thalassaemia trait at least provisionally in areas where Hb electrophoresis is not available. (author)

  15. In vivo red cell destruction by anti-Lu6

    International Nuclear Information System (INIS)

    Issitt, P.D.; Valinsky, J.E.; Marsh, W.L.; DiNapoli, J.; Gutgsell, N.S.

    1990-01-01

    An example is presented of an IgG1, anti-Lu6, that reacted by indirect antiglobulin test and was capable of destroying antigen-positive red cells in vivo. Two methods for the measurement of red cell survival, 51 Cr labeling and flow cytometry, gave the same result: 20 percent of the test dose of Lu:6 red cells was destroyed in the first hour after injection and 80 percent in the first 24 hours. The clinical relevance of the antibody was correctly predicted by an in vitro monocyte monolayer assay. The finding that this example of anti-Lu6 was clinically significant should not be taken to mean that all antibodies directed against high-incidence Lutheran and Lutheran system-related antigens will behave similarly. When such antibodies are encountered, in vivo and/or in vitro studies to assess their clinical significance are necessary before rare blood is used for transfusion

  16. Sup(99m) Technetium - labeled red blood cells 'in vitro'

    International Nuclear Information System (INIS)

    Bernardo Filho, M.; Souza Moura, I.N. de; Boasquevisque, E.M.

    1983-01-01

    A simple technique for the preparation of sup(99m) Tc labeled red blood cells using a comercial kit is described. To each 3ml of plain blood with anti-coagulant was added 1ml of solution of commercial kit with 6.8 μg of stannous chloride. This mixture was incubated in water bath, at 37 0 C, for 60 minutes. Then technetium-99m was added and the mixture was left for another ten minutes, in water bath, at 37 0 C. Under these conditions there was the best labeling of the red blood cells. Similar results were obtained with a solution of stannous chloride prepared freshly. The labeling is strong for 6.8 μg stannous chloride because the labeling was not removed by the several washes of the red blood cells or by the left in water bath. (Author) [pt

  17. Techniques for measuring red cell, platelet, and WBC survival

    International Nuclear Information System (INIS)

    Mayer, K.; Freeman, J.E.

    1986-01-01

    Blood cell survival studies yield valuable information concerning production and destruction of cells circulating in the bloodstream. Methodologies for the measurement of red cell survival include nonisotopic methods such as differential agglutination and hemolysis. The isotopic label may be radioactive or, if not, will require availability of a mass spectrograph. These methods fall into two categories, one where red cells of all ages are labeled ( 51 Cr, DFP32, etc.) and those employing a cohort label of newly formed cells ( 14 C glycine, 75 Se methionine, etc.). Interpretation of results for methodology employed and mechanism of destruction, random or by senescence, are discussed. A similar approach is presented for platelet and leukocyte survival studies. The inherent difficulties and complications of sequestration, storage, and margination of these cells are emphasized and discussed. 38 references

  18. Labelling of red blood cells with 99m pertechnetate

    International Nuclear Information System (INIS)

    Vyth, A.; Raam, C.F.

    1979-07-01

    This paper describes a method for labelling red blood cells with 99mTc in vitro, using electrolytically generated stannous ions as the reducing agent for 99mTc-pertechnetate. A labelling of 95% was found. A method for the in vivo labelling of red blood cells is also reported. This involves an injection of a stanno-DTPA-complex followed 20 minutes later by a 99mTc-pertechnetate solution scintillation camera images show more background activity when the in vivo method of labelling is used

  19. 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.

  20. Red cells with paroxysmal nocturnal hemoglobinuria-phenotype in patients with acute leukemia.

    Science.gov (United States)

    Meletis, John; Terpos, Evangelos; Samarkos, Michalis; Meletis, Christos; Apostolidou, Effie; Komninaka, Veroniki; Anargyrou, Konstantinos; Korovesis, Konstantinos; Mavrogianni, Despina; Variami, Eleni; Viniou, Nora; Konstantopoulos, Konstantinos

    2002-04-01

    CD55 and CD59 are complement regulatory proteins that are linked to the cell membrane via a glycosyl-phosphatidylinositol anchor. They are reduced mainly in paroxysmal nocturnal hemoglobinuria (PNH) and in other hematological disorders. However, there are very few reports in the literature concerning their expression in patients with acute leukemias (AL). We studied the CD55 and CD59 expression in 88 newly diagnosed patients with AL [65 with acute non-lymphoblastic leukemia (ANLL) and 23 with acute lymphoblastic leukemia (ALL)] using the sephacryl gel test, the Ham and sucrose lysis tests and we compared the results with patients' clinical data and disease course. Eight patients with PNH were also studied as controls. Red cell populations deficient in both CD55 and CD59 were detected in 23% of ANLL patients (especially of M(0), M(2) and M(6) FAB subtypes), 13% of ALL and in all PNH patients. CD55-deficient erythrocytes were found in 6 ANLL patients while the expression of CD59 was decreased in only 3 patients with ANLL. No ALL patient had an isolated deficiency of these antigens. There was no correlation between the existence of CD55 and/or CD59 deficiency and the percentage of bone marrow infiltration, karyotype or response to treatment. However no patient with M(3), M(5), M(7) subtype of ANLL and mature B- or T-cell ALL showed a reduced expression of both antigens. The deficient populations showed no alteration after chemotherapy treatment or during disease course. This study provides evidence about the lower expression of CD55 and CD59 in some AL patients and the correlation with their clinical data. The possible mechanisms and the significance of this phenotype are discussed.

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

    African Journals Online (AJOL)

    INTRODUCTION: Despite several documented challenges, Hematopoietic Stem cell Transplantation (HSCT) remains the only curative therapy for Sickle Cell Disease (SCD). However HSCT is expensive with its complications, therefore supportive care remains the main available option to many Nigerians. Frequent blood ...

  2. In vivo studies of the long-term 51Cr red cell survival of serologically incompatible red cell units

    International Nuclear Information System (INIS)

    Baldwin, M.L.; Ness, P.M.; Barrasso, C.; Kickler, T.S.; Drew, H.; Tsan, M.F.; Shirey, R.S.

    1985-01-01

    The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of 51 Cr-labeled incompatible red cells was measured over 1 hour. After demonstrating that the 1-hour survival times were successful (greater than 70%), each patient then received 5 ml of the same 51 Cr-labeled red cells followed by the transfusion of the remainder of the red cell unit. The long-term T 1/2Cr survival for each case was patient 1 (anti-McCa), 15 days; patient 2 (anti-JMH), 12 days; patient 3 (anti-Kna), 31 days; patient 4 (anti-McCa), 12 days; and patient 5 (anti-Hya), 14 days. Each antibody tested in an in vitro homologous macrophage assay showed less than 5 percent phagocytosis. Anti-JMH was the only antibody to react with IgG subclass antisera and was determined to be IgG4. The macrophage assay, IgG subclass testing, and short-term (1 hour, 1 ml) 51 Cr survival studies all indicated that the short-term survival was good. However, only the measurement of long-term survival with transfused units of serologically incompatible red cells was able to determine the actual survival, and clinical significance of the alloantibodies. Determining the actual long-term survival by the method described here can be of importance for patients requiring chronic red cell transfusion

  3. HepG2 cells develop signs of riboflavin deficiency within four days of culture in riboflavin-deficient medium*

    OpenAIRE

    Werner, Ricarda; Manthey, Karoline C.; Griffin, Jacob B.; Zempleni, Janos

    2005-01-01

    Flavin mononucleotide and flavin adenine dinucleotide are essential coenzymes in redox reactions. For example, flavin adenine dinucleotide is a coenzyme for both glutathione reductase and enzymes that mediate the oxidative folding of secretory proteins. Here we investigated short-term effects of moderately riboflavin-deficient culture medium on flavin-related responses in HepG2 hepatocarcinoma cells. Cells were cultured in riboflavin-deficient (3.1 nmol/L) medium for up to six days; controls ...

  4. Pure red cell aplasia following irradiation of an asymptomatic thymoma

    International Nuclear Information System (INIS)

    Shibata, Kazuo; Masaoka, Akira; Mizuno, Takeo; Ichimura, Hideki

    1982-01-01

    An unusual case of pure red-cell aplasia (PRCA) developed sixteen days after irradiation of an asymptomatic thymoma. After removal of the encapsulated thymoma there was no improvement in the anemia, and no response to adrenocortical and anabolic steroid hormones or immunosuppressive agents. (author)

  5. Detection of pulmonary hemorrhage with technetium-labeled red cells

    International Nuclear Information System (INIS)

    Winzelberg, G.G.; Laman, D.; Sachs, M.; Miller, W.H.

    1981-01-01

    Noninvasive techniques to aid in the diagnosis of massive pulmonary hemoptysis would be helpful in guiding more-invasive procedures such as bronchial artery angiography, which carries a risk of transverse myelitis. A patient was studied with technetium-labeled red cells and successfully detected a site of intermittent hemorrhage from the lung

  6. 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

  7. 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 this techno...

  8. 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

  9. Characteristic point algorithm in laser ektacytometry of red blood cells

    Science.gov (United States)

    Nikitin, S. Yu.; Ustinov, V. D.

    2018-01-01

    We consider the problem of measuring red blood cell deformability by laser diffractometry in shear flow (ektacytometry). A new equation is derived that relates the parameters of the diffraction pattern to the width of the erythrocyte deformability distribution. The numerical simulation method shows that this equation provides a higher accuracy of measurements in comparison with the analogous equation obtained by us earlier.

  10. 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 alloimmuniz...

  11. 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....

  12. 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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

  13. Frequency and specificity of red blood cell alloantibodies among ...

    African Journals Online (AJOL)

    Background: Blood transfusion usually results in production of alloantibody against one or more foreign red blood cell antigens which may complicate subsequent transfusions. The probability of alloimmunization depends on number and frequency of transfusion, antigen immunogenicity, recipient immune response and ...

  14. Evaluation of red blood cell stability during immersion blood warming

    African Journals Online (AJOL)

    Introduction: The practice of warming blood for transfusion by immersion into a waterbath has been investigated. Objective: To find the maximum waterbath temperature at which blood can be heated effectively without effecting the red blood cell functional and structural integrity. Method: Blood, three days after donation ...

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

    NARCIS (Netherlands)

    Hogman, CF; Meryman, HT

    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

  16. Assessment of Red Blood Cell Parameters and Peripheral Smear at ...

    African Journals Online (AJOL)

    Cold agglutination disease (CAD) is characterized by an auto‑antibody which is able to agglutinate red blood cells (RBCs) at temperatures lower than that of the body, and subsequently to activate the complement system responsible for lysis of RBCs. Patients show hemolytic anemia of varying degrees of severity, which ...

  17. Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery

    DEFF Research Database (Denmark)

    Mazer, C David; Whitlock, Richard P; Fergusson, Dean A

    2017-01-01

    BACKGROUND: The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS: In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a E...

  18. Risk of red blood cell alloimmunisation in Rwanda: Assessment of ...

    African Journals Online (AJOL)

    Background: Screening of alloantibodies in patients is not yet done in district hospitals of Rwanda. The practice is to transfuse ABO/D compatible blood following an immediate spin crossmatch (IS-XM) or indirect antiglobulin test crossmatch (IAT-XM). Objectives: To assess the risk of red blood cell (RBC) alloimmunisation ...

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

    NARCIS (Netherlands)

    de Back, Djuna Z.; Kostova, Elena B.; van Kraaij, Marian; van den Berg, Timo K.; van Bruggen, Robin

    2014-01-01

    Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 10(10) RBC are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with

  20. 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.

  1. Margination of Stiffened Red Blood Cells Regulated By Vessel Geometry.

    Science.gov (United States)

    Chen, Yuanyuan; Li, Donghai; Li, Yongjian; Wan, Jiandi; Li, Jiang; Chen, Haosheng

    2017-11-10

    Margination of stiffened red blood cells has been implicated in many vascular diseases. Here, we report the margination of stiffened RBCs in vivo, and reveal the crucial role of the vessel geometry in the margination by calculations when the blood is seen as viscoelastic fluid. The vessel-geometry-regulated margination is then confirmed by in vitro experiments in microfluidic devices, and it establishes new insights to cell sorting technology and artificial blood vessel fabrication.

  2. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line

    International Nuclear Information System (INIS)

    Terasaki, Takeo; Shimosato, Yukio; Wada, Makio; Yokota, Jun; Terada, Masaaki

    1990-01-01

    Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line. (author)

  4. Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood cells.

    Science.gov (United States)

    Birgegård, G; Sandhagen, B

    2001-01-01

    Some patients experience an improved well-being during treatment with recombinant human erythropoietin even with an unchanged Hb level. We have hypothesized that this may not be only a placebo effect. 2,3-diphosphoglycerate (2,3-DPG) in red blood cells increases in response to anaemia/hypoxia and causes a shift of the oxygen dissociation curve, allowing a more effective oxygen delivery. We have investigated red cell 2,3-DPG concentrations during erythropoietin treatment in healthy volunteers as a mediator of a possible physiological explanation. Thirteen healthy subjects with no iron deficiency were recruited and randomly assigned to a treatment group comprising five males and three females and a control group including three males and two females. The treatment group was treated with erythropoietin (Recormon), 20 IE/kg subcutaneously three times/week for 4 weeks. Blood samples were collected at each injection day and 10 days after the last injection and at corresponding times in the control group. B-Hb, red cell 2,3-DPG and P50 were measured by standard techniques and oxygen-releasing capacity was calculated. due to the sampling (26 ml each time, three times/week) the mean Hb level was lowered from 140.5 +/- 5.9 to 128.6 +/- 10.4 g/L in the control group whereas the erythropoietin treatment group maintained a mean Hb level of about 142 g/L (plevel curve as well as that for oxygen releasing capacity also differed significantly between the two groups (p levels. treatment with erythropoietin causes an increase in red cell 2,3-DPG levels.

  5. Noncytotoxic orange and red/green derivatives of DsRed-Express2 for whole-cell labeling

    Directory of Open Access Journals (Sweden)

    Glick Benjamin S

    2009-04-01

    Full Text Available Abstract Background Whole-cell labeling is a common application of fluorescent proteins (FPs, but many red and orange FPs exhibit cytotoxicity that limits their use as whole-cell labels. Recently, a tetrameric red FP called DsRed-Express2 was engineered for enhanced solubility and was shown to be noncytotoxic in bacterial and mammalian cells. Our goal was to create derivatives of this protein with different spectral properties. Results Building on previous studies of DsRed mutants, we created two DsRed-Express2 derivatives: E2-Orange, an orange FP, and E2-Red/Green, a dual-color FP with both red and green emission. We show that these new FPs retain the low cytotoxicity of DsRed-Express2. In addition, we show that these new FPs are useful as second or third colors for flow cytometry and fluorescence microscopy. Conclusion E2-Orange and E2-Red/Green will facilitate the production of healthy, stably fluorescent cell lines and transgenic organisms for multi-color labeling studies.

  6. 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.

  7. Circulating red cell-derived microparticles in human malaria.

    Science.gov (United States)

    Nantakomol, Duangdao; Dondorp, Arjen M; Krudsood, Srivicha; Udomsangpetch, Rachanee; Pattanapanyasat, Kovit; Combes, Valery; Grau, Georges E; White, Nicholas J; Viriyavejakul, Parnpen; Day, Nicholas P J; Chotivanich, Kesinee

    2011-03-01

    In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell-derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/μL [range, 13-4,342 RMPs/μL]), Plasmodium vivax (n = 5; median, 409 RMPs/μL [range, 281-503/μL]), and Plasmodium malariae (n = 2; median, 163 RMPs/μL [range, 127-200 RMPs/μL]) compared with those in healthy subjects (n = 11; median, 8 RMPs/μL [range, 3-166 RMPs/μL]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced >10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs.

  8. Red Cell Alloantibodies in Multiple Transfused Thalassaemia Patients.

    Science.gov (United States)

    Chaudhari, C N

    2011-01-01

    Thalassaemia major patients require lifelong transfusion support due to which they are prone for alloimmunization to foreign RBCs. Alloimmunization can be prevented by extended phenotype match blood transfusion. The study was conducted to know the extent of problem of alloimmunization and to find important red cell antibodies in thalassaemia patients. A cross-sectional study was conducted. A total of 32 thalassaemia patients were enrolled. The specimen was subjected to red cell alloantibody and autoantibody by column gel agglutination technique. R 1 (w) R 1 , R 2 R 2 , rr (papaine and non papain) and 11 cell panel reagent cells were used in screening and identification of alloantibodies respectively. Six (18.8 %) subjects were alloimmunized. All alloimmunized subjects were recipient of more than 20 units of transfusion. Total seven clinically significant alloantibodies were identified. Anti E and anti c were commonest antibodies in four (12.5%) patients. Red cell alloimmunization is an important risk in thalassaemia patient. 71.4% of alloantibodies were anti E and anti c type. Extended phenotype match blood transfusion for Rh-c and Rh-E antigens or level 2 antigen matching stringency needs to be explored in preventing alloimmunization in thalassaemia patients.

  9. Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells.

    Science.gov (United States)

    Kemp, Kevin; Dey, Rimi; Cook, Amelia; Scolding, Neil; Wilkins, Alastair

    2017-08-01

    Friedreich's ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich's ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich's ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich's ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich's ataxia.

  10. 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...

  11. Red Blood Cell Antibody Screen: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... medlineplus.gov/labtests/redbloodcellantibodyscreen.html Red Blood Cell Antibody Screen To use the sharing features on this page, please enable JavaScript. What is an RBC Antibody Screen? An RBC (red blood cell) antibody screen ...

  12. Red blood cell distribution width: biomarker for red cell dysfunction and critical illness outcome?

    Science.gov (United States)

    Said, Ahmed S.; Spinella, Philip C.; Hartman, Mary E.; Steffen, Katherine M.; Jackups, Ronald; Holubkov, Richard; Wallendorf, Mike; Doctor, Allan

    2016-01-01

    Objective Red blood cell distribution width (RDW) is reported to be an independent predictor of outcome in adults with a variety of conditions. We sought to determine if RDW is associated with morbidity or mortality in critically ill children. Design Retrospective observational study. Setting Tertiary pediatric intensive care unit. Patients All admissions to Saint Louis Children’s Hospital Pediatric Intensive Care Unit between 1/1/2005 and 12/31/2012. Interventions We collected demographics, laboratory values, hospitalization characteristics and outcomes. We calculated the relative change in RDW (R-RDW) from admission (A-RDW) to the highest RDW during the first 7 days of hospitalization. Our primary outcome was ICU mortality or use of ECMO as a composite. Secondary outcomes were ICU- and ventilator-free days. Measurements and main results We identified 3,913 eligible subjects with an estimated mortality (by PIM2) of 2.94±9.25% and an actual ICU mortality of 2.91%. For the study cohort, A-RDW was 14.12±1.89% and R-RDW was +2.63±6.23%. On univariate analysis, both A-RDW and R-RDW correlated with mortality or use of ECMO (OR=1.19 [95% CI: 1.12–1.27] and OR=1.06 [95% CI: 1.04–1.08], respectively, p<0.001). After adjusting for confounding variables, including severity of illness, both A-RDW (OR=1.13, 95% CI 1.03–1.24) and R-RDW (OR=1.04, 95% CI 1.01–1.07) remained independently associated with ICU mortality or use of ECMO. A-RDW and R-RDW both weakly correlated with fewer ICU-free (r2=0.038) and ventilator-free days, (r2=0.05), (p<0.001). Conclusions Independent of illness severity in critically ill children, A-RDW is associated with ICU mortality and morbidity. These data suggest that RDW may be a biomarker for RBC injury that is of sufficient magnitude to influence critical illness outcome, possibly via oxygen delivery impairment. PMID:27832023

  13. Мodification of Mechanical Limbal Stem Cell Deficiency Model

    Directory of Open Access Journals (Sweden)

    A. V. Bezushko

    2018-01-01

    Full Text Available Introduction. Ocular surface diseases related with limbal epithelial stem cells dysfunction were united in term “limbal stem cell  deficiency” (LSCD. For experimental study of the regenerative processes and evaluation of the success of new LSCD treatingmethods LSCD model is required. Various LSCD models were proposed in the experiment to study: mechanical, thermal, chemical,medicamental. The main lack of these models were the relative high cost and complexity of execution. The mechanical model allows forthe guaranteed removal of tissues containing LESCs, and therefore seems to be the most acceptable. We offered a modification of themechanical LSCD model in rabbits. Purpose to create a standardized modification of the mechanical limbal stem cell deficiency modelin the experiment. Material and methods. The experimental study was performed in 10 mature Chinchilla rabbits (20 eyes with anaverage weight 2.5–3.5 kg. With the local anesthesia, after a 40-second application of the filter paper impregnated with 20% ethanol,the corneal epithelium was removed. With microsurgical diamond blade we metered limb portion of 4 mm width, 0.2 mm deep, andit was removed along the 360° rim. Results. On the 30th day we discovered corneal opacity and neovascularization with conjunctivalpannus extending to the optical zone of the cornea. Histological examination revealed tissue edema, inflammatory infiltration, andnewly formed vessels. In some places, thinning of epithelium to one row of flattened cells was observed. The Bowman membrane wasdeformed and practically not detected. Histological examination and impression cytology confirmed the presence of goblet cells in thecorneal epithelium. Conclusions. Our modification of the mechanical limbal stem cell deficiency model is devoid of the main lacks ofprevious models, such as the high cost and complexity of execution, provides intraoperative limbal tissue resection depth control andexcludes the possibility of the

  14. 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

  15. Red blood cell-deformability measurement: review of techniques.

    Science.gov (United States)

    Musielak, M

    2009-01-01

    Cell-deformability characterization involves general measurement of highly complex relationships between cell biology and physical forces to which the cell is subjected. The review takes account of the modern technical solutions simulating the action of the force applied to the red blood cell in macro- and microcirculation. Diffraction ektacytometers and rheoscopes measure the mean deformability value for the total red blood cell population investigated and the deformation distribution index of individual cells, respectively. Deformation assays of a whole single cell are possible by means of optical tweezers. The single cell-measuring setups for micropipette aspiration and atomic force microscopy allow conducting a selective investigation of deformation parameters (e.g., cytoplasm viscosity, viscoelastic membrane properties). The distinction between instrument sensitivity to various RBC-rheological features as well as the influence of temperature on measurement are discussed. The reports quoted confront fascinating possibilities of the techniques with their medical applications since the RBC-deformability has the key position in the etiology of a wide range of conditions.

  16. Mismatch repair deficient hematopoietic stem cells are preleukemic stem cells.

    Directory of Open Access Journals (Sweden)

    Yulan Qing

    Full Text Available Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs, creating a preleukemic stem cell (PLSC. Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC. Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM, but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus. We studied PLSC linked to thymic lymphomas. In this study, we use MSH2-/- mice as a model to investigate the existence of PLSC and the evolution of PLSC to LIC. Following BM transplantation, we found that MSH2-/- BM cells from young mice are able to fully reconstitute multiple hematopoietic lineages of lethally irradiated wild-type recipients. However, all recipients developed thymic lymphomas within three and four months post transplantation. Transplantation of different fractions of BM cells or thymocytes from young health MSH2-/- mice showed that an HSC enriched fraction always reconstituted hematopoiesis followed by lymphoma development. In addition, lymphomas did not occur in thymectomized recipients of MSH2-/- BM. These results suggest that HSCs with DNA repair defects such as MSH2-/- are PLSCs because they retain hematopoietic function, but also carry an obligate lymphomagenic potential within their T-cell progeny that is dependent on the thymic microenvironment.

  17. Optimising methods of red cell sedimentation from cord blood to maximise nucleated cell recovery prior to cryopreservation.

    Science.gov (United States)

    Madkaikar, M; Gupta, M; Ghosh, K; Swaminathan, S; Sonawane, L; Mohanty, D

    2007-01-01

    Human cord blood is now an established source of stem cells for haematopoietic reconstitution. Red blood cell (RBC) depletion is required to reduce the cord blood unit volume for commercial banking. Red cell sedimentation using hydroxy ethyl starch (HES) is a standard procedure in most cord blood banks. However, while standardising the procedure for cord blood banking, a significant loss of nucleated cells (NC) may be encountered during standard HES sedimentation protocols. This study compares four procedures for cord blood processing to obtain optimal yield of nucleated cells. Gelatin, dextran, 6% HES and 6% HES with an equal volume of phosphate-buffered saline (PBS) were compared for RBC depletion and NC recovery. Dilution of the cord blood unit with an equal volume of PBS prior to sedimentation with HES resulted in maximum NC recovery (99% [99.5 +/- 1.3%]). Although standard procedures using 6% HES are well established in Western countries, they may not be applicable in India, as a variety of factors that can affect RBC sedimentation (e.g., iron deficiency, hypoalbuminaemia, thalassaemia trait, etc.) may reduce RBC sedimentation and thus reduce NC recovery. While diluting cord blood with an equal volume of PBS is a simple method to improve the NC recovery, it does involve an additional processing step.

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

    NARCIS (Netherlands)

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

    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

  19. Red blood cell and platelet genotyping: from current practice to future high-throughput donor typing

    NARCIS (Netherlands)

    de Haas, M.; van der Schoot, C. E.; Beiboer, S. H. W.; Feskens, M.; Cheroutre, G.; Maaskant-van Wijkb, P. A.

    2006-01-01

    The molecular basis of almost all red cell and platelet blood group antigens is known. This enables the prediction of red cell or platelet phenotypes based upon the genotypes. In many laboratories, blood group genotyping assays are routinely used in cases where patient red cells cannot be used for

  20. Effects of ethanol on red blood cell rheological behavior.

    Science.gov (United States)

    Rabai, M; Detterich, J A; Wenby, R B; Toth, K; Meiselman, H J

    2014-01-01

    Consumption of red wine is associated with a decreased risk of several cardiovascular diseases (e.g., coronary artery disease, stroke), but unfortunately literature reports regarding ethanol's effects on hemorheological parameters are not concordant. In the present study, red blood cell (RBC) deformability was tested via laser ektacytometry (LORCA, 0.3-30 Pa) using two approaches: 1) addition of ethanol to whole blood at 0.25%-2% followed by incubation and testing in ethanol-free LORCA medium; 2) addition of ethanol to the LORCA medium at 0.25%-6% then testing untreated native RBC in these media. The effects of ethanol on deformability for oxidatively stressed RBC were investigated as were changes of RBC aggregation (Myrenne Aggregometer) for cells in autologous plasma or 3% 70 kDa dextran. Significant dose-related increases of RBC deformability were observed at 0.25% (p health benefits of moderate wine consumption require further investigation.

  1. Pure Red Cell Aplasia Associated with Good Syndrome

    Directory of Open Access Journals (Sweden)

    Masayuki Okui

    2017-04-01

    Full Text Available Pure red cell aplasia (PRCA and hypogammaglobulinemia are paraneoplastic syndromes that are rarer than myasthenia gravis in patients with thymoma. Good syndrome coexisting with PRCA is an extremely rare pathology. We report the case of a 50-year-old man with thymoma and PRCA associated with Good syndrome who achieved complete PRCA remission after thymectomy and postoperative immunosuppressive therapy, and provide a review of the pertinent literature.

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

    OpenAIRE

    B. T. Dzumabaeva; L. S. Birjukova; L. B. Kaplanskaya; D. P. Maksimov

    2011-01-01

    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...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Complications Undiagnosed or untreated iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough hemoglobin-carrying red blood cells, your heart has to work harder to move oxygen-rich blood through your ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  5. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, van den G.J.; de Goeij, J.J.M.; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendriks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (<1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  6. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, G.J. van den; Goeij, J.J.M. de; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendruiks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  7. Zinc and antioxidant vitamin deficiency in patients with severe sickle cell anemia

    International Nuclear Information System (INIS)

    Hasanato, R.M. W.

    2006-01-01

    Patients with severe sickle cell anemia (SCA) have a higher potential for oxidative damage due to chronic redox imbalance in red blood cells that often leads to hemolysis, endothelial injury and recurrent vaso-occlusive episodes. This study evaluated the plasma levels of Vitamin A, C and E as indicators of antioxidants status. In addition, serum levels of zinc and copper were also estimated. Twenty-five adult patients with severe sickle cell anemia (12 males and 13 females aged 29.72+-12.94 years) and 25 matched controls were studied. Plasma levels of vitamin A, C and E were measured by HPLC technique. Serum zinc and copper levels were measured by atomic absorption spectrometry. There was significant decrease in plasma levels of vitamins A, C and E and in serum levels of zinc in patients with SCA as compared with controls (P<0.0001). Serum copper levels were significantly elevated compared with controls (P<0.0001). These findings emphasized the significant deficiencies of the antioxidant vitamins A, C and E and the trace element zinc along with the significant elevation of serum copper in patients with severe sickle cell disease. Further studies are needed to find out whether supplementation of antioxidant vitamins and zinc may ameliorate some sickle cell disease complications. (author)

  8. 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.

  9. Dysregulation of Aldosterone Secretion in Mast Cell-Deficient Mice.

    Science.gov (United States)

    Boyer, Hadrien-Gaël; Wils, Julien; Renouf, Sylvie; Arabo, Arnaud; Duparc, Céline; Boutelet, Isabelle; Lefebvre, Hervé; Louiset, Estelle

    2017-12-01

    Resident adrenal mast cells have been shown to activate aldosterone secretion in rat and man. Especially, mast cell proliferation has been observed in adrenal tissues from patients with aldosterone-producing adrenocortical adenoma. In the present study, we show that the activity of adrenal mast cells is stimulated by low-sodium diet and correlates with aldosterone synthesis in C57BL/6 and BALB/c mice. We have also investigated the regulation of aldosterone secretion in mast cell-deficient C57BL/6 Kit W-sh/W-sh mice in comparison with wild-type C57BL/6 mice. Kit W-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in wild-type animals. Conversely, low-sodium diet unexpectedly induced an exaggerated aldosterone response, which seemed to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was associated with an increase in systolic blood pressure and marked hypokalemia, which favored polyuria. Adrenal renin and angiotensin type 1 receptor overexpression may represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Finally, C57BL/6 Kit W-sh/W-sh mice represent an unexpected animal model of primary aldosteronism, which has the particularity to be triggered by sodium restriction. © 2017 American Heart Association, Inc.

  10. 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.

  11. Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery

    Science.gov (United States)

    Carpenter, Cody Westcott

    Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

  12. The absolute counting of red cell-derived microparticles with red cell bead by flow rate based assay.

    Science.gov (United States)

    Nantakomol, Duangdao; Imwong, Malika; Soontarawirat, Ingfar; Kotjanya, Duangporn; Khakhai, Chulalak; Ohashi, Jun; Nuchnoi, Pornlada

    2009-05-01

    Activation of red blood cell is associated with the formation of red cell-derived microparticles (RMPs). Analysis of circulating RMPs is becoming more refined and clinically useful. A quantitative Trucount tube method is the conventional method uses for quantitating RMPs. In this study, we validated a quantitative method called "flow rate based assay using red cell bead (FCB)" to measure circulating RMPs in the peripheral blood of healthy subjects. Citrated blood samples collected from 30 cases of healthy subjects were determined the RMPs count by using double labeling of annexin V-FITC and anti-glycophorin A-PE. The absolute RMPs numbers were measured by FCB, and the results were compared with the Trucount or with flow rate based calibration (FR). Statistical correlation and agreement were analyzed using linear regression and Bland-Altman analysis. There was no significant difference in the absolute number of RMPs quantitated by FCB when compared with those two reference methods including the Trucount tube and FR method. The absolute RMPs count obtained from FCB method was highly correlated with those obtained from Trucount tube (r(2) = 0.98, mean bias 4 cell/microl, limit of agreement [LOA] -20.3 to 28.3 cell/microl), and FR method (r(2) = 1, mean bias 10.3 cell/microl, and LOA -5.5 to 26.2 cell/microl). This study demonstrates that FCB is suitable and more affordable for RMPs quantitation in the clinical samples. This method is a low cost and interchangeable to latex bead-based method for generating the absolute counts in the resource-limited areas. (c) 2008 Clinical Cytometry Society.

  13. Red Cell Indexes Made Easy Using an Interactive Animation: Do Students and Their Scores Concur?

    Science.gov (United States)

    Kachroo, Upasana; Vinod, Elizabeth; Balasubramanian, Sivakumar; W., Jesi; Prince, Neetu

    2018-01-01

    A good understanding of red cell indexes can aid medical students in a considerable manner, serving as a basis to unravel both concepts in red cell physiology and abnormalities associated with the same. In this study, we tried to assess whether an interactive animation was helpful in improving student comprehension and understanding of red cell…

  14. Congenital CMV with LAD type 1 and NK cell deficiency.

    Science.gov (United States)

    Rai, Narendra; Thakur, Neha

    2013-08-01

    We report a rare case of congenital cytomegalovirus (CMV) in a patient who was subsequently diagnosed as leukocyte adhesion defect type 1 with natural killer cell deficiency. The clinical course was complicated by severe CMV pneumonitis during the newborn period. Thereafter the infant suffered from recurrent skin infections without pus formation, otitis media, and bronchopneumonia since 3 months of age. The patient had congenital CMV infection as urine and blood plasma was positive for CMV from day 12 onward. Neutrophil chemotaxis studies showed a decrease in directed chemotaxis. Neutrophils were dyspoetic and nonfunctional lacking HLA DR, CD11c, and CD18. Lymphocytes were polyclonal but lacked CD56, CD16, and surface membrane immunoglobulin.

  15. 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.

  16. Measuring osmosis and hemolysis of red blood cells.

    Science.gov (United States)

    Goodhead, Lauren K; MacMillan, Frances M

    2017-06-01

    Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the cell's interior. The selectively permeable nature of the cell membrane allows the movement of some solutes and prevents the movement of others. This has important consequences for cell volume and the integrity of the cell and, as a result, is of utmost clinical importance, for example in the administration of isotonic intravenous infusions. The concepts of osmolarity and tonicity are often confused by students as impermeant isosmotic solutes such as NaCl are also isotonic; however, isosmotic solutes such as urea are actually hypotonic due to the permeant nature of the membrane. By placing red blood cells in solutions of differing osmolarities and tonicities, this experiment demonstrates the effects of osmosis and the resultant changes in cell volume. Using hemoglobin standard solutions, where known concentrations of hemoglobin are produced, the proportion of hemolysis and the effect of this on resultant hematocrit can be estimated. No change in cell volume occurs in isotonic NaCl, and, by placing blood cells in hypotonic NaCl, incomplete hemolysis occurs. By changing the bathing solution to either distilled water or isosmotic urea, complete hemolysis occurs due to their hypotonic effects. With the use of animal blood in this practical, students gain useful experience in handling tissue fluids and calculating dilutions and can appreciate the science behind clinical scenarios. Copyright © 2017 the American Physiological Society.

  17. Red blood cell transfusion for people undergoing hip fracture surgery.

    Science.gov (United States)

    Brunskill, Susan J; Millette, Sarah L; Shokoohi, Ali; Pulford, E C; Doree, Carolyn; Murphy, Michael F; Stanworth, Simon

    2015-04-21

    The incidence of hip fracture is increasing and it is more common with increasing age. Surgery is used for almost all hip fractures. Blood loss occurs as a consequence of both the fracture and the surgery and thus red blood cell transfusion is frequently used. However, red blood cell transfusion is not without risks. Therefore, it is important to identify the evidence for the effective and safe use of red blood cell transfusion in people with hip fracture. To assess the effects (benefits and harms) of red blood cell transfusion in people undergoing surgery for hip fracture. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (31 October 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 10), MEDLINE (January 1946 to 20 November 2014), EMBASE (January 1974 to 20 November 2014), CINAHL (January 1982 to 20 November 2014), British Nursing Index Database (January 1992 to 20 November 2014), the Systematic Review Initiative's Transfusion Evidence Library, PubMed for e-publications, various other databases and ongoing trial registers. Randomised controlled trials comparing red blood cell transfusion versus no transfusion or an alternative to transfusion, different transfusion protocols or different transfusion thresholds in people undergoing surgery for hip fracture. Three review authors independently assessed each study's risk of bias and extracted data using a study-specific form. We pooled data where there was homogeneity in the trial comparisons and the timing of outcome measurement. We used GRADE criteria to assess the quality (low, moderate or high) of the evidence for each outcome. We included six trials (2722 participants): all compared two thresholds for red blood cell transfusion: a 'liberal' strategy to maintain a haemoglobin concentration of usually 10 g/dL versus a more 'restrictive' strategy based on symptoms of anaemia or a lower haemoglobin concentration, usually 8 g/dL. The exact

  18. 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

    better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

  19. Anthocyanin-Rich Extract from Red Chinese Cabbage Alleviates Vascular Inflammation in Endothelial Cells and Apo E−/− Mice

    Directory of Open Access Journals (Sweden)

    Hee Kyoung Joo

    2018-03-01

    Full Text Available Anthocyanins, the most prevalent flavonoids in red/purple fruits and vegetables, are known to improve immune responses and reduce chronic disease risks. In this study, the anti-inflammatory activities of an anthocyanin-rich extract from red Chinese cabbage (ArCC were shown based on its inhibitory effects in cultured endothelial cells and hyperlipidemic apolipoprotein E-deficient mice. ArCC treatment suppressed monocyte adhesion to tumor necrosis factor-α-stimulated endothelial cells. This was validated by ArCC’s ability to downregulate the expression and transcription of endothelial adhesion molecules, determined by immunoblot and luciferase promoter assays, respectively. The regulation of adhesion molecules was accompanied by transcriptional inhibition of nuclear factor-κB, which restricted cytoplasmic localization as shown by immunocytochemistry. Administration of ArCC (150 or 300 mg/kg/day inhibited aortic inflammation in hyperlipidemic apolipoprotein E-deficient mice, as shown by in vivo imaging. Immunohistochemistry and plasma analysis showed that the aortas from these mice exhibited markedly lower leukocyte infiltration, reduced plaque formation, and lower concentrations of blood inflammatory cytokines than those observed in the control mice. The results suggest that the consumption of anthocyanin-rich red Chinese cabbage is closely correlated with lowering the risk of vascular inflammatory diseases.

  20. Automatic analysis of microscopic images of red blood cell aggregates

    Science.gov (United States)

    Menichini, Pablo A.; Larese, Mónica G.; Riquelme, Bibiana D.

    2015-06-01

    Red blood cell aggregation is one of the most important factors in blood viscosity at stasis or at very low rates of flow. The basic structure of aggregates is a linear array of cell commonly termed as rouleaux. Enhanced or abnormal aggregation is seen in clinical conditions, such as diabetes and hypertension, producing alterations in the microcirculation, some of which can be analyzed through the characterization of aggregated cells. Frequently, image processing and analysis for the characterization of RBC aggregation were done manually or semi-automatically using interactive tools. We propose a system that processes images of RBC aggregation and automatically obtains the characterization and quantification of the different types of RBC aggregates. Present technique could be interesting to perform the adaptation as a routine used in hemorheological and Clinical Biochemistry Laboratories because this automatic method is rapid, efficient and economical, and at the same time independent of the user performing the analysis (repeatability of the analysis).

  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 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. 

  3. 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 salva...

  4. [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.

  5. Volume-dependent K+ transport in rabbit red blood cells comparison with oxygenated human SS cells

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rohil, N.; Jennings, M.L.

    1989-07-01

    In this study the volume-dependent or N-ethylmaleimide (NEM)-stimulated, ouabain-insensitive K+ influx and efflux were measured with the tracer 86Rb+ in rabbit red blood cells. The purpose of the work was to examine the rabbit as a potential model for cell volume regulation in human SS red blood cells and also to investigate the relationship between the NEM-reactive sulfhydryl group(s) and the signal by which cell swelling activates the transport. Ouabain-resistant K+ efflux and influx increase nearly threefold in cells swollen hypotonically by 15%. Pretreatment with 2 mM NEM stimulates efflux 5-fold and influx 10-fold (each measured in an isotonic medium). The ouabain-resistant K+ efflux was dependent on the major anion in the medium. The anion dependence of K+ efflux in swollen or NEM-stimulated cells was as follows: Br- greater than Cl- much greater than NO3- = acetate. The magnitudes of both the swelling- and the NEM-stimulated fluxes are much higher in young cells (density separated but excluding reticulocytes) than in older cells. Swelling- or NEM-stimulated K+ efflux in rabbit red blood cells was inhibited 50% by 1 mM furosemide, and the inhibitory potency of furosemide was enhanced by extracellular K+, as is known to be true for human AA and low-K+ sheep red blood cells. The swelling-stimulated flux in both rabbit and human SS cells has a pH optimum at approximately 7.4. We conclude that rabbit red blood cells are a good model for swelling-stimulated K+ transport in human SS cells.

  6. Assessment of red cell sodium transport in essential hypertension

    International Nuclear Information System (INIS)

    Mahoney, J.R.; Etkin, N.L.; McSwigan, J.D.; Eaton, J.W.

    1982-01-01

    Abnormal erythrocyte Na+ transport has been reported in patients with essential hypertension and some first-degree relatives. The two major techniques now employed for estimating Na+ transport--Na+/Li+ countertransport and Na+/K+ cotransport--are rather intricate and time consuming. Furthermore, the precise nature of the transport processes being measured is not clear. We have developed a simpler, more direct technique based on measurement of 22Na+ accumulation by erythrocytes. 22Na+ uptake by red cells from patients with essential hypertension averages twice normal. Indeed, of 21 patients with essential hypertension, only 2 patients had values within the upper end of the normal range. In 12 patients with secondary hypertension and no family history of essential hypertension, erythrocyte 22Na+ accumulation was within normal limits. Control experiments indicate that our technique for estimating red cell 22Na+ uptake is highly reproducible and shows little day-to-day variation. This procedure for the assessment of erythrocyte Na+ transport should be useful in differential diagnosis and the presymptomatic identification of individuals genetically prone to essential hypertension

  7. Utilization of red blood cell transfusion in an obstetric setting.

    Science.gov (United States)

    Kamani, A A; McMorland, G H; Wadsworth, L D

    1988-11-01

    The transfusion experience for a 1-year period (September 1985 to August 1986) at a tertiary referral obstetric hospital was reviewed retrospectively. During the review period 7731 mothers were delivered and 6003 patients (83%) underwent type-and-screen procedures. A total of 1057 units of red blood cells were crossmatched, and 362 of these 1057 units were transfused to 100 parturient women so that the overall crossmatch/transfusion ratio was 2.9:1. Five percent of transfused patients received 1 unit; 52% of patients received 2 units, 19% received 3 units and 24% received greater than or equal to 4 units of packed red blood cells. Major indications for transfusion were uterine atony, 27%; retained placenta, 17%; trauma, 17%, placenta previa, 7%; and abruptio placentae, 5%. In 12% of patients transfusions were done because of anemia. This study shows the value of audit and confirms that the type-and-screen procedure is an effective way of reducing the crossmatch/transfusion ratio without compromising patient care, even in high-risk patients.

  8. Attenuation of Red Blood Cell Storage Lesions with Vitamin C

    Directory of Open Access Journals (Sweden)

    Kimberly Sanford

    2017-07-01

    Full Text Available Stored red blood cells (RBCs undergo oxidative stress that induces deleterious metabolic, structural, biochemical, and molecular changes collectively referred to as “storage lesions”. We hypothesized that vitamin C (VitC, reduced or oxidized would reduce red cell storage lesions, thus prolonging their storage duration. Whole-blood-derived, leuko-reduced, SAGM (saline-adenine-glucose-mannitol-preserved RBC concentrates were equally divided into four pediatric storage bags and the following additions made: (1 saline (saline; (2 0.3 mmol/L reduced VitC (Lo VitC; (3 3 mmol/L reduced VitC (Hi VitC; or (4 0.3 mmol/L oxidized VitC (dehydroascorbic acid, DHA as final concentrations. Biochemical and rheological parameters were serially assessed at baseline (prior to supplementation and Days 7, 21, 42, and 56 for RBC VitC concentration, pH, osmotic fragility by mechanical fragility index, and percent hemolysis, LDH release, glutathione depletion, RBC membrane integrity by scanning electron microscopy, and Western blot for β-spectrin. VitC exposure (reduced and oxidized significantly increased RBC antioxidant status with varying dynamics and produced trends in reduction in osmotic fragility and increases in membrane integrity. Conclusion: VitC partially protects RBC from oxidative changes during storage. Combining VitC with other antioxidants has the potential to improve long-term storage of RBC.

  9. 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

    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

  10. 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. 864.8185 Section 864.8185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8185...

  11. Erythrokinetics, ferrokinetics and red cell survival in sickle cell anaemia under subtropical climatic conditions

    International Nuclear Information System (INIS)

    Cardenas, R.

    1975-01-01

    Ferrokinetic parameters were evaluated with 59 Fe and red-cell survival with 51 Cr by classical techniques in a total of 17 patients with sickle-cell disease. The mean plasma 59 Fe half-disappearance time in these patients was 29.5 min as compared with a normal value of 92 min, and the t1/2 51 Cr 8.0 days as compared with a normal value of 26.0 days. The mean red-cell iron turnover rate was elevated to 9 times normal. The increased destruction of red cells appeared to take place predominantly, though not entirely, in the spleen. Eight of the 17 patients studied were identified as having intercurrent complications, but these did not significantly affect the results of the investigations. A group of 5 boys in whom the red-cell iron turnover rate was elevated to a lesser degree than in the other patients were subjected to more detailed studies of plasma 59 Fe clearance with particular reference to ineffective erythropoiesis. In these patients, the plasma 59 Fe clearance curves showed precocious humps characteristic of ineffective erythropoiesis. Detailed analysis of the results indicated ineffective erythropoiesis corresponding to 3.6, 16.0, 22.6, 32.0 and 50.0 % of the iron initially taken up by the bone marrow. It is concluded that while the anaemia in most patients with sickle-cell disease is mainly due to shortened survival of the circulating red cells, with increased destruction of red cells in the spleen, ineffective erythropoiesis may none the less be an important factor determining the actual degree of this anaemia

  12. Anisotropic light scattering of individual sickle red blood cells.

    Science.gov (United States)

    Kim, Youngchan; Higgins, John M; Dasari, Ramachandra R; Suresh, Subra; Park, YongKeun

    2012-04-01

    We present the anisotropic light scattering of individual red blood cells (RBCs) from a patient with sickle cell disease (SCD). To measure light scattering spectra along two independent axes of elongated-shaped sickle RBCs with arbitrary orientation, we introduce the anisotropic Fourier transform light scattering (aFTLS) technique and measured both the static and dynamic anisotropic light scattering. We observed strong anisotropy in light scattering patterns of elongated-shaped sickle RBCs along its major axes using static aFTLS. Dynamic aFTLS analysis reveals the significantly altered biophysical properties in individual sickle RBCs. These results provide evidence that effective viscosity and elasticity of sickle RBCs are significantly different from those of the healthy RBCs.

  13. Transfusion of Packed Red Blood Cells--The Indications Have Changed.

    Science.gov (United States)

    Cook, Alan; Miller, Nate

    2015-12-01

    Whole blood/packed red blood cells (pRBC) units transfused in the U.S. totaled 13,785,000 in 2011. A single institution in South Dakota transfused 6,485 units of pRBC in 2013. Current thresholds for transfusion have changed and each transfusion has the risk of causing an adverse reaction; thus, it is important to ensure pRBCs are administered appropriately. Due to these changes and the potential risks associated with transfusion, we reviewed the literature regarding appropriate indications for transfusion of pRBC. Our review specifically focused on four disease entities: iron-deficiency anemia, acute upper gastrointestinal (GI) bleeding, acute coronary syndromes, and chronic ischemic heart disease. Based on our findings, we recommend utilizing an overall conservative approach to the transfusion of pRBC. In patients with iron-deficiency anemia, first try alternative methods to improve hemoglobin levels; in those with acute GI bleeding, transfuse for hemoglobin less than 7 g/dL; in patients with acute coronary syndromes, let symptoms/signs be your guide; and in patients with ischemic heart disease, transfuse for hemoglobin levels less than 8 g/dL or if they are symptomatic. Most importantly, be cautious to not fixate on numbers alone; always incorporate patients' symptoms and co-morbidities when considering whether to transfuse pRBCs.

  14. [Establishment and identification of mouse lymphoma cell line EL4 expressing red fluorescent protein].

    Science.gov (United States)

    Li, Yan-Jie; Cao, Jiang; Chen, Chong; Wang, Dong-Yang; Zeng, Ling-Yu; Pan, Xiu-Ying; Xu, Kai-Lin

    2010-02-01

    This study was purposed to construct a lentiviral vector encoding red fluorescent protein (DsRed) and transfect DsRed into EL4 cells for establishing mouse leukemia/lymphoma model expressing DsRed. The bicistronic SIN lentiviral transfer plasmid containing the genes encoding neo and internal ribosomal entry site-red fluorescent protein (IRES-DsRed) was constructed. Human embryonic kidney 293FT cells were co-transfected with the three plasmids by liposome method. The viral particles were collected and used to transfect EL4 cells, then the cells were selected by G418. The results showed that the plasmid pXZ208-neo-IRES-DsRed was constructed successfully, and the viral titer reached to 10(6) U/ml. EL4 cells were transfected by the viral solution efficiently. The transfected EL4 cells expressing DsRed survived in the final concentration 600 microg/ml of G418. The expression of DsRed in the transfected EL4 cells was demonstrated by fluorescence microscopy and flow cytometry. In conclusion, the EL4/DsRed cell line was established successfully.

  15. 3D morphometry of red blood cells by digital holography.

    Science.gov (United States)

    Memmolo, Pasquale; Miccio, Lisa; Merola, Francesco; Gennari, Oriella; Netti, Paolo Antonio; Ferraro, Pietro

    2014-12-01

    Three dimensional (3D) morphometric analysis of flowing and not-adherent cells is an important aspect for diagnostic purposes. However, diagnostics tools need to be quantitative, label-free and, as much as possible, accurate. Recently, a simple holographic approach, based on shape from silhouette algorithm, has been demonstrated for accurate calculation of cells biovolume and displaying their 3D shapes. Such approach has been adopted in combination with holographic optical tweezers and successfully applied to cells with convex shape. Nevertheless, unfortunately, the method fails in case of specimen with concave surfaces. Here, we propose an effective approach to achieve correct 3D shape measurement that can be extended in case of cells having concave surfaces, thus overcoming the limit of the previous technique. We prove the new procedure for healthy red blood cells (RBCs) (i.e., discocytes) having a concave surface in their central region. Comparative analysis of experimental results with a theoretical 3D geometrical model of RBC is discussed in order to evaluate accuracy of the proposed approach. Finally, we show that the method can be also useful to classify, in terms of morphology, different varieties of RBCs. © 2014 International Society for Advancement of Cytometry.

  16. Survival of transfused red blood cells: In vivo compatibility testing with chromium-51

    International Nuclear Information System (INIS)

    Dharkar, D.D.; Pineda, A.A.

    1983-01-01

    The /sup 51/Cr red cell survival test and specific test for measurement of the disappearance rate of labeled red cells. This procedure can be used for the assessment of red cell compatibility testing in vivo. The authors recommend that more routine transfusions as well as ''difficult'' transfusions be monitored by /sup 51/Cr in vivo compatibility testing before the actual transfusions, so that more consistent and reliable survival values are achieved

  17. 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.

  18. 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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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. (paper)

  19. Characterization of immortalized MARCO and SR-AI/II-deficient murine alveolar macrophage cell lines

    Directory of Open Access Journals (Sweden)

    Imrich Amy

    2008-05-01

    Full Text Available Abstract Background Alveolar macrophages (AM avidly bind and ingest unopsonized inhaled particles and bacteria through class A scavenger receptors (SRAs MARCO and SR-AI/II. Studies to characterize the function of these SRAs have used AMs from MARCO or SR-AI/II null mice, but this approach is limited by the relatively low yield of AMs. Moreover, studies using both MARCO and SR-AI/II-deficient (MS-/- mice have not been reported yet. Hence, we sought to develop continuous cell lines from primary alveolar macrophages from MS-/- mice. Results We used in vitro infection of the primary AMs with the J2 retrovirus carrying the v-raf and v-myc oncogenes. Following initial isolation in media supplemented with murine macrophage colony-stimulating factor (M-CSF, we subcloned three AM cell lines, designated ZK-1, ZK-2 and ZK-6. These cell lines grow well in RPMI-1640-10% FBS in the absence of M-CSF. These adherent but trypsin-sensitive cell lines have a doubling time of approximately 14 hours, exhibit typical macrophage morphology, and express macrophage-associated cell surface Mac-1 (CD11b and F4/80 antigens. The cell lines show robust Fc-receptor dependent phagocytosis of opsonized red blood cells. Similar to freshly isolated AMs from MS-/- mice, the cell lines exhibit decreased phagocytosis of unopsonized titanium dioxide (TiO2, fluorescent latex beads and bacteria (Staphylococcus aureus compared with the primary AMs from wild type (WT C57BL/6 mice. Conclusion Our results indicated that three contiguous murine alveolar macrophage cell lines with MS-/- (ZK1, ZK2 and ZK6 were established successfully. These cell lines demonstrated macrophage morphology and functional activity. Interestingly, similar to freshly isolated AMs from MS-/- mice, the cell lines have a reduced, but not absent, ability to bind and ingest particles, with an altered pattern of blockade by scavenger receptor inhibitors. These cell lines will facilitate in vitro studies to further define

  20. Hyperemic peripheral red marrow in a patient with sickle cell anemia demonstrated on Tc-99m labeled red blood cell venography

    International Nuclear Information System (INIS)

    Heiden, R.A.; Locko, R.C.; Stent, T.R.

    1991-01-01

    A 25-year-old gravid woman, homozygous for sickle cell anemia, with a history of recent deep venous thrombosis, was examined using Tc-99m labeled red blood cell venography for recurrent thrombosis. Although negative for thrombus, the study presented an unusual incidental finding: the patient's peripheral bone marrow was hyperemic in a distribution consistent with peripheral red bone marrow expansion. Such a pattern has not been documented before using this technique. This report supports other literature that has demonstrated hyperemia of peripheral red bone marrow in other hemolytic anemias. This finding may ultimately define an additional role of scintigraphy in assessing the pathophysiologic status of the sickle cell patient

  1. Hemoglobin, red blood cell count, hematocrit and derived parameters for diagnosing anemia in elderly males

    International Nuclear Information System (INIS)

    Khan, Z.; Nawaz, M.

    2013-01-01

    Anemia is one of the most common micronutrient deficiency in our community. Nutritional anaemias are caused when there is an inadequate body store of a specific nutrient needed for hemoglobin synthesis. The most common nutrient deficiency is of iron. Therefore, a cross-sectional survey was conducted on the healthy elderly male, aged >= 40 and 77 years (n=60) volunteers in order to assess their blood parameters, such as hemoglobin concentration (Hb), hematocrit (HCT), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) for the diagnosis of anemia. The demographic results showed mean values (50.10+-8.79) years for age, 66-68 +- 1.95 inches for height , 71.43 +- 6.43 kg body weight, 98.34+-0.48 degree F body temperature, 124 +- 8.67 systolic blood pressure, 82.17 +- 4.15 diastolic pressure while, The pulse rate was found to be 74.63 +- 7.02/minute. Similarly, mean values for lean body weight (LBW) found to be 49.9+-2.89, ideal body weight (IBW) 60.9 +- 4.49, body surface area (BSA) was 1.8 +- 0.1 m2 whereas, body mass index (BMI) showed mean value 24.9 +- 2.6 kg/m2. More so, overall mean Hb found to be 13.60 g/dl, RBC 4.6 mill/mm3, HCT/PCV 43%, MCV 92.95fl, MCH 29.42 pg and MCHC was found to be 31.73 g/dl. The normal range of Hb for men was 13-17 g/dl and 31.67% of the subjects participated in the study was considered to be anemic showing less Hb than normal range. The volunteers were suggested to improve the dietary habits and to take iron supplements in order to overcome the iron deficiency anemia. (author)

  2. Red Dot Basal Cell Carcinoma: An Unusual Variant of a Common Malignancy.

    Science.gov (United States)

    Loh, Tiffany Y; Cohen, Philip R

    2016-05-01

    Red dot basal cell carcinoma is a distinct but rare subtype of basal cell carcinoma (BCC). It presents as a red macule or papule; therefore, in most cases, it may easily be mistaken for a benign vascular lesion, such as a telangiectasia or angioma. A red dot BCC in an older woman is described. Clinical and histological differences between red dot BCCs and telangiectasias are described. A 72-year-old woman initially presented with a painless red macule on her nose. Biopsy of the lesion established the diagnosis of a red dot BCC. Pubmed was searched for the following terms: angioma, basal cell carcinoma, dermoscope, diascopy, red dot, non-melanoma skin cancer, telangiectasia, and vascular. The papers were reviewed for cases of red dot basal cell carcinoma. Clinical and histological characteristics of red dot basal cell carcinoma and telangiectasias were compared. Red dot BCC is an extremely rare variant of BCC that may be confused with benign vascular lesions. Although BCCs rarely metastasize and are associated with low mortality, they have the potential to become locally invasive and destructive if left untreated. Thus, a high index of suspicion for red dot BCC is necessary. J Drugs Dermatol. 2016;15(5):645-647.

  3. Raman spectroscopic studies of optically trapped red blood cells

    International Nuclear Information System (INIS)

    Dasgupta, R.; Gupta, P.K.

    2010-01-01

    Raman spectroscopic studies were performed on optically trapped red blood cells (RBCs) collected from healthy volunteers and patients suffering from malaria (Plasmodium vivax infection) using near infrared (785 nm) laser source. The results show significant alteration in the spectra averaged over ∼ 50 non-parasitized RBCs per sample. As compared to RBCs from healthy donors, in cells collected from malaria patients, a significant decrease in the intensity of the low spin (oxygenated-haemoglobin) marker Raman band at 1223 cm -1 (υ 13 or υ 42 ) along with a concomitant increase in the high spin (deoxygenated-haemoglobin) marker bands at 1210 cm -1 (υ 5 + υ 18 ) and 1546 cm -1 (υ 11 ) was observed. The changes primarily suggest a reduced haemoglobin-oxygen affinity for the non-parasitized red cells in malaria patients. The possible causes include up regulation of intra-erythrocytic 2,3-diphosphoglycerate and/or ineffective erythropoiesis resulted from the disease. During the above study we also observed that significant photo-damage may results to the intracellular haemoglobin (Hb) if higher laser power is used. For a laser power above ∼ 5 mW the observed increase in intensity of the Raman bands at 975 cm -1 (υ 46 ), 1244 cm -1 (υ 42 ) and 1366 cm -1 (υ 4 ) with increasing exposure time suggests photo-denaturation of Hb and the concomitant decrease in intensity of the Raman band at 1544 cm -1 (υ 11 ) suggests photo induced methaemoglobin formation. The photo damage of intracellular haemoglobin by the above processes was also observed to result in intracellular heme aggregation. (author)

  4. 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.

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

    KAUST Repository

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

    2013-01-01

    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.

  6. Hemoglobin redox reactions and red blood cell aging.

    Science.gov (United States)

    Rifkind, Joseph M; Nagababu, Enika

    2013-06-10

    The physiological mechanism(s) for recognition and removal of red blood cells (RBCs) from circulation after 120 days of its lifespan is not fully understood. Many of the processes thought to be associated with the removal of RBCs involve oxidative stress. We have focused on hemoglobin (Hb) redox reactions, which is the major source of RBC oxidative stress. The importance of Hb redox reactions have been shown to originate in large parts from the continuous slow autoxidation of Hb producing superoxide and its dramatic increase under hypoxic conditions. In addition, oxidative stress has been shown to be associated with redox reactions that originate from Hb reactions with nitrite and nitric oxide (NO) and the resultant formation of highly toxic peroxynitrite when NO reacts with superoxide released during Hb autoxidation. The interaction of Hb, particularly under hypoxic conditions with band 3 of the RBC membrane is critical for the generating the RBC membrane changes that trigger the removal of cells from circulation. These changes include exposure of antigenic sites, increased calcium leakage into the RBC, and the resultant leakage of potassium out of the RBC causing cell shrinkage and impaired deformability. The need to understand the oxidative damage to specific membrane proteins that result from redox reactions occurring when Hb is bound to the membrane. Proteomic studies that can pinpoint the specific proteins damaged under different conditions will help elucidate the cellular aging processes that result in cells being removed from circulation.

  7. Detection and quantification of subtle changes in red blood cell density using a cell phone.

    Science.gov (United States)

    Felton, Edward J; Velasquez, Anthony; Lu, Shulin; Murphy, Ryann O; ElKhal, Abdala; Mazor, Ofer; Gorelik, Pavel; Sharda, Anish; Ghiran, Ionita C

    2016-08-16

    Magnetic levitation has emerged as a technique that offers the ability to differentiate between cells with different densities. We have developed a magnetic levitation system for this purpose that distinguishes not only different cell types but also density differences in cells of the same type. This small-scale system suspends cells in a paramagnetic medium in a capillary placed between two rare earth magnets, and cells levitate to an equilibrium position determined solely by their density. Uniform reference beads of known density are used in conjunction with the cells as a means to quantify their levitation positions. In one implementation images of the levitating cells are acquired with a microscope, but here we also introduce a cell phone-based device that integrates the magnets, capillary, and a lens into a compact and portable unit that acquires images with the phone's camera. To demonstrate the effectiveness of magnetic levitation in cell density analysis we carried out levitation experiments using red blood cells with artificially altered densities, and also levitated those from donors. We observed that we can distinguish red blood cells of an anemic donor from those that are healthy. Since a plethora of disease states are characterized by changes in cell density magnetic cell levitation promises to be an effective tool in identifying and analyzing pathologic states. Furthermore, the low cost, portability, and ease of use of the cell phone-based system may potentially lead to its deployment in low-resource environments.

  8. Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.

    Science.gov (United States)

    Cheng, Chiung-Chi; Chao, Wei-Ting; Liao, Chen-Chun; Tseng, Yu-Hui; Lai, Yen-Chang Clark; Lai, Yih-Shyong; Hsu, Yung-Hsiang; Liu, Yi-Hsiang

    2018-01-02

    Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib. Hepatoma cell lines PLC/PRF/5 and HepG2 were used to examine the level of plectin expression and cell migration in comparison with Chang liver cell line. In addition, sensitivity of the 3 cell lines to sorafenib treatment was also measured. Expression of plectin was lower in PLC/PRF/5 and HepG2 hepatoma cells than that of Chang liver cells whereas HepG2 and PLC/PRF/5 cells exhibit higher rate of cell migration in trans-well migration assay. Immunohistofluorecent staining on E-cadherin revealed the highest rate of collective cell migration in HepG2 cells and the lowest was found in Chang liver cells. Likewise, HepG2 cell line was most sensitive to sorafenib treatment and Chang liver cells exhibited the least sensitivity. The drug sensitivity to sorafenib treatment showed inverse correlation with the expression of plectin. We suggest that plectin deficiency and increased E-cadherin in hepatoma cells were associated with higher rates of cell motility, collective cell migration as well as higher drug sensitivity to sorafenib treatment.

  9. 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.

  10. Studies on ADCC (antibody-dependent cell-mediated cytotoxicity) using sheep red blood cells as target cells, 2

    International Nuclear Information System (INIS)

    Ichikawa, Yukinobu; Takaya, Masatoshi; Arimori, Shigeru

    1979-01-01

    A non-specific cytotoxic mediator from effector cells (human peripheral blood leukocytes) was investigated in the ADCC (antibody-dependent cell-mediated cytotoxicity) system using antibody-coated sheep red blood cells (SRBC) as target cells. 51 Cr-labelled homologous (sheep) or heterologous (human) red blood cells were used as adjacent cells. Either crude lymphocyte fraction, phagocyte depleted fraction or granulocyte rich fraction separated from human peripheral leukocytes showed moderate cytotoxic effect on homologous adjacent cells, however no cytotoxic activity on heterologous adjacent cells was demonstrated in any leukocyte fraction. This suggests that the cytotoxic effects on homologous adjacent cells were resulted from the translocation of antibody molecules to adjacent cells from antibody-coated target cells. We concluded that the cytotoxic mechanism in this ADCC system was not mediated by non-specific soluble factors released from either human peripheral lymphocytes, monocytes or granulocytes. (author)

  11. 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

    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...

  12. 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...

  13. 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

  14. Mechanisms of Xenon Effect on Skin and Red Blood Cells

    DEFF Research Database (Denmark)

    Ponomarev, Alexander; Rodin, V.; Gurevich, Leonid

    2017-01-01

    The usage of Xenon (Xe) is known in anesthesia and biobanking areas. It is considered preservation effect of Xe is associated either with clathrate formation - solid gaseous structures or dissolution of Xe molecules in liquid phase without physical state modification (so-called hyperbarium) [1......]. This study is addressed to establish differences between hyberbarium or clathrate Xe actions as well as its applications on various bioobjects with anaerobic - red blood cells (RBCs) and aerobic (skin fragments) metabolism. Xe clathrates and hyperbarium storage were simulated under 277 K and 620-725 k...... to control (15.68 ± 1.11, CI95%). Skin fragments were harvested from rat tails and divided on hyberbarium, clathrate and dimetylsulfoxide cryopreserved as control group and stored for 7 days. Assessment was performed by point-score method including epidermal-dermal integrity various assays and engraftment...

  15. 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...

  16. Stretching of red blood cells at high strain rates

    Science.gov (United States)

    Mancuso, J. E.; Ristenpart, W. D.

    2017-10-01

    Most work on the mechanical behavior of red blood cells (RBCs) in flow 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 Rapid Communication, 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 both the Kelvin-Voigt and Skalak viscoelastic models capture the observed stretching dynamics, up to strain rates as high as 2000 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.

  17. Adaptation of red cell enzymes and intermediates in metabolic disorders.

    Science.gov (United States)

    Goebel, K M; Goebel, F D; Neitzert, A; Hausmann, L; Schneider, J

    1975-01-01

    The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

  18. 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.

  19. 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.

  20. Atypical Red Blood Cells Are Prevalent in California Sea Lion Pups Born during Anomalous Sea Surface Temperature Events.

    Science.gov (United States)

    Flores-Morán, Adriana; Banuet-Martínez, Marina; Elorriaga-Verplancken, Fernando R; García-Ortuño, Luis Enrique; Sandoval-Sierra, Julieta; Acevedo-Whitehouse, Karina

    To date, there is limited knowledge of the effects that abnormal sea surface temperature (SST) can have on the physiology of neonate pinnipeds. However, maternal nutritional deficiencies driven by alimentary restrictions would expectedly impact pinniped development and fitness, as an adequate supply of nutrients is essential for growth and proper functioning of all body systems, including red blood cell synthesis and clearance. Here, we investigated red blood cell morphology of California sea lion (CSL) pups from the San Benito Archipelago born during the 2014 and 2015 anomalously high SST events recorded in the northeastern Pacific Ocean. We examined whether atypical erythrocyte morphologies were more common in 2015, when the high SST event was more pronounced, and whether the stable isotope signature of pup fur, as an indicator of maternal feeding strategies, accounted for the number of atypical cells. Various atypical erythrocyte morphologies were more prevalent and more abundant than reference values. Evidence of iron deficiency was found in both years, and only pups born in 2014 showed evidence of active erythropoiesis. Microcytes and reticulocytes were more common in pups with higher isotopic δ 13 C and lower δ 15 N values, suggesting a probable relationship between maternal feeding strategies and the effect of climatic anomalies on red blood cell physiology of their pups. As developing pinnipeds require increased oxygen storage capacity for diving and foraging, the presence of atypical erythrocytes could be relevant to CSL pup fitness if the underlying cause is not reverted. This study is a first step to explore the effects that climatic alterations in the marine environment can have on the blood physiology of developing individuals.

  1. 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.

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

    Science.gov (United States)

    de Back, Djuna Z; Kostova, Elena B; van Kraaij, Marian; van den Berg, Timo K; van Bruggen, Robin

    2014-01-01

    Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 10(10) RBC 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.

  3. Comparative study on the effect of radiation on whole blood and isolate red blood cells

    International Nuclear Information System (INIS)

    Selim, N.S.

    2009-01-01

    Assessment of the dielectric properties of red blood cells requires several steps for preparation and isolation from whole blood. These steps may results in changes in the cells properties, and they are time consuming . The present study aims to compare the properties of both whole blood and isolated red blood cells and the effect of gamma radiation on these properties. Adult male rats were exposed to 1, 3.5 and 7 Gy as single dose, from Cs-137 source.The studies dielectric properties, in the frequency range 40 k Hz to 5 MHz, and light scattering studies for suspensions of whole blood and isolated red blood cells from the same groups were measured. The obtained results showed that whole blood and red blood cells suspensions followed the same trend in their response to radiation, which suggests the possibility of using whole blood suspension for the evaluation of the red blood cells properties

  4. Density increment and decreased survival of rat red blood cells induced by cadmium

    International Nuclear Information System (INIS)

    Kunimoto, M.; Miura, T.

    1986-01-01

    Male Wistar rats were injected with CdCl 2 subcutaneously to examine in vivo effects of Cd on density and survival of red blood cells. During the 7 days after administration of 1.0 mg Cd/kg, the following sequence of events occurred: (1) a progressive increase in the amount of more dense red blood cells concomitant with a decrease in that of light red blood cells from the first to the third day; (2) an increase in the spleen weight at the third day; (3) a decrease in the hematocrit value and an increase in the amount of light red blood cells at the fifth day; and (4) a recovery of the hematocrit value at the seventh day. Five days after administration, the hematocrit value decreased in a dose-dependent mode and the decrease was significant at the 1% level at 1.0 and 1.5 mg Cd/kg. A highly significant splenomegaly was also observed at 0.5 to 1.5 mg Cd/kg. In order to label red blood cells in vivo, [ 3 H] diisopropylfluorophosphate ([ 3 H]DFP) was injected into rats. At Day 11, Cd at either 0.5 or 1.0 mg/kg was administered to [ 3 H]DFP-prelabeled animals. Cd administration accelerated 3 H-labeled red cell clearance from the blood. Six days after Cd administration, the radioactivity of red blood cells was 76 and 68% of the control at 0.5 and 1.0 mg Cd/kg, respectively. In vitro treatment of rat red density and accelerated in vivo clearance of red blood cells from the recipient circulation. These results show that Cd at low dose can cause anemia by increasing red cell density and by accelerating red cell sequestration, presumably in the spleen

  5. 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.

  6. Pre-Clinical Cell-Based Therapy for Limbal Stem Cell Deficiency.

    Science.gov (United States)

    Sehic, Amer; Utheim, Øygunn Aass; Ommundsen, Kristoffer; Utheim, Tor Paaske

    2015-08-28

    The cornea is essential for normal vision by maintaining transparency for light transmission. Limbal stem cells, which reside in the corneal periphery, contribute to the homeostasis of the corneal epithelium. Any damage or disease affecting the function of these cells may result in limbal stem cell deficiency (LSCD). The condition may result in both severe pain and blindness. Transplantation of ex vivo cultured cells onto the cornea is most often an effective therapeutic strategy for LSCD. The use of ex vivo cultured limbal epithelial cells (LEC), oral mucosal epithelial cells, and conjunctival epithelial cells to treat LSCD has been explored in humans. The present review focuses on the current state of knowledge of the many other cell-based therapies of LSCD that have so far exclusively been explored in animal models as there is currently no consensus on the best cell type for treating LSCD. Major findings of all these studies with special emphasis on substrates for culture and transplantation are systematically presented and discussed. Among the many potential cell types that still have not been used clinically, we conclude that two easily accessible autologous sources, epidermal stem cells and hair follicle-derived stem cells, are particularly strong candidates for future clinical trials.

  7. Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase

    Directory of Open Access Journals (Sweden)

    Yuanqing Gao

    2018-01-01

    Conclusions: Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism.

  8. An electronic apparatus for early detection of changes in red cell ...

    African Journals Online (AJOL)

    An electronic apparatus was developed for anaesthetists to use to detect changes in red cell concentration during surgery. The mechanism is based on the relationship between the red cell content and the electrical conductivity of blood. In a pilot study of 170 blood samples, a correlation coefficient of 0,9806 was obtained ...

  9. An electronic apparatus for early detection of changes in red cell ...

    African Journals Online (AJOL)

    1989-08-19

    Aug 19, 1989 ... An electronic apparatus was developed for anaesthetists to use to detect changes in red cell concentration during sur- gery. The mechanism is based on the relationship between the red cell content and the electrical conductivity of blood. In a pilot study of 170 blood samples, a correlation coefficient.

  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. Light scattering by red blood cells in ektacytometry: Fraunhofer versus anomalous diffraction

    NARCIS (Netherlands)

    Streekstra, G. J.; Hoekstra, A. G.; Nijhof, E. J.; Heethaar, R. M.

    1993-01-01

    In the present literature on ektacytometry, small angle light scattering by ellipsoidal red blood cells is commonly approximated by Fraunhofer diffraction. Calculations on a sphere with the size and relative refractive index of a red cell, however, show that Fraunhofer diffraction deviates

  12. Optically-driven red blood cell rotor in linearly polarized laser tweezers

    Indian Academy of Sciences (India)

    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 ...

  13. The Red Blood Cell Membrane of Preterm Infants in the Early Neonatal Period

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2014-01-01

    Full Text Available Objective: to study the nanostructure of red blood cell membranes and erythrocyte index in preterm neonatal infants.Subjects and methods. The trial enrolled 47 neonatal infants, including 33 preterm infants who were included in a study group and 14 fullterm infants who formed a comparative group. The gestational age of the preterm infants was 33.3±1.9 weeks and the birth weight was 2065.4±304.8 g. Red blood cell counts, hemoglobin, and erythrocyte indices were estimat ed and the red blood cells were examined using an atomicforce microscope.Results. At birth, the preterm infants showed macrocytosis, intrauterine poikylocytosis, and the impaired nanostructure of red blood cell membranes. Intrauterine hypoxia affects the red blood cell membrane nanostructures: a phospholipid bilayer and a spectrin matrix, without damaging the membrane protein component. The detected changes are reversible and directed to maintaining the functional ability of red blood cells in a critical situation. At birth, gestational age, a baby's weight, hemoglobin, and blood cholesterol and standard bicarbonate levels influence the parameters of a red blood cell component. The early neonatal period was characterized by an active process on the red blood cell membranes and a change of morphological forms, suggesting the continuing postnatal rearrangement of erythropoiesis and a preterm infant's adaptation to new environmental conditions.

  14. prevalence of iron deficiency in children with cyanotic heart disease

    African Journals Online (AJOL)

    2009-12-01

    Dec 1, 2009 ... ... bone marrow to produce more red cells in an effort to increase the body's oxygen ... so the production of more and more red cells goes unabated leading to ... of iron deficiency was calculated as proportion of children with ...

  15. The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

    International Nuclear Information System (INIS)

    Abbasi, Rashda; Efferth, Thomas; Kuhmann, Christine; Opatz, Till; Hao, Xiaojiang; Popanda, Odilia; Schmezer, Peter

    2012-01-01

    Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC 50 values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol was the most effective compound with a difference of > 1000-fold in resistance between normal and NER-deficient cells (IC 50 values for cells with deficiency in ERCC6: 0.15 μM, XPC: 0.18 μM, and normal cells: > 180 μM). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. -- Highlights: ► Thousand-fold higher Ascaridol activity in NER-deficient versus proficient cells. ► Impaired repair of Ascaridol-induced oxidative DNA damage in NER-deficient cells. ► Selective activity of Ascaridol opens new therapy options in

  16. The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Rashda [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Efferth, Thomas [Institute of Pharmacy und Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Kuhmann, Christine [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Opatz, Till [Institute of Organic Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz (Germany); Hao, Xiaojiang [Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204 (China); Popanda, Odilia, E-mail: o.popanda@dkfz.de [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Schmezer, Peter [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2012-03-15

    Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC{sub 50} values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol was the most effective compound with a difference of > 1000-fold in resistance between normal and NER-deficient cells (IC{sub 50} values for cells with deficiency in ERCC6: 0.15 μM, XPC: 0.18 μM, and normal cells: > 180 μM). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. -- Highlights: ► Thousand-fold higher Ascaridol activity in NER-deficient versus proficient cells. ► Impaired repair of Ascaridol-induced oxidative DNA damage in NER-deficient cells. ► Selective activity of Ascaridol opens new therapy

  17. 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

  18. 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

  19. Mechanical properties of stored red blood cells using optical tweezers

    Science.gov (United States)

    Fontes, Adriana; Alexandre de Thomaz, Andre; de Ysasa Pozzo, Liliana; de Lourdes Barjas-Castro, Maria; Brandao, Marcelo M.; Saad, Sara T. O.; Barbosa, Luiz Carlos; Cesar, Carlos Lenz

    2005-08-01

    We have developed a method for measuring the red blood cell (RBC) membrane overall elasticity μ by measuring the deformation of the cells when dragged at a constant velocity through a plasma fluid by an optical tweezers. The deformability of erythrocytes is a critical determinant of blood flow in the microcirculation. We tested our method and hydrodynamic models, which included the presence of two walls, by measuring the RBC deformation as a function of drag velocity and of the distance to the walls. The capability and sensitivity of this method can be evaluated by its application to a variety of studies, such as, the measurement of RBC elasticity of sickle cell anemia patients comparing homozygous (HbSS), including patients taking hydroxyrea (HU) and heterozygous (HbAS) with normal donors and the RBC elasticity measurement of gamma irradiated stored blood for transfusion to immunosupressed patients as a function of time and dose. These studies show that the technique has the sensitivity to discriminate heterozygous and homozygous sickle cell anemia patients from normal donors and even follow the course of HU treatment of Homozygous patients. The gamma irradiation studies show that there is no significant change in RBC elasticity over time for up to 14 days of storage, regardless of whether the unit was irradiated or not, but there was a huge change in the measured elasticity for the RBC units stored for more than 21 days after irradiation. These finds are important for the assessment of stored irradiated RBC viability for transfusion purposes because the present protocol consider 28 storage days after irradiation as the limit for the RBC usage.

  20. Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death.

    Science.gov (United States)

    Chou, Susan S; Clegg, Michael S; Momma, Tony Y; Niles, Brad J; Duffy, Jodie Y; Daston, George P; Keen, Carl L

    2004-10-01

    Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1-C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-alpha, whereas PKC-alpha phosphorylation was not altered. Inhibition of PKC-alpha with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-delta, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-delta fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-delta inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-delta, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-delta to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.

  1. 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.

  2. effect of thermal stress of short duration on the red blood cell

    African Journals Online (AJOL)

    Dr Ivanc

    2013-05-01

    May 1, 2013 ... of red blood cell count (RBC), haemoglobin concentration, packed cell volume ... The temperature at which stress begins to occur ..... of Barton (2002) that PCV is a measure of the cellular ..... Tufts B (eds) Fish respiration.

  3. Fetal red blood cell parameters in thalassemia and hemoglobinopathies.

    Science.gov (United States)

    Karnpean, Rossarin; Fucharoen, Goonnapa; Fucharoen, Supan; Ratanasiri, Thawalwong

    2013-01-01

    With the lack of fetal blood specimens in routine practice, little is known about red blood cell (RBC) parameters of fetuses with various thalassemia syndromes. This study aimed to describe these in various forms of thalassemia. The study was performed on 93 fetal blood specimens obtained from pregnant women by cordocentesis during 18-24 weeks of gestation. RBC parameters were recorded on automated analyzer. Hemoglobin (Hb) and DNA analyses were performed for definite genotyping. No significant difference in RBC parameters was observed between non-thalassemic fetuses and those with β-thalassemia trait, Hb E trait, homozygous Hb E and β-thalassemia/Hb E disease. However, in those with α(0)-thalassemia trait and double heterozygous α(0)-thalassemia/Hb E, slight reduction in mean corpuscular volume (MCV) was noted. Fetuses with the Hb H disease showed significant reductions in Hb, MCV and mean corpuscular Hb (MCH). Marked reductions in Hb, hematocrit, MCH and mean cell Hb concentration and increased RBC distribution width with numerous nucleated RBC were clearly observed in Hb Bart's hydrops fetalis. Simple analysis of fetal RBC parameters is useful for making presumptive prenatal diagnosis of α-thalassemia syndromes including Hb H disease and Hb Bart's hydrops fetalis which can then be confirmed by Hb and DNA analyses. Copyright © 2013 S. Karger AG, Basel.

  4. Thermal analysis of cryoprotective solutions for red blood cells.

    Science.gov (United States)

    Iijima, T

    1998-05-01

    A differential scanning calorimeter was used to study the thermal behavior of glycerol-water solutions (binary system) and the more complex glycerol-based cryoprotective solutions that are used clinically in order to examine the cryoprotective role of glycerol in preserving frozen red blood cells. The melting and glass transition temperatures for the clinically used cryoprotective solutions were as expected, based on the nonequilibriumphase diagram for cryoprotective solutions incorporating isotonic phosphate-buffered saline. Two zones were identified in which solidification occurred without the formation of ice crystals: a glassy state that is crystallographically amorphous was found for glycerol concentrations between 40 and 55% in the binary system and between 45 and 60% in the complex system; a glassy state in the complete absence of ice was found at glycerol concentrations greater than 55% for the binary system or 60% for the complex system. In clinical practice, cryoprotectants are used at initial concentrations lower than those at which these two glassy states occur but there is an increase in the effective glycerol concentration inside and outside the cells as ice forms during the freezing process.

  5. Reduction of prion infectivity in packed red blood cells

    International Nuclear Information System (INIS)

    Morales, Rodrigo; Buytaert-Hoefen, Kimberley A.; Gonzalez-Romero, Dennisse; Castilla, Joaquin; Hansen, Eric T.; Hlavinka, Dennis; Goodrich, Raymond P.; Soto, Claudio

    2008-01-01

    The link between a new variant form of Creutzfeldt-Jakob disease (vCJD) and the consumption of prion contaminated cattle meat as well as recent findings showing that vCJD can be transmitted by blood transfusion have raised public health concerns. Currently, a reliable test to identify prions in blood samples is not available. The purpose of this study was to evaluate the possibility to remove scrapie prion protein (PrP Sc ) and infectivity from red blood cell (RBC) suspensions by a simple washing procedure using a cell separation and washing device. The extent of prion removal was assessed by Western blot, PMCA and infectivity bioassays. Our results revealed a substantial removal of infectious prions (≥3 logs of infectivity) by all techniques used. These data suggest that a significant amount of infectivity present in RBC preparations can be removed by a simple washing procedure. This technology may lead to increased safety of blood products and reduce the risk of further propagation of prion diseases.

  6. Vitamin E nanoemulsion activity on stored red blood cells.

    Science.gov (United States)

    Silva, C A L; Azevedo Filho, C A; Pereira, G; Silva, D C N; Castro, M C A B; Almeida, A F; Lucena, S C A; Santos, B S; Barjas-Castro, M L; Fontes, A

    2017-06-01

    Stored red blood cells (RBCs) undergo numerous changes that have been termed RBC storage lesion, which can be related to oxidative damage. Vitamin E is an important antioxidant, acting on cell lipids. Thus, this study aimed to investigate vitamin E activity on stored RBCs. We prepared a vitamin E nanoemulsion that was added to RBC units and stored at 4 °C. Controls, without vitamin E, were kept under the same conditions. Reactive oxygen species (ROS) production was monitored for up to 35 days of storage. RBC elasticity was also evaluated using an optical tweezer system. Vitamin E-treated samples presented a significant decrease in ROS production. Additionally, the elastic constant for vitamin E-treated RBCs did not differ from the control. Vitamin E decreased the amount of ROS in stored RBCs. Because vitamin E acts on lipid oxidation, results suggest that protein oxidation should also be considered a key factor for erythrocyte elastic properties. Thus, further studies combining vitamin E with protein antioxidants deserve attention, aiming to better preserve overall stored RBC properties. © 2017 British Blood Transfusion Society.

  7. Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

    Directory of Open Access Journals (Sweden)

    Jens Danielczok

    2017-03-01

    Full Text Available Background: Cation channels play an essential role in red blood cells (RBCs ion homeostasis. One set of ion channels are the transient receptor potential channels of canonical type (TRPC channels. The abundance of these channels in primary erythroblasts, erythroid cell lines and RBCs was associated with an increase in intracellular Ca2+ upon stimulation with Erythropoietin (Epo. In contrast two independent studies on Epo-treated patients revealed diminished basal Ca2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet. Methods: To resolve the seemingly conflicting reports we challenged mature human and mouse RBCs of several genotypes with Epo and Prostaglandin E2 (PGE2 and recorded the intracellular Ca2+ content. Next Generation Sequencing was utilised to approach a molecular analysis of reticulocytes. Results/Conclusions: Our results allow concluding that Epo and PGE2 regulation of the Ca2+ homeostasis is distinctly different between murine and human RBCs and that changes in intracellular Ca2+ upon Epo treatment is a primary rather than a compensatory effect. In human RBCs, Epo itself has no effect on Ca2+ fluxes but inhibits the PGE2-induced Ca2+ entry. In murine mature RBCs functional evidence indicates TRPC4/C5 mediated Ca2+ entry activated by Epo whereas PGE2 leads to a TRPC independent Ca2+ entry.

  8. 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

  9. In vivo regeneration of red cell 2,3-diphosphoglycerate following transfusion of DPG-depleted AS-1, AS-3 and CPDA-1 red cells.

    Science.gov (United States)

    Heaton, A; Keegan, T; Holme, S

    1989-01-01

    Regeneration of 2,3-diphosphoglycerate (DPG) was determined following transfusion of DPG-depleted group O red cells into group A recipients. Blood from five donors was stored in the adenine-containing solutions CPDA-1, AS-1 or AS-3 for 35 d at 4 degrees C. Post-transfusion red cell DPG and ATP were measured in separated group O red cells over a 7 d period. The studies confirmed rapid in vivo DPG regeneration with greater than or equal to 50% of the maximum level being achieved within 7 h. An average of 95% of the recipients' pre-transfusion DPG level was achieved by 72 h and by 7 d mean (+/- SEM) DPG levels relative to recipient's pre-transfusion DPG averaged 84% (+/- 13%), 92% (+/- 17%) and 84% (+/- 21%) for CPDA-1, AS-1 and AS-3 red cells, respectively. Results were comparable to those previously reported for blood stored in ACD for 15-20 d (Valeri & Hirsch, 1969; Beutler & Wood, 1969). The immediate regeneration rate, V, closely approximated first order regeneration kinetics with AS-3 red cells exhibiting double the rate of CPDA-1 red cells (P less than 0.001). AS-1 red cells exhibited an intermediate rate of regeneration which was not significantly different compared to either CPDA-1 or AS-3 (P greater than 0.05). V exhibited a significant (P less than 0.05) positive correlation with ATP levels 5-7 h post-infusion. ATP regeneration of the infused cells was rapid with a mean increase of 1.2 mumol/g Hb above post-storage levels being achieved 1 h following transfusion.

  10. An enzyme-linked immunoabsorbent assay for estimating red cell survival of transfused red cells-validation using CR-51 labeling

    International Nuclear Information System (INIS)

    Drew, H.; Kickler, T.; Smith, B.; LaFrance, N.

    1984-01-01

    The survival time of transfused red cells antigenically distinct from the recipient's red cells was determined using an indirect enzyme linked antiglobulin test. These results were then compared to those determined by Cr-51 labeling. Three patients with hypoproliferative anemias and one patient (2 studies) with traumatic hemolytic anemia caused by a prosthetic heart valve were studied. Survival times were performed by transfusing a 5cc aliquot of Cr-51 labeled cells along with the remaining unit. One hour post transfusion, a blood sample was drawn and used as the 100% value. Subsequent samples drawn over a 2-3 week period were then compared to the initial sample to determine percent survival for both methods. The ELISA method for measuring red cell survival in antigenically distinct cells is in close agreement with the Cr-51 method. Although CR-51 labeling is the accepted method for red cell survival determination the ELISA method can be used when radioisotopes are unavailable or contraindicated or when the decision to estimate red cell survival is made after transfusion

  11. 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

  12. Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation.

    Science.gov (United States)

    Rubin, Olivier; Delobel, Julien; Prudent, Michel; Lion, Niels; Kohl, Kid; Tucker, Erik I; Tissot, Jean-Daniel; Angelillo-Scherrer, Anne

    2013-08-01

    Red blood cell-derived microparticles (RMPs) are small phospholipid vesicles shed from RBCs in blood units, where they accumulate during storage. Because microparticles are bioactive, it could be suggested that RMPs are mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent. This study was performed to establish the impact on coagulation of RMPs isolated from blood units. Using calibrated automated thrombography, we investigated whether RMPs affect thrombin generation (TG) in plasma. We found that RMPs were not only able to increase TG in plasma in the presence of a low exogenous tissue factor (TF) concentration, but also to initiate TG in plasma in absence of exogenous TF. TG induced by RMPs in the absence of exogenous TF was neither affected by the presence of blocking anti-TF nor by the absence of Factor (F)VII. It was significantly reduced in plasma deficient in FVIII or F IX and abolished in FII-, FV-, FX-, or FXI-deficient plasma. TG was also totally abolished when anti-XI 01A6 was added in the sample. Finally, neither Western blotting, flow cytometry, nor immunogold labeling allowed the detection of traces of TF antigen. In addition, RMPs did not comprise polyphosphate, an important modulator of coagulation. Taken together, our data show that RMPs have FXI-dependent procoagulant properties and are able to initiate and propagate TG. The anionic surface of RMPs might be the site of FXI-mediated TG amplification and intrinsic tenase and prothrombinase complex assembly. © 2012 American Association of Blood Banks.

  13. The restoration in vivo of 2,3-diphosphoglycerate (2,3-DPG) in stored red cells, after transfusion. The levels of red cells 2,3-DPG.

    Science.gov (United States)

    Stan, Ana; Zsigmond, Eva

    2009-01-01

    Since the main reason for transfusing preserved red cells is to increase the oxygen carrying capacity of the recipient, the circulating preserved red cells should have at the time of transfusion normal oxygen uptake and normal oxyhemoglobin dissociation characteristics. We evaluated the effectiveness of transfused red cells, through periodical determination of erythrocyte components, during 72 hours after transfusions of large quantities (3,000 mL) of blood. Three patients with massive hemorrhages, two after amputation and one after nephrectomy were given each 3,000 mL preserved blood (in ACD, 10 days, at 4 degrees C). Red cell 2,3-DPG and serum inorganic phosphorus were determined prior to transfusion and after, periodically, for three days. Red cell 2,3-DPG was determined by Krimsky's method and inorganic phosphorus by Kuttner and Lichtenstein's method. The in vivo restoration of 2,3-DPG--of transfused red cells is shown as a percentage of recipient's final 2,3-DPG level, and was calculated in each of the three patients. The level of erythrocyte 2,3-DPG was greater than 60% of the final level within 24 hours, after the end of transfusion. The in vivo rates of restoration of 2,3-DPG in transfused red cells for periods of 0-6, 6-24, 24-48 and 48-72 hours are 0.251, 0.238, 0.133, 0.120 mM/L cells/hour. The therapeutic significance of the increased oxygen affinity of stored blood becomes very important in clinical conditions, when large volumes of red cells are urgently needed. After massive transfusions, the restoration of 2,3-DPG in red cells produces a decrease of serum inorganic phosphorus through its consumption. The stored blood with low values of erythrocyte 2,3-DPG can be used without hesitation when correcting a chronic anemia for instance, but in acute situation, when the organism needs restoration of the oxygen releasing capacity within minutes, the resynthesis is obviously insufficient. In such situations, fresh blood or blood with a near normal 2,3-DPG

  14. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

    Science.gov (United States)

    Cohen, Philip R

    2017-03-22

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  15. Squamous cell carcinoma in association with a red tattoo.

    Science.gov (United States)

    Schmitz, Inge; Prymak, Oleg; Epple, Matthias; Ernert, Carsten; Tannapfel, Andrea

    2016-06-01

    Although tattoos have become exceedingly popular in recent years, only few cases of severe reactions leading to malignant transformation have been reported in the literature. This stands in contrast to the virtually innumerable number of tattoos worldwide. The composition of tattoo dyes is highly variable, and even the same colors may contain different compounds. The objective of our study was to investigate in what way tattoo dyes may potentially trigger skin cancer. We report the rare case of a 24-year-old woman who - seven months after getting a tattoo on the back of her foot - developed a squamous cell carcinoma in close proximity to the red dye used. Complications started in the form of nonspecific swelling. The lesion was histologically examined. The composition of the incorporated dye was analyzed using scanning electron microscopy in combination with energy dispersive element analysis. Thermogravimetry and powder diffraction were used for further characterization. While the tattoo dye primarily consisted of barium sulfate, traces of Al, S, Ti, P, Mg, and Cl were also detected. The analysis showed pigment granules of varying sizes. In rare cases, tattoo inks may have carcinogenic effects, which appear to be multifactorial. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  16. 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.

  17. Zeroing in on red blood cell unit expiry.

    Science.gov (United States)

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

    2017-12-01

    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.

  18. Centrifugation-free washing: A novel approach for removing immunoglobulin A from stored red blood cells.

    Science.gov (United States)

    Vörös, Eszter; Piety, Nathaniel Z; Strachan, Briony C; Lu, Madeleine; Shevkoplyas, Sergey S

    2018-08-01

    Washed red blood cells (RBCs) are indicated for immunoglobulin A (IgA) deficient recipients. Centrifugation-based cell processors commonly used by hospital blood banks cannot consistently reduce IgA below the recommended levels, hence double washing is frequently required. Here, we describe a prototype of a simple, portable, disposable system capable of washing stored RBCs without centrifugation, while reducing IgA below 0.05 mg/dL in a single run. Samples from RBC units (n = 8, leukoreduced, 4-6 weeks storage duration) were diluted with normal saline to a hematocrit of 10%, and then washed using either the prototype washing system, or via conventional centrifugation. The efficiency of the two washing methods was quantified and compared by measuring several key in vitro quality metrics. The prototype of the washing system was able to process stored RBCs at a rate of 300 mL/hour, producing a suspension of washed RBCs with 43 ± 3% hematocrit and 86 ± 7% cell recovery. Overall, the two washing methods performed similarly for most measured parameters, lowering the concentration of free hemoglobin by >4-fold and total free protein by >10-fold. Importantly, the new washing system reduced the IgA level to 0.02 ± 0.01 mg/mL, a concentration 5-fold lower than that produced by conventional centrifugation. This proof-of-concept study showed that centrifugation may be unnecessary for washing stored RBCs. A simple, disposable, centrifugation-free washing system could be particularly useful in smaller medical facilities and resource limited settings that may lack access to centrifugation-based cell processors. © 2017 Wiley Periodicals, Inc.

  19. 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....

  20. 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

    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...... 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...... and their genetically identical wild-type controls. For future studies, this cell system can be used to uncover the mechanisms and signalling pathways involved in the TIMP-1-mediated inhibition of apoptosis as well as to investigate the possibility of using TIMP-1 inhibitors to optimise the effect of conventional...

  1. Mechanisms of radiosensitization and protection studied with glutathione-deficient human cell lines

    International Nuclear Information System (INIS)

    Revesz, L.; Edgren, M.

    1982-01-01

    Glutathione-deficient fibroblasts and lymphoblastoid cells, derived from patients with an inborn error of glutathione synthetase activity, and glutathione-proficient cells, derived from clinically healthy individuals, were used to investigate the importance of glutathione for radiosensitization by misonidazole. With single-strand DNA breaks as an end point, misonidazole as well as oxygen was found to lack any sensitizing effect on cells deficient in glutathione. The post-irradiation repair of single-strand breaks induced by hypoxic irradiation of misonidazole treated cells was found to be a great extent glutathione dependent, like the repair of breaks induced by oxic irradiation. Naturally occurring aminothiols in glutathione-deficient cells appeared to be in efficient as substitutes for glutatione. Artificial aminothiols, such as cysteamine or dithiothreitol, were found to effectively replace glutathione

  2. 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...

  3. Survival of red blood cells after transfusion: processes and consequences

    Directory of Open Access Journals (Sweden)

    Giel eBosman

    2013-12-01

    Full Text Available The currently available data suggest that efforts towards improving the quality of red blood cell (RBC blood bank products should concentrate on: (1 preventing the removal of a considerable fraction of the transfused RBCs that takes place within the first hours after transfusion; (2 minimizing the interaction of the transfused RBCs with the patient's immune system. These issues are important in reducing the number and extent of the damaging side effects of transfusions, such as generation of alloantibodies and autoantibodies and iron accumulation, especially in transfusion-dependent patients. Thus, it becomes important for blood bank research not only to assess the classical RBC parameters for quality control during storage, but even more so to identify the parameters that predict RBC survival, function and behaviour in the patient after transfusion. These parameters are likely to result from elucidation of the mechanisms that underly physiological RBC aging in vivo, and that lead to the generation of senescent cell antigens and the accumulation of damaged molecules in vesicles. Also, study of RBC pathology-related mechanisms, such as encountered in various hemoglobinopathies and membranopathies, may help to elucidate the mechanisms underlying a storage-associated increase in susceptibility to physiological stress conditions. Recent data indicate that a combination of new approaches in vitro to mimick RBC behaviour in vivo, the growing knowledge of the signaling networks that regulate RBC structure and function, and the rapidly expanding set of proteomic and metabolomic data, will be instrumental to identify the storage-associated processes that control RBC survival after transfusion.

  4. Influence of red blood cell-derived microparticles upon vasoregulation.

    Science.gov (United States)

    Said, Ahmed S; Doctor, Allan

    2017-10-01

    Here we review recent data and the evolving understanding of the role of red blood cell-derived microparticles (RMPs) in normal physiology and in disease progression. Microparticles (MPs) are small membrane vesicles derived from various parent cell types. MPs are produced in response to a variety of stimuli through several cytoskeletal and membrane phospholipid changes. MPs have been investigated as potential biomarkers for multiple disease processes and are thought to have biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in apoptosis. Specifically, RMPs are produced normally during RBC maturation and their production is accelerated during processing and storage for transfusion. Several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs from that of intact RBCs, and the nature and composition of RMP components are affected by both storage duration and the character of storage solutions. Recognised RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion, as well as influence upon vasoregulation via nitric oxide (NO) scavenging. Of particular relevance, RMPs are more avid NO scavengers than intact RBCs and this feature has been proposed as a mechanism for the impaired oxygen delivery homeostasis that has been observed following transfusion. Preliminary human studies demonstrate that circulating RMP abundance increases with RBC transfusion and is associated with altered plasma vasoactivity and abnormal vasoregulation. In summary, RMPs are submicron particles released from stored RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in transfusion recipients is an area of continued

  5. Red cell-derived microparticles (RMP) as haemostatic agent.

    Science.gov (United States)

    Jy, Wenche; Johansen, Max E; Bidot, Carlos; Horstman, Lawrence L; Ahn, Yeon S

    2013-10-01

    Among circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 µm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.

  6. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice

    International Nuclear Information System (INIS)

    Bix, M.; Nanshih Liao; Raulet, D.; Zijlstra, M.; Loring, J.; Jaenisch, R.

    1991-01-01

    Irradiated MHC-heterozygous mice often reject bone marrow cells transplanted from one of the homozygous parental strains, a phenomenon ('hybrid resistance') that appears to violate the laws of transplantation. Rejection of parental and allogeneic marrow cells also differs from conventional T cell-mediated rejection mechanisms as it is effected by NK1.1 + cells. To account for the unusual specificity of bone marrow rejection, it has been proposed that NK1.1 + cells destroy marrow cells that fail to express the full complement of self MHC class I (MHC-I) molecules. We show here that NK1.1 + cells in normal mice reject haemopoietic transplants from mice that are deficient for normal cell-surface MHC-I expression because of a targeted mutation in the β 2 -microglobulin gene. These findings demonstrate that deficient expression of MHC-I molecules renders marrow cells susceptible to rejection. (author)

  7. Algorithm for detection of overlapped red blood cells in microscopic images of blood smears

    OpenAIRE

    Romero-Rondón, Miguel Fabián; Sanabria-Rosas, Laura Melissa; Bautista-Rozo, Lola Xiomara; Mendoza-Castellanos, Alfonso

    2016-01-01

    The hemogram is one of the most requested medical tests as it presents details about the three cell series in the blood: red series, white series and platelet series. To make some diagnostics, the specialist must undertake the test manually, observing the blood cells under the microscope, which implies a great physical effort. In order to facilitate this work, different digital image processing techniques to detect and classify red blood cells have been proposed. However, a common problem is ...

  8. A comparison of methods of determining the 100 percent survival of preserved red cells

    International Nuclear Information System (INIS)

    Valeri, C.R.; Pivacek, L.E.; Ouellet, R.; Gray, A.

    1984-01-01

    Studies were done to compare three methods to determine the 100 percent survival value from which to estimate the 24-hour posttransfusion survival of preserved red cells. The following methods using small aliquots of 51 Cr-labeled autologous preserved red cells were evaluated: First, the 125 I-albumin method, which is an indirect measurement of the recipient's red cell volume derived from the plasma volume measured using 125 I-labeled albumin and the total body hematocrit. Second, the body surface area method (BSA) in which the recipient's red cell volume is derived from a body surface area nomogram. Third, an extrapolation method, which extrapolates to zero time the radioactivity associated with the red cells in the recipient's circulation from 10 to 20 or 15 to 30 minutes after transfusion. The three methods gave similar results in all studies in which less than 20 percent of the transfused red cells were nonviable (24-hour posttransfusion survival values of between 80-100%), but not when more than 20 percent of the red cells were nonviable. When 21 to 35 percent of the transfused red cells were nonviable (24-hour posttransfusion survivals of 65 to 79%), values with the 125 I-albumin method and the body surface area method were about 5 percent lower (p less than 0.001) than values with the extrapolation method. When greater than 35 percent of the red cells were nonviable (24-hour posttransfusion survival values of less than 65%), values with the 125 I-albumin method and the body surface area method were about 10 percent lower (p less than 0.001) than those obtained by the extrapolation method

  9. 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.

  10. An Inducible, Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

    Science.gov (United States)

    Bailis, Julie M.; Gordon, Marcia L.; Gurgel, Jesse L.; Komor, Alexis C.; Barton, Jacqueline K.; Kirsch, Ilan R.

    2013-01-01

    The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. PMID:24205301

  11. Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ning Li

    2017-01-01

    Full Text Available The red blood cell distribution width (RDW obtained from a standard complete blood count (CBC is a convenient and inexpensive biochemical parameter representing the variability in size of circulating erythrocytes. Over the past few decades, RDW with mean corpuscular volume (MCV has been used to identify quite a few hematological system diseases including iron-deficiency anemia and bone marrow dysfunction. In recent years, many clinical studies have proved that the alterations of RDW levels may be associated with the incidence and prognosis in many cardiovascular and cerebrovascular diseases (CVDs. Therefore, early detection and intervention in time of these vascular diseases is critical for delaying their progression. RDW as a new predictive marker and an independent risk factor plays a significant role in assessing the severity and progression of CVDs. However, the mechanisms of the association between RDW and the prognosis of CVDs remain unclear. In this review, we will provide an overview of the representative literatures concerning hypothetical and potential epidemiological associations between RDW and CVDs and discuss the underlying mechanisms.

  12. Influence of zinc deficiency on cell-membrane fluidity in Jurkat, 3T3 and IMR-32 cells.

    Science.gov (United States)

    Verstraeten, Sandra V; Zago, M Paola; MacKenzie, Gerardo G; Keen, Carl L; Oteiza, Patricia I

    2004-01-01

    We investigated whether zinc deficiency can affect plasma membrane rheology. Three cell lines, human leukaemia T-cells (Jurkat), rat fibroblasts (3T3) and human neuroblastoma cells (IMR-32), were cultured for 48 h in control medium, in zinc-deficient medium (1.5 microM zinc; 1.5 Zn), or in the zinc-deficient medium supplemented with 15 microM zinc (15 Zn). The number of viable cells was lower in the 1.5 Zn group than in the control and 15 Zn groups. The frequency of apoptosis was higher in the 1.5 Zn group than in the control and 15 Zn groups. Membrane fluidity was evaluated using the 6-(9-anthroyloxy)stearic acid and 16-(9-anthroyloxy)palmitic acid probes. Membrane fluidity was higher in 1.5 Zn cells than in the control cells; no differences were observed between control cells and 15 Zn cells. The effect of zinc deficiency on membrane fluidity at the water/lipid interface was associated with a higher phosphatidylserine externalization. The higher membrane fluidity in the hydrophobic region of the bilayer was correlated with a lower content of arachidonic acid. We suggest that the increased fluidity of the membrane secondary to zinc deficiency is in part due to a decrease in arachidonic acid content and the apoptosis-related changes in phosphatidylserine distribution. PMID:14629198

  13. Effect of high dose irradiation on the red cell span in rabbits

    International Nuclear Information System (INIS)

    Kang, T.W.; Koh, J.W.; Woo, K.S.; Lee, O.H.; Youn, C.S.

    1982-01-01

    As a part of studies on acute effects of high dose irradiation in vivo, the present report was carried out to evaluate the changes of the red cell life span in the white rabbits by a single whole body exposure to gamma rays from 60 Co teletherapy unit. The exposure was done in dose levels of 100, 600 and 900 rads to each experimental group of 10 rabbits. The life span apparent half survival time of red cells, and that the red cell volume in the circulting blood were measured by ICSH Reference method using 51 Cr. (Author)

  14. Clinical Utility of Red Cell Distribution Width in Alcoholic and Non-alcoholic Liver Cirrhosis

    OpenAIRE

    Milić, Sandra; Mikolašević, Ivana; Radić, Mladen; Hauser, Goran; Štimac, Davor

    2011-01-01

    Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as a part of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We re...

  15. Bone scan and red blood cell scan in a patient with epidermal naevus syndrome

    International Nuclear Information System (INIS)

    Becker, W.; Wolf, F.; Stosiek, N.; Peters, K.P.

    1990-01-01

    A bone scan and red blood cell scan in the rare epidermal naevus syndrome, associated with multiple haemangiomes of the bone and hypophosphataemic osteomalacia in a 20-year-old man are reported. The typical pattern of osteomalacia on the bone scan was associated with lesions of increased bone metabolism in the peripheral bones. The haemangiomas did not pool labelled red blood cells. Thus, the bone scan seems to be suited for diagnosing the complete extent of haemangiomas in bone, but they could not be specifically proven by red blood cell pooling. (orig.)

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

  17. Tc-99m-labeled red blood cells for the measurement of red cell mass in newborn infants: concise communication

    International Nuclear Information System (INIS)

    Linderkamp, O.; Betke, K.; Fendel, H.; Klemm, J.; Lorenzen, K.; Riegel, K.P.

    1980-01-01

    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

  18. Role of red cells and plasma composition on blood sessile droplet evaporation

    Science.gov (United States)

    Lanotte, Luca; Laux, Didier; Charlot, Benoît; Abkarian, Manouk

    2017-11-01

    The morphology of dried blood droplets derives from the deposition of red cells, the main components of their solute phase. Up to now, evaporation-induced convective flows were supposed to be at the base of red cell distribution in blood samples. Here, we present a direct visualization by videomicroscopy of the internal dynamics in desiccating blood droplets, focusing on the role of cell concentration and plasma composition. We show that in diluted suspensions, the convection is promoted by the rich molecular composition of plasma, whereas it is replaced by an outward red blood cell displacement front at higher hematocrits. We also evaluate by ultrasounds the effect of red cell deposition on the temporal evolution of sample rigidity and adhesiveness.

  19. The morphological classification of normal and abnormal red blood cell using Self Organizing Map

    Science.gov (United States)

    Rahmat, R. F.; Wulandari, F. S.; Faza, S.; Muchtar, M. A.; Siregar, I.

    2018-02-01

    Blood is an essential component of living creatures in the vascular space. For possible disease identification, it can be tested through a blood test, one of which can be seen from the form of red blood cells. The normal and abnormal morphology of the red blood cells of a patient is very helpful to doctors in detecting a disease. With the advancement of digital image processing technology can be used to identify normal and abnormal blood cells of a patient. This research used self-organizing map method to classify the normal and abnormal form of red blood cells in the digital image. The use of self-organizing map neural network method can be implemented to classify the normal and abnormal form of red blood cells in the input image with 93,78% accuracy testing.

  20. 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.

  1. Human and great ape red blood cells differ in plasmalogen levels and composition.

    Science.gov (United States)

    Moser, Ann B; Steinberg, Steven J; Watkins, Paul A; Moser, Hugo W; Ramaswamy, Krishna; Siegmund, Kimberly D; Lee, D Rick; Ely, John J; Ryder, Oliver A; Hacia, Joseph G

    2011-06-17

    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. 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. 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 rodents with plasmalogen disorders, we propose that cross

  2. 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

  3. Increased phorbol 12,13-dibutyrate (PDBu) receptor function associated with sickle red cell membrane ghosts

    International Nuclear Information System (INIS)

    Ramachandran, M.; Nair, C.N.; Abraham, E.C.

    1987-01-01

    The biological receptor for tumor-promoting phorbol esters has been identified as the Ca 2+ /phospholipid dependent enzyme, protein kinase C. In the red cell, this enzyme is mainly cytosolic but becomes translocated to the membrane if the cellular Ca 2+ is allowed to rise. Since cellular Ca 2+ in sickle red cells is high, it was reasoned that this enzyme may become more membrane-bound. In fact, the authors noticed a four-fold increase in the binding of 3 H-PDBu by membrane ghosts isolated from sickle red cells compared to normal red cells (pmoles PDBu bound/mg protein; normal = 0.3 vs sickle cell = 1.4). Attempts to assay the enzyme directly as phospholipid-activated 32 P incorporation into the acid-precipitable membrane proteins also indicated a two-fold increase in the radiolabelling of sickle cell membrane ghosts. Autophosphorylation of membrane proteins and analysis of the phosphorylation profile by SDS-PAGE and autoradiography revealed phosphorylation predominantly of bands 3, 4.1 and 4.9 which are known protein kinase C substrates for the red cell enzyme. The increased membrane-associated protein kinase C in sickle red cells may have a bearing on the altered membrane properties reported in this condition

  4. Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

    International Nuclear Information System (INIS)

    Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K.; Clapp, D. Wade; De Vries, George H.

    2006-01-01

    Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells

  5. Clearance of Giardia muris infection in mice deficient in natural killer cells.

    OpenAIRE

    Heyworth, M F; Kung, J E; Eriksson, E C

    1986-01-01

    Immunocompetent C57BL/6J mice and beige mice (which are deficient in natural killer cells) were infected with Giardia muris. Both types of mice cleared G. muris infection at similar rates. This observation suggests that clearance of G. muris parasites from the mouse intestine is not mediated by natural killer cells.

  6. 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

  7. Studies on sequestration of neuraminidase-treated red blood cells

    International Nuclear Information System (INIS)

    Simchon, S.; Jan, K.M.; Chien, S.

    1988-01-01

    The effects of reduction in the surface charge of red blood cells (RBCs) on regional blood flow and RBC distribution were studied in rats anesthetized with pentobarbital sodium. RBCs were treated with neuraminidase to reduce their electrophoretic mobility by 56%. Normal and neuraminidase-treated RBCs labeled with 51Cr or 111In were injected into a femoral vein while an equal volume of blood was simultaneously withdrawn from a femoral artery. More than 70% of the neuraminidase-treated RBCs injected disappeared from the circulating blood in 30 min compared with less than 2% of normal RBCs. The relative distributions of neuraminidase-treated RBCs to normal RBCs, as determined from radioactivity counting, were significantly greater than 1 in the spleen (5.65 +/- 0.97, mean +/- SD), the liver (2.84 +/- 0.21), the lung (1.48 +/- 0.31), and the kidney (1.49 +/- 0.27), indicating a preferential trapping of neuraminidase-treated RBCs in these regions. This ratio was approximately 1 in all other organs. Regional blood flows in tissues were determined with 15-micron microspheres in the control period and after the infusion of neuraminidase-treated RBCs (experimental). Experimental-to-control blood flow ratios were 0.40 +/- 0.05 in the spleen, 0.66 +/- 0.06 in the liver, 0.78 +/- 0.03 in the lung, and 0.78 +/- 0.09 in the kidneys; this ratio was approximately 1 in all other organs. An experimental-to-control blood flow ratio less than 1 indicates a reduction in blood flow; this occurred in the same organs as those with trapping of neuraminidase-treated RBCs

  8. Trends in US minority red blood cell unit donations.

    Science.gov (United States)

    Yazer, Mark H; Delaney, Meghan; Germain, Marc; Karafin, Matthew S; Sayers, Merlyn; Vassallo, Ralph; Ziman, Alyssa; Shaz, Beth

    2017-05-01

    To provide the appropriately diverse blood supply necessary to support alloimmunized and chronically transfused patients, minority donation recruitment programs have been implemented. This study investigated temporal changes in minority red blood cell (RBC) donation patterns in the United States. Data on donor race and ethnicity from 2006 through 2015, including the number of unique donors, collections, RBCs successfully donated, and average annual number of RBC donations per donor (donor fraction), were collected from eight US blood collectors. Minority donors were stratified into the following groups: Asian, black or African American, Hispanic or Latino, Native Indian or Alaska Native, Native Hawaiian or other Pacific Islander, white, multiracial/other, and no answer/not sure. Over the 10-year period, white donors annually constituted the majority of unique donors (range, 70.7%-73.9%), had the greatest proportion of collections (range, 76.1%-79.8%), and donated the greatest proportion of RBC units (range, 76.3%-80.2%). These donors also had the highest annual donor fraction (range, 1.82-1.91 units per donor). Black or African American donors annually constituted between 4.9 and 5.2% of all donors during the study period and donated between 4.0 and 4.3% of all RBC units. Linear regression analysis revealed decreasing numbers of donors, collections, and donated RBC units from white donors over time. Although the US population has diversified, and minority recruitment programs have been implemented, white donors constitute the majority of RBC donors and donations. Focused and effective efforts are needed to increase the proportion of minority donors. © 2017 AABB.

  9. Red Blood Cell Mechanical Fragility Test for Clinical Research Applications.

    Science.gov (United States)

    Ziegler, Luke A; Olia, Salim E; Kameneva, Marina V

    2017-07-01

    Red blood cell (RBC) susceptibility to mechanically induced hemolysis, or RBC mechanical fragility (MF), is an important parameter in the characterization of erythrocyte membrane health. The rocker bead test (RBT) and associated calculated mechanical fragility index (MFI) is a simple method for the assessment of RBC MF. Requiring a minimum of 15.5 mL of blood and necessitating adjustment of hematocrit (Ht) to a "standard" value (40%), the current RBT is not suitable for use in most studies involving human subjects. To address these limitations, we propose a 6.5 mL reduced volume RBT and corresponding modified MFI (MMFI) that does not require prior Ht adjustment. This new method was assessed for i) correlation to the existing text, ii) to quantify the effect of Ht on MFI, and iii) validation by reexamining the protective effect of plasma proteins on RBC MF. The reduced volume RBT strongly correlated (r = 0.941) with the established large volume RBT at matched Hts, and an equation was developed to calculate MMFI: a numerical estimation (R 2  = 0.923) of MFI if performed with the reduced volume RBT at "standard" (40%) Ht. An inversely proportional relationship was found between plasma protein concentration and RBC MF using the MMFI-reduced volume method, supporting previous literature findings. The new reduced volume RBT and modified MFI will allow for the measurement of RBC MF in clinical and preclinical studies involving humans or small animals. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  10. Cell envelope stress response in cell wall-deficient L-forms of Bacillus subtilis.

    Science.gov (United States)

    Wolf, Diana; Domínguez-Cuevas, Patricia; Daniel, Richard A; Mascher, Thorsten

    2012-11-01

    L-forms are cell wall-deficient bacteria that can grow and proliferate in osmotically stabilizing media. Recently, a strain of the Gram-positive model bacterium Bacillus subtilis was constructed that allowed controlled switching between rod-shaped wild-type cells and corresponding L-forms. Both states can be stably maintained under suitable culture conditions. Because of the absence of a cell wall, L-forms are known to be insensitive to β-lactam antibiotics, but reports on the susceptibility of L-forms to other antibiotics that interfere with membrane-anchored steps of cell wall biosynthesis are sparse, conflicting, and strongly influenced by strain background and method of L-form generation. Here we investigated the response of B. subtilis to the presence of cell envelope antibiotics, with regard to both antibiotic resistance and the induction of the known LiaRS- and BceRS-dependent cell envelope stress biosensors. Our results show that B. subtilis L-forms are resistant to antibiotics that interfere with the bactoprenol cycle, such as bacitracin, vancomycin, and mersacidin, but are hypersensitive to nisin and daptomycin, which both affect membrane integrity. Moreover, we established a lacZ-based reporter gene assay for L-forms and provide evidence that LiaRS senses its inducers indirectly (damage sensing), while the Bce module detects its inducers directly (drug sensing).

  11. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Directory of Open Access Journals (Sweden)

    Tongfang Tang

    Full Text Available BACKGROUND: Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD through alternation of liver innate immune response. AIMS: The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. METHODS: Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. RESULTS: High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4 expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. CONCLUSION: High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  12. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Science.gov (United States)

    Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

    2013-01-01

    Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  13. Sickle cell test

    Science.gov (United States)

    ... cell anemia Sickle cell trait Iron deficiency or blood transfusions within the past 3 months can cause a " ... slight risk any time the skin is broken) Alternative Names Sickledex; Hgb S test Images Red blood cells, sickle cell Red blood cells, multiple sickle ...

  14. 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.

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... cannot make as many new red blood cells. The red blood cells it does make have less hemoglobin than normal. Hemoglobin is a protein inside red blood cells that carries oxygen from ...

  16. 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

  17. 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.

  18. Method for extending the useful shelf-life of refrigerated red blood cells by flushing with inert gas

    Science.gov (United States)

    Bitensky, M.W.; Yoshida, Tatsuro

    1997-04-29

    A method is disclosed using oxygen removal for extending the useful shelf-life of refrigerated red blood cells. A cost-effective, 4 C storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. Preservation of adenosine triphosphate levels and reduction in hemolysis and in membrane vesicle production of red blood cells stored at 4 C for prolonged periods of time is achieved by removing oxygen from the red blood cells at the time of storage; in particular, by flushing with an inert gas. Adenosine triphosphate levels of the stored red blood cells are boosted in some samples by addition of ammonium phosphate. 4 figs.

  19. Trafficking of cholesterol from cell bodies to distal axons in Niemann Pick C1-deficient neurons.

    Science.gov (United States)

    Karten, Barbara; Vance, Dennis E; Campenot, Robert B; Vance, Jean E

    2003-02-07

    Niemann Pick type C (NPC) disease is a progressive neurodegenerative disorder. In cells lacking functional NPC1 protein, endocytosed cholesterol accumulates in late endosomes/lysosomes. We utilized primary neuronal cultures in which cell bodies and distal axons reside in separate compartments to investigate the requirement of NPC1 protein for transport of cholesterol from cell bodies to distal axons. We have recently observed that in NPC1-deficient neurons compared with wild-type neurons, cholesterol accumulates in cell bodies but is reduced in distal axons (Karten, B., Vance, D. E., Campenot, R. B., and Vance, J. E. (2002) J. Neurochem. 83, 1154-1163). We now show that NPC1 protein is expressed in both cell bodies and distal axons. In NPC1-deficient neurons, cholesterol delivered to cell bodies from low density lipoproteins (LDLs), high density lipoproteins, or cyclodextrin complexes was transported into axons in normal amounts, whereas transport of endogenously synthesized cholesterol was impaired. Inhibition of cholesterol synthesis with pravastatin in wild-type and NPC1-deficient neurons reduced axonal growth. However, LDLs restored a normal rate of growth to wild-type but not NPC1-deficient neurons treated with pravastatin. Thus, although LDL cholesterol is transported into axons of NPC1-deficient neurons, this source of cholesterol does not sustain normal axonal growth. Over the lifespan of NPC1-deficient neurons, these defects in cholesterol transport might be responsible for the observed altered distribution of cholesterol between cell bodies and axons and, consequently, might contribute to the neurological dysfunction in NPC disease.

  20. Glucose-6-phosphate dehydrogenase deficiency; the single most ...

    African Journals Online (AJOL)

    Introduction: Glucose- 6-phosphate dehydrogenase deficiency is the most common enzymatic disorder of the red cell and an important risk factor for neonatal jaundice. Methodology: The aim of the study was to determine the incidence of G-6-PD deficiency among jaundiced neonates, and describe the associated morbidity ...

  1. Effects of 4000 rad irradiation on the in vitro storage properties of packed red cells

    International Nuclear Information System (INIS)

    Moore, G.L.; Ledford, M.E.

    1985-01-01

    Immunosuppressed patients who require red cell transfusions receive irradiated (1500-3000 rad) packed red cells. These cells are irradiated immediately before infusion. If a large group of patients become immunosuppressed due to exposure to radiation or chemicals, the ability to supply large volumes of irradiated blood at the time of use might not be possible. An alternate solution to providing quantities of irradiated blood is to irradiate the units prior to storage. This study presents in vitro data comparing storage of paired packed red cell units either irradiated or not irradiated. Five units of fresh blood drawn into citrate-phosphate-dextrose-adenine (CPDA-1) were packed to a hematocrit of 75 +/- 1 percent, and then each unit was divided in two equal parts. One of each pair was irradiated (4000 rads), and both parts of each unit were stored for 35 days at 4 degrees C. Samples were analyzed every 7 days. Irradiation caused a slight drop in red cell adenosine triphosphate and 2,3 diphosphoglycerate and a slight increase in plasma hemoglobin compared to controls. Methemoglobin, pH, and glucose consumption were identical to the controls. The evidence indicates that irradiation did not cause biochemical or metabolic changes in the red cells that would lead us to suspect a difference between irradiated and nonirradiated stored red cells in function or viability. These negative findings require in vivo confirmation

  2. 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.

  3. Red blood cell transfusions and tissue oxygenation in anemic hematology outpatients

    NARCIS (Netherlands)

    Yuruk, Koray; Bartels, Sebastiaan A.; Milstein, Dan M. J.; Bezemer, Rick; Biemond, Bart J.; Ince, Can

    2012-01-01

    BACKGROUND: There is little clinical evidence that red blood cell (RBC) transfusions improve oxygen availability at the microcirculatory level. We tested the hypotheses that anemia in chronically anemic patients with relatively healthy microcirculation would be associated with low tissue hemoglobin

  4. Specific features of red blood cell morphology in hemolytic disease neonates undergoing intrauterine intravascular blood transfusion

    Directory of Open Access Journals (Sweden)

    A. V. Ivanova

    2016-01-01

    Full Text Available The paper presents data on the characteristics of red blood cell morphology in infants who have undergone intrauterine intravascular blood transfusion for hemolytic disease of the fetus. The infants are shown to have a reduction in the mean volume of red blood cells and in their mean level of hemoglobin, a decrease in the fraction of fetal hemoglobin and an increase in oxygen tension at half saturation. The above morphological characteristics of red blood cells remain decreased during the neonatal period after exchange transfusion or others, as clinically indicated, which seems to suggest that the compensatory-adaptive mechanisms to regulate hematopoiesis are exhausted and a donor’s red blood cells continue to be predominant.

  5. The effect of iron-deficiency anemia on cytolytic activity of mice spleen and peritoneal cells against allogenic tumor cells

    International Nuclear Information System (INIS)

    Kuvibidila, S.R.; Baliga, B.S.; Suskind, R.M.

    1983-01-01

    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 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

  6. Nanostructure of Red Blood Cell Membranes in Premature Neonates with Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2013-01-01

    Full Text Available Objective: to study the nanostructure of red blood cell membranes in premature babies with neonatal respiratory distress syndrome (NRDS, by applying atomic force microscopy. Subjects and methods. The investigation included 27 newborn infants, of them 13 premature babies with NRDS formed a study group. The mean gestational age was 33.1±2.3 weeks; their birth weight was 1800±299.3 g. A comparison group consisted of 14 full-term babies with favorable pregnancy and term labor. The mean gestational age of the babies was 39.4±0.5 weeks; their birth weight was 3131.7±588.8 g; the infants had a one minute Apgar score of 8±0.4. Their red blood cells were examined using an atomic force microscope. The objects to be examined were residual umbilical cord blood (RUCB from the premature infants; central venous blood after 7 hours of birth and neonatal venous blood taken on day 7 of life. Results. RUCB from full-term babies contained planocytes that were a major morphological type of red blood cells. In physiological pregnancy and acute fetal hypoxia, the morphological composition of red blood cells in premature neonates with NRDS was close to that in full-term babies. The planocytes are also a major morphological type of red blood cells in the premature infants; the frequency of their occurrence varies. Stomatocytes are typical of all the neonates in the NRDS group; their frequency levels vary greatly: from 8 to 65% of the total number of erythrocytes. The examination revealed that the premature infants of 31—36 weeks gestation were characterized by abnormal erythrocyte shapes that showed a high variability. At birth, the premature babies were found to have changes in the nanostructure of red blood cell membranes, which were influenced by intrauterine hypoxia. The first-order value reflecting flickering in the red blood cell membrane varies to the most extent. Conclusion. Atomic force microscopy showed that the greatest changes in the structure of red

  7. Mechanical and electrical properties of red blood cells using optical tweezers

    International Nuclear Information System (INIS)

    Fontes, A; Castro, M L Barjas; Brandão, M M; Fernandes, H P; Huruta, R R; Costa, F F; Saad, S T O; Thomaz, A A; Pozzo, L Y; Barbosa, L C; Cesar, C L

    2011-01-01

    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

  8. Liquid Storage at 4 deg C of Previously Frozen Red Cells

    Science.gov (United States)

    1987-12-01

    adenosine tnphosphate (ATP). 2.3- acceptable red cell function. A post-thaw storage ca- diphosphoglycerate (2.3-DPG), glucose, supernatant hemo...and Received for publication September 22. 1986; revision received supernatant hemoglobin levels within the acceptable range, November 29, 1986, and...percent. All units were sterile at the end of the 21-day post- thaw storage period. 6.9 The mean red cell ATP and 2,3-DPG levels are shown in Figure 1

  9. 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.

  10. The effects of red blood cell preparation method on in vitro markers of red blood cell aging and inflammatory response.

    Science.gov (United States)

    Radwanski, Katherine; Garraud, Olivier; Cognasse, Fabrice; Hamzeh-Cognasse, Hind; Payrat, Jean-Marc; Min, Kyungyoon

    2013-12-01

    Studies are currently under way examining whether the age of stored red blood cells (RBCs) affects clinical outcome in transfusion recipients. The effects of storage duration on the RBC storage lesion are well documented, while fewer studies are available regarding the effect of RBC production method. In this study, we compared in vitro RBC quality variables and markers of inflammatory response in apheresis and whole blood (WB)-derived RBCs, specifically those prepared after an overnight room temperature hold (RTH) of WB. SAGM RBCs, prepared from WB after overnight RTH (n = 10), were compared to SAGM RBCs prepared using an apheresis device (Alyx, n = 10). As a control, SAGM RBCs were also prepared within 2 hours of WB collection (2-hr WB, n = 10). All RBCs were stored at 4°C for 42 days with weekly assay of in vitro variables, cytokines and/or chemokines, and neutrophil activation after incubation with RBC supernatant. RTH WB RBCs exhibited decreased levels of 2,3-diphosphoglycerate acid (2.3 μmol/g hemoglobin [Hb] ± 2.1 vs. 13.7 ± 1.3 μmol/g Hb) and morphology (160 ± 10 vs. 192 ± 5) on Day 1 and increased hemolysis (0.45 ± 0.21% vs. 0.31 ± 0.09%) and microparticles (6.1 ± 2.8/10(3) RBCs vs. 3.9 ± 1.1/10(3) RBCs) on Day 42 compared to apheresis RBCs. Gro-α and ENA-78 cytokine levels were significantly higher in RTH WB than Alyx RBCs during storage. CD11b expression was highest in neutrophils exposed to supernatant from RTH WB RBCs (p < 0.05). RBC preparation method has a meaningful effect on the RBC storage lesion, which should be taken into account in addition to length of storage. © 2013 American Association of Blood Banks.

  11. Storage characteristics of multiple-donor pooled red blood cells compared to single-donor red blood cell units.

    Science.gov (United States)

    Mathur, Aabhas; Chowdhury, Raquibul; Hillyer, Christopher D; Mitchell, W Beau; Shaz, Beth H

    2016-12-01

    Each unit of blood donated is processed and stored individually resulting in variability in the amount of red blood cells (RBCs) collected, RBC properties, and the 24-hour posttransfusion RBC survivability. As a result, each unit differs in its ability to deliver oxygen and potentially its effects on the recipient. The goal of this study was to investigate the storage of pooled RBCs from multiple donors in comparison to control standard RBC units. Two units of irradiated, leukoreduced RBCs of same ABO, D, E, C, and K antigen phenotype were collected from each of five donors using apheresis. One unit from each donor was pooled in a 2-L bag and remaining units were used as controls. After being pooled, RBCs were separated in five bags and stored at 4°C along with the controls. Quality indexes were measured on Days 2, 14, and 28 for all the units. Adenosine triphosphate assays for both pooled and controls showed a slight decrease from Day 2 to Day 28 (pooled/control from 5.22/5.24 to 4.35/4.33 µmol/g hemoglobin [Hb]). 2,3-Diphosphoglycerate was successfully rejuvenated for all RBC units on Day 28 (pooled 11.46 µmol/g Hb; control 11.86 µmol/g Hb). The results showed a nonsignificant difference between pooled and control units, with a general trend of lower standard deviation for pooled units when compared to controls. Pooled units have reduced unit-to-unit variability. Future exploration of their immunogenicity is required before using pooled units for transfusion. © 2016 AABB.

  12. Copper deficiency alters cell bioenergetics and induces mitochondrial fusion through up-regulation of MFN2 and OPA1 in erythropoietic cells

    International Nuclear Information System (INIS)

    Bustos, Rodrigo I.; Jensen, Erik L.; Ruiz, Lina M.; Rivera, Salvador; Ruiz, Sebastián; Simon, Felipe; Riedel, Claudia; Ferrick, David; Elorza, Alvaro A.

    2013-01-01

    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

  13. 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.

  14. The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia.

    Science.gov (United States)

    Al Balushi, Halima W M; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

    2018-03-01

    Red cells from patients with sickle cell anemia (SCA) are under greater oxidative challenge than those from normal individuals. We postulated that oxidants generated by xanthine oxidase (XO) and hypoxanthine (HO) contribute to the pathogenesis of SCA through altering solute permeability. Sickling, activities of the main red cell dehydration pathways (P sickle , Gardos channel, and KCl cotransporter [KCC]), and cell volume were measured at 100, 30, and 0 mmHg O 2 , together with deoxygenation-induced nonelectrolyte hemolysis. Unexpectedly, XO/HO mixtures had mainly inhibitory effects on sickling, P sickle , and Gardos channel activities, while KCC activity and nonelectrolyte hemolysis were increased. Gardos channel activity was significantly elevated in red cells pharmacologically loaded with Ca 2+ using the ionophore A23187, consistent with an effect on the transport system per se as well as via Ca 2+ entry likely via the P sickle pathway. KCC activity is controlled by several pairs of conjugate protein kinases and phosphatases. Its activity, however, was also stimulated by XO/HO mixtures in red cells pretreated with N-ethylmaleimide (NEM), which is thought to prevent regulation via changes in protein phosphorylation, suggesting that the oxidants formed could also have direct effects on this transporter. In the presence of XO/HO, red cell volume was better maintained in deoxygenated red cells. Overall, the most notable effect of XO/HO mixtures was an increase in red cell fragility. These findings increase our understanding of the effects of oxidative challenge in SCA patients and are relevant to the behavior of red cells in vivo. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  15. Iron Deficiency in Seagrasses and Macroalgae in the Red Sea Is Unrelated to Latitude and Physiological Performance

    KAUST Repository

    Anton, Andrea; Hendriks, Iris E.; Marbà , Nú ria; Krause-Jensen, Dorte; Garcias Bonet, Neus; Duarte, Carlos M.

    2018-01-01

    Iron can limit primary production in shallow marine systems, especially in tropical waters characterized by carbonated sediments, where iron is largely trapped in a non-available form. The Red Sea, an oligotrophic ecosystem characterized by a strong N-S latitudinal nutrient gradient, is a suitable setting to explore patterns in situ of iron limitation in macrophytes and their physiological performance under different iron regimes. We assessed the interactions between environmental gradients and physiological parameters of poorly-studied Red Sea macrophytes. Iron concentration, chlorophyll a concentration, blade thickness, and productivity of 17 species of macrophytes, including seven species of seagrasses and 10 species of macroalgae, were measured at 21 locations, spanning 10 latitude degrees, along the Saudi Arabian coast. Almost 90% of macrophyte species had iron concentrations below the levels indicative of iron sufficiency and more than 40% had critically low iron concentrations, suggesting that iron is a limiting factor of primary production throughout the Red Sea. We did not identify relationships between tissue iron concentration, chlorophyll a concentration and physiological performance of the 17 species of seagrass and macroalgae. There was also no latitudinal pattern in any of the parameters studied, indicating that the South to North oligotrophication of the Red Sea is not reflected in iron concentration, chlorophyll a concentration or productivity of Red Sea macrophytes.

  16. Iron Deficiency in Seagrasses and Macroalgae in the Red Sea Is Unrelated to Latitude and Physiological Performance

    KAUST Repository

    Anton, Andrea

    2018-03-06

    Iron can limit primary production in shallow marine systems, especially in tropical waters characterized by carbonated sediments, where iron is largely trapped in a non-available form. The Red Sea, an oligotrophic ecosystem characterized by a strong N-S latitudinal nutrient gradient, is a suitable setting to explore patterns in situ of iron limitation in macrophytes and their physiological performance under different iron regimes. We assessed the interactions between environmental gradients and physiological parameters of poorly-studied Red Sea macrophytes. Iron concentration, chlorophyll a concentration, blade thickness, and productivity of 17 species of macrophytes, including seven species of seagrasses and 10 species of macroalgae, were measured at 21 locations, spanning 10 latitude degrees, along the Saudi Arabian coast. Almost 90% of macrophyte species had iron concentrations below the levels indicative of iron sufficiency and more than 40% had critically low iron concentrations, suggesting that iron is a limiting factor of primary production throughout the Red Sea. We did not identify relationships between tissue iron concentration, chlorophyll a concentration and physiological performance of the 17 species of seagrass and macroalgae. There was also no latitudinal pattern in any of the parameters studied, indicating that the South to North oligotrophication of the Red Sea is not reflected in iron concentration, chlorophyll a concentration or productivity of Red Sea macrophytes.

  17. Identification and red blood cell automated counting from blood smear images using computer-aided system.

    Science.gov (United States)

    Acharya, Vasundhara; Kumar, Preetham

    2018-03-01

    Red blood cell count plays a vital role in identifying the overall health of the patient. Hospitals use the hemocytometer to count the blood cells. Conventional method of placing the smear under microscope and counting the cells manually lead to erroneous results, and medical laboratory technicians are put under stress. A computer-aided system will help to attain precise results in less amount of time. This research work proposes an image-processing technique for counting the number of red blood cells. It aims to examine and process the blood smear image, in order to support the counting of red blood cells and identify the number of normal and abnormal cells in the image automatically. K-medoids algorithm which is robust to external noise is used to extract the WBCs from the image. Granulometric analysis is used to separate the red blood cells from the white blood cells. The red blood cells obtained are counted using the labeling algorithm and circular Hough transform. The radius range for the circle-drawing algorithm is estimated by computing the distance of the pixels from the boundary which automates the entire algorithm. A comparison is done between the counts obtained using the labeling algorithm and circular Hough transform. Results of the work showed that circular Hough transform was more accurate in counting the red blood cells than the labeling algorithm as it was successful in identifying even the overlapping cells. The work also intends to compare the results of cell count done using the proposed methodology and manual approach. The work is designed to address all the drawbacks of the previous research work. The research work can be extended to extract various texture and shape features of abnormal cells identified so that diseases like anemia of inflammation and chronic disease can be detected at the earliest.

  18. Professional killer cell deficiencies and decreased survival in pulmonary arterial hypertension.

    Science.gov (United States)

    Edwards, Adrienne L; Gunningham, Sarah P; Clare, Geoffrey C; Hayman, Matthew W; Smith, Mark; Frampton, Christopher M A; Robinson, Bridget A; Troughton, Richard W; Beckert, Lutz E L

    2013-11-01

    Increasing evidence implicates lymphocytes in pulmonary arterial hypertension (PAH) pathogenesis. Rats deficient in T-lymphocytes show increased propensity to develop PAH but when injected with endothelial progenitor cells are protected from PAH (a mechanism dependent on natural killer (NK) cells). A decreased quantity of circulating cytotoxic CD8+ T-lymphocytes and NK cells are now reported in PAH patients; however, the effect of lymphocyte depletion on disease outcome is unknown. This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide (BNP) levels of patients with idiopathic PAH (IPAH), connective tissue disease-associated PAH (CTD-APAH) and matched healthy controls. Lymphocyte surface markers studied include: CD4+ (helper T-cell marker), CD8+ (cytotoxic T-cell marker), CD56/CD16 (NK cell marker) and CD19+ (mature B-cell marker). Lymphocyte deficiencies and plasma BNP levels were then correlated with clinical outcome. Fourteen patients with PAH (9 IPAH, 5CTD) were recruited. Three patients were deceased at 1-year follow-up; all had elevated CD4 : CD8 ratios and deficiencies of NK cells and cytotoxic CD8+ T-lymphocytes at recruitment. Patients with normal lymphocyte profiles at recruitment were all alive a year later, and none were on the active transplant list. As univariate markers, cytotoxic CD8+ T-cell and NK cell counts were linked to short-term survival. Deficiencies in NK cells and cytotoxic CD8+ T-cells may be associated with an increased risk of death in PAH patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  19. Differential programming of B cells in AID deficient mice.

    Directory of Open Access Journals (Sweden)

    Marc A Hogenbirk

    Full Text Available The Aicda locus encodes the activation induced cytidine deaminase (AID and is highly expressed in germinal center (GC B cells to initiate somatic hypermutation (SHM and class switch recombination (CSR of immunoglobulin (Ig genes. Besides these Ig specific activities in B cells, AID has been implicated in active DNA demethylation in non-B cell systems. We here determined a potential role of AID as an epigenetic eraser and transcriptional regulator in B cells. RNA-Seq on different B cell subsets revealed that Aicda(-/- B cells are developmentally affected. However as shown by RNA-Seq, MethylCap-Seq, and SNP analysis these transcriptome alterations may not relate to AID, but alternatively to a CBA mouse strain derived region around the targeted Aicda locus. These unexpected confounding parameters provide alternative, AID-independent interpretations on genotype-phenotype correlations previously reported in numerous studies on AID using the Aicda(-/- mouse strain.

  20. Acute and chronic influence of temperature on red blood cell anion exchange.

    Science.gov (United States)

    Jensen, F B; Wang, T; Brahm, J

    2001-01-01

    Unidirectional (36)Cl(-) efflux via the red blood cell anion exchanger was measured under Cl(-) self-exchange conditions (i.e. no net flow of anions) in rainbow trout Oncorhynchus mykiss and red-eared freshwater turtle Trachemys scripta to examine the effects of acute temperature changes and acclimation temperature on this process. We also evaluated the possible adaptation of anion exchange to different temperature regimes by including our previously published data on other animals. An acute temperature increase caused a significant increase in the rate constant (k) for unidirectional Cl(-) efflux in rainbow trout and freshwater turtle. After 3 weeks of temperature acclimation, 5 degrees C-acclimated rainbow trout showed only marginally higher Cl(-) transport rates than 15 degrees C-acclimated trout when compared at the same temperature. Apparent activation energies for red blood cell Cl(-) exchange in trout and turtle were lower than values reported in endothermic animals. The Q(10) for red blood cell anion exchange was 2.0 in trout and 2.3 in turtle, values close to those for CO(2) excretion, suggesting that, in ectothermic animals, the temperature sensitivity of band-3-mediated anion exchange matches the temperature sensitivity of CO(2) transport (where red blood cell Cl(-)/HCO(3)(-) exchange is a rate-limiting step). In endotherms, such as man and chicken, Q(10) values for red blood cell anion exchange are considerably higher but are no obstacle to CO(2) transport, because body temperature is normally kept constant at values at which anion exchange rates are high. When compared at constant temperature, red blood cell Cl(-) permeability shows large differences among species (trout, carp, eel, cod, turtle, alligator, chicken and man). Cl(-) permeabilities are, however, remarkable similar when compared at preferred body temperatures, suggesting an appropriate evolutionary adaptation of red blood cell anion exchange function to the different thermal niches occupied

  1. Mathematical analysis of 51Cr-labelled red cell survival curves in congenital haemolytic anaemias

    International Nuclear Information System (INIS)

    Kasfiki, A.G.; Antipas, S.E.; Dimitriou, P.A.; Gritzali, F.A.; Melissinos, K.G.

    1982-01-01

    The parameters of 51 Cr labelled red cell survival curves were calculated in 26 patients with homozygous β-thalassaemia, 8 with sickle-cell anaemia and 3 with s-β-thalassaemia, using a non-linear weighted least squares analysis computer program. In thalassaemic children the calculated parameters denote that the shorting of the mean cell life is due to early senescence alone, while there is some evidence that in thalassaemic adults additional extracellular destruction mechanisms participate as well. Red cell survival curves from patients with sickle-cell anaemia and s-β-thalassaemia resemble each other, while their parameters indicate an initial rapid loss of radioactivity, early senescence and the presence of extracellular red cell destruction factors. (orig.)

  2. Radio-sensitization of WRN helicase deficient cancer cells by targeting homologous recombination pathway

    International Nuclear Information System (INIS)

    Gupta, Pooja; Saha, Bhaskar; Patro, Birija Sankar; Chattopadhyay, Subrata

    2016-01-01

    Ionizing radiation (IR) induced DNA double-strand breaks (DSBs) are primarily repaired by non-homologous end joining (NHEJ). However, it is well established that a subset DSBs which are accumulated in IR-induced G2 phase are dependent on homologous recombination (HR). DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyperdependent on DNA damage response pathways, including the CHK1-kinase-mediated HR-repair. These observations suggest that DNA repair deficient tumors should exhibit increased radio-sensitivity under HR inhibition. Genetic defects leading to functional loss of werner (WRN) protein is associated with genomic instability and increased cancer incidence. WRN function is known to be abrogated in several human cancer cells due to hypermethylation of CpGisland-promoter and transcriptional silencing of WRN gene. In the current investigation, using isogenic pairs of cell lines differing only in the WRN function, we showed that WRN-deficient cell lines were hyper-radiosensitive to CHK1 pharmacologic inhibition. Here, we found that unrepaired DSB was drastically increased in WRN-deficient cells vis-à-vis WRN-proficient cells in response to IR and CHK1 inhibitor (CHK1i). Our results revealed a marginal role of NHEJ pathway accountable for the radio-sensitivity of WRN-deficient cells. Interestingly, silencing CTIP, a HR protein required for RAD51 loading, significantly abrogated the CHK1i-mediated radiosensitivity in WRN-deficient cells. Silencing of WRN or CTIP individually led to no significant difference in the extent of DNA end resection, as required during HR pathway. Imperatively, our results revealed that WRN and CTIP together play a complementary role in executing DNA end resection during HR-mediated repair of IR induced DSBs. Altogether, our data indicated that inhibition of IR-induced HR pathway at RAD51 loading, but not at DSB end resection, make the WRN-deficient cancer cells

  3. 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.

  4. Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

    OpenAIRE

    Joiner, C H; Platt, O S; Lux, S E

    1986-01-01

    The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blo...

  5. Red blood cell transfusion in infants and children - Current perspectives.

    Science.gov (United States)

    Ali, Natasha

    2018-06-01

    Children routinely receive packed red blood transfusion when they are admitted in the intensive care unit or undergoing cardiac surgeries. These guidelines aim to summarize literature and provide transfusion triggers exclusively in infants and children. Copyright © 2017. Published by Elsevier B.V.

  6. RISK OF RED BLOOD CELL ALLOIMMUNISATION IN RWANDA ...

    African Journals Online (AJOL)

    2013-04-04

    Apr 4, 2013 ... spin crossmatch (IS-XM) or indirect antiglobulin test crossmatch (IAT-XM). Objectives: ... with an odds ratio of 4.8; [95% CI=1.2-19.8]; and a p-value of 0.031. Conclusion: ... formation of single or multiple antibodies to red blood.

  7. 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.

  8. Nile Red Staining for Oil Determination in Microalgal Cells: A New Insight through Statistical Modelling

    Directory of Open Access Journals (Sweden)

    Ronald Halim

    2015-01-01

    Full Text Available In the wake of global warming and rapid fossil fuel depletion, microalgae emerge as promising feedstocks for sustainable biofuel production. Nile red staining acts as a rapid diagnostic tool to measure the amount of biodiesel-convertible lipid that the cells accumulate. There is a need for the development of a more uniform staining procedure. In its first phase, this study examined the dependence of microalgal Nile red fluorescence (Tetraselmis suecica in terms of its most pertinent staining variables. A quadratic surface model that successfully described the Nile red fluorescence intensity as a composite function of its variables was generated (r2=0.86. Cell concentration was shown to have a significant effect on the fluorescence intensity. Up to a certain threshold, fluorescence intensity was shown to increase with Nile red dye concentration. In its second phase, the study reviewed findings from previous Nile red studies to elucidate some of the fundamental mechanism underlying the diffusion of Nile red dye molecules into the microalgal cells and their subsequent interaction with intracellular lipids. Through the review process, we were able to develop a simple framework that provided a set of guidelines for the standardization of the Nile red staining procedure across different microalgal species.

  9. Red blood cell phenotype prevalence in blood donors who self-identify as Hispanic

    DEFF Research Database (Denmark)

    Sheppard, Chelsea A; Bolen, Nicole L; Eades, Beth

    2017-01-01

    CONCLUSIONS: Molecular genotyping platforms provide a quick, high-throughput method for identifying red blood cell units for patients on extended phenotype-matching protocols, such as those with sickle cell disease or thalassemia. Most of the antigen prevalence data reported are for non-Hispanic ......CONCLUSIONS: Molecular genotyping platforms provide a quick, high-throughput method for identifying red blood cell units for patients on extended phenotype-matching protocols, such as those with sickle cell disease or thalassemia. Most of the antigen prevalence data reported are for non...

  10. Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1.

    Science.gov (United States)

    Hinrichsen, Inga; Ernst, Benjamin Philipp; Nuber, Franziska; Passmann, Sandra; Schäfer, Dieter; Steinke, Verena; Friedrichs, Nicolaus; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

    2014-01-24

    Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.

  11. Partial Red Blood Cell Exchange in Children and Young Patients with Sickle Cell Disease: Manual Versus Automated Procedure.

    Science.gov (United States)

    Escobar, Carlos; Moniz, Marta; Nunes, Pedro; Abadesso, Clara; Ferreira, Teresa; Barra, António; Lichtner, Anabela; Loureiro, Helena; Dias, Alexandra; Almeida, Helena

    2017-10-31

    The benefits of manual versus automated red blood cell exchange have rarely been documented and studies in young sickle cell disease patients are scarce. We aim to describe and compare our experience in these two procedures. Young patients (≤ 21 years old) who underwent manual- or automated-red blood cell exchange for prevention or treatment of sickle cell disease complications were included. Clinical, technical and hematological data were prospectively recorded and analyzed. Ninety-four red blood cell exchange sessions were performed over a period of 68 months, including 57 manual and 37 automated, 63 for chronic complications prevention, 30 for acute complications and one in the pre-operative setting. Mean decrease in sickle hemoglobin levels was higher in automated-red blood cell exchange (p exchange and access alarm on automated-red blood cell exchange. No major complication or alloimunization was recorded. Automated-red blood cell exchange decreased sickle hemoglobin levels more efficiently than manual procedure in the setting of acute and chronic complications of sickle cell disease, with minor technical concerns mainly due to vascular access. The threshold of sickle hemoglobin should be individualized for clinical and hematological goals. In our cohort of young patients, the need for an acceptable venous access was a limiting factor, but iron-overload was avoided. Automated red blood cell exchange is safe and well tolerated. It permits a higher sickle hemoglobin removal efficacy, better volume status control and iron-overload avoidance.

  12. Effect of laser light on the fragility and permeability of the red blood cell membrane

    International Nuclear Information System (INIS)

    El-Yassin, H. D.

    2005-01-01

    The resistance of red blood cells to hypotonic hemolysis is often characterized in terms of their osmotic fragility. The percentage of cells that hemolize when plotted as a function of different concentrations of NaCl forms fragility curve, which has a sigmoidal shape. In this study we show that the exposure of red blood cells to laser light converts the sigmoidal shape of the fragility curve to a hyperbolic one, which means that the old population of the red blood cells are the ones more affected by the light which cause their destruction. At the same time it seems that transport across the cell membrane is affected also. The biochemical and physiological implications of this finding are discussed. (author)

  13. 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

  14. 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.

  15. 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.

  16. Normal mast cell numbers in the tissues of AhR-deficient mice.

    Science.gov (United States)

    Pilz, Caroline; Feyerabend, Thorsten; Sonner, Jana; Redaelli, Chiara; Peter, Katharina; Kunze, Anja; Haas, Katharina; Esser, Charlotte; Schäkel, Knut; Wick, Wolfgang; Rodewald, Hans-Reimer; Lanz, Tobias V; Platten, Michael

    2016-01-01

    The transcription factor aryl hydrocarbon receptor (AhR) acts as an immunomodulatory molecule in several immune cell lineages. Recently, it has been implicated in development and maintenance of immune cells in barrier tissues such as skin and mucosa. To investigate its role on mast cell development and maintenance in skin, peritoneal exudate cells (PECs) and lymph nodes, we studied in depth their phenotype in AhR-deficient mice. Our findings do not provide any evidence for a suspected role of the AhR in mast cell homeostasis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.

    Directory of Open Access Journals (Sweden)

    Ryo Kurita

    Full Text Available Transfusion of red blood cells (RBCs is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.

  18. An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency.

    Science.gov (United States)

    Melek, Engin; Bulut, Fatma Derya; Atmış, Bahriye; Yılmaz, Berna Şeker; Bayazıt, Aysun Karabay; Mungan, Neslihan Önenli

    2017-02-01

    Carnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the β-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury.

  19. Immunospecific red cell binding of iodine 125-labeled immunoglobulin G erythrocyte autoantibodies

    International Nuclear Information System (INIS)

    Masouredis, S.P.; Branks, M.J.; Garratty, G.; Victoria, E.J.

    1987-01-01

    The primary interaction of autoantibodies with red cells has been studied by using labeled autoantibodies. Immunoglobulin G red cell autoantibodies obtained from IgG antiglobulin-positive normal blood donors were labeled with radioactive iodine and compared with alloanti-D with respect to their properties and binding behavior. Iodine 125 -labeled IgG autoantibody migrated as a single homogeneous peak with the same relative mobility as human IgG on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric focusing pattern of labeled autoantibodies varied from donor to donor but was similar to that of alloanti-D, consisting of multiple IgG populations with isoelectric points in the neutral to alkaline range. 125 I-autoantibody bound to all human red cells of common Rh phenotypes. Evidence for immunospecific antibody binding of the labeled autoantibody was based on variation in equilibrium binding to nonhuman and human red cells of common and rare phenotypes, enhanced binding after red cell protease modification, antiglobulin reactivity of cell-bound IgG comparable to that of cell-bound anti-D, and saturation binding in autoantibody excess. Scatchard analysis of two 125 I-autoantibody preparations yielded site numbers of 41,500 and 53,300 with equilibrium constants of 3.7 and 2.1 X 10(8) L X mol-1. Dog, rabbit, rhesus monkey, and baboon red cells were antigen(s) negative by quantitative adsorption studies adsorbing less than 3% of the labeled autoantibody. Reduced ability of rare human D--red blood cells to adsorb the autoantibody and identification of donor autoantibodies that bind to Rh null red blood cells indicated that eluates contained multiple antibody populations of complex specificities in contrast to anti-D, which consists of a monospecific antibody population. Another difference is that less than 70% of the autoantibody IgG was adsorbed by maximum binding red blood cells as compared with greater than 85% for alloanti-D

  20. Patient with pure red cell aplasia who was exposed to the atomic bomb near the site of blast

    Energy Technology Data Exchange (ETDEWEB)

    Toyoda, N; Matsukuma, G; Uchiyama, E; Tsunoo, S; Anpi, S [Nagasaki Atomic Bomb Hospital (Japan)

    1976-03-01

    This paper describes a female patient who had been exposed at the age of 26 to the atomic bomb at a distance of 1.3 km from the bombed area. She was pointed out to have anemia and the disturbance of the liver in 1961. In 1963, she had iron deficiency, hypoleucocytosis, and hyper-..gamma.. globulinemia, and showed a high value of serum colloids. In 1969, she had more frequently anemia together with hyper ..gamma..-globulinemia. The erythrocyte sedimentation rate and serum colloids were still high. The positive reaction to the LE cells began to appear. The liver biopsy findings showed proliferation of Kupper cells in the lobule, decidual degeneration of some liver cells, infiltration of many round cells in the Glisson's sheath. Therefore, she was diagnosed as having pure red cell aplasia and lupoid hepatitis. However, in 1970 she was suspected of having pulmonary valvular insufficiency caused by pulmonary hypertension in spite of the continuous steroid therapy. In 1974, she died of jundice, hyper-..gamma..-globulinemia which accompanied urea in the blood and the increased values of nitrogen and NH/sub 3/. This patient was considered to be interested on the assumption of the relationships between exposure to the atomic bomb and disturbance of immunity.

  1. 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...

  2. 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.

  3. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    International Nuclear Information System (INIS)

    Oommen, Deepu; Yiannakis, Dennis; Jha, Awadhesh N.

    2016-01-01

    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.

  4. 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.

  5. γ-ray dose rate effect in DNA double-strand break repair deficient murine cells

    International Nuclear Information System (INIS)

    Li Liya; Li Peiwen

    2002-01-01

    Objective: To analyze the dose rate effect and potentially lethal damage repair in DNA double-strand break repair deficient murine cells (SCID) irradiated by γ-ray. Methods: The wild type (CB.17+/+) and SCID cells were exposed to γ-ray at high and low dose rates. The high dose rate exposure was fractionated into two equal doses at 24 h intervals. The survival rates of irradiated cells were calculated by clone-forming analysis. Results: When γ-ray was given to wild type (CB.17+/+) cells in two fractions at 24 h intervals, the survival rate was significantly higher than that when the same total dose was given singly. In contrast, there was no difference in the survival rates between the single and fractionated exposure in SCID cells. SCID cells were more sensitive than CB.17+/+ cells to both low and high dose rates γ-ray exposure for cell killing. The survival rate by low dose rate exposure was significantly higher than that by high dose rate exposure, not only in CB.17+/+ cells but also in SCID cells. Conclusions: SCID cells are deficient in repairing γ-ray induced double-strand breaks. There is dose rate effect in both SCID and CB.17+/+ cells

  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. Increased numbers of spleen colony forming units in B cell deficient CBA/N mice

    International Nuclear Information System (INIS)

    Wiktor-Jedrzejczak, W.; Krupienicz, A.; Scher, I.

    1986-01-01

    The formation of exogenous and endogenous spleen colonies was studied in immune-defective mice expressing the CBA/N X-linked xid gene. Bone marrow and spleen cells of immune deficient mice formed increased numbers of eight-day exogenous spleen colonies when transferred to either normal or B cell deficient lethally irradiated recipients. Moreover, defective mice showed increased formation of five-day endogenous spleen colonies (derived from transient endogenous colony forming units; T-CFU) and of ten-day endogenous spleen colonies (derived from CFU-S). Among the possible mechanisms responsible for the observed effects, the most probable appears the one in which decreased numbers of B cell precursors stimulate stem cell pools through a feedback mechanism. (orig.) [de

  8. MSH3-deficiency initiates EMAST without oncogenic transformation of human colon epithelial cells.

    Directory of Open Access Journals (Sweden)

    Christoph Campregher

    Full Text Available BACKGROUND/AIM: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently controversial whether EMAST is associated with oncogenic properties in humans, specifically as cancer development in Msh3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. METHODS: HCT116 and HCT116+chr3 (both MSH3-deficient and primary human colon epithelial cells (HCEC, MSH3-wildtype were stably transfected with an EGFP-based reporter plasmid for the detection of frameshift mutations within an [AAAG]17 repeat. MSH3 was silenced by shRNA and changes in protein expression were analyzed by shotgun proteomics. Colony forming assay was used to determine oncogenic transformation and double strand breaks (DSBs were assessed by Comet assay. RESULTS: Despite differential MLH1 expression, both HCT116 and HCT116+chr3 cells displayed comparable high mutation rates (about 4×10(-4 at [AAAG]17 repeats. Silencing of MSH3 in HCECs leads to a remarkable increased frameshift mutations in [AAAG]17 repeats whereas [CA]13 repeats were less affected. Upon MSH3-silencing, significant changes in the expression of 202 proteins were detected. Pathway analysis revealed overexpression of proteins involved in double strand break repair (MRE11 and RAD50, apoptosis, L1 recycling, and repression of proteins involved in metabolism, tRNA aminoacylation, and gene expression. MSH3-silencing did not induce oncogenic transformation and DSBs increased 2-fold. CONCLUSIONS: MSH3-deficiency in human colon epithelial cells results in EMAST, formation of DSBs and significant changes of the proteome but lacks oncogenic transformation. Thus, MSH3-deficiency alone is unlikely to drive human colon

  9. Red Wine administration to Apolipoprotein E-deficient Mice reduces their Macrophage-derived Extracellular Matrix Atherogenic Properties

    Directory of Open Access Journals (Sweden)

    MARIELLE KAPLAN

    2004-01-01

    Full Text Available Proteoglycans (PGs from the arterial extracellular matrix (ECM contribute to the trapping of LDL and oxidized LDL (Ox-LDL in the arterial wall, a phenomenon called "lipoprotein retention". Moreover, we have shown that subsequent to their binding to the matrix, LDL and Ox-LDL are taken up by macrophages. Oxidative stress significantly increases macrophage secretion of ECM-PGs, lipoprotein binding to the ECM and the uptake of ECM-retained lipoproteins by macrophages. The aim of the present study was to determine whether red wine administration to atherosclerotic mice would affect their peritoneal macrophage-derived extracellular matrix properties, such as the glycosaminoglycan content and the ability to bind LDL. In addition, we questioned the ability of LDL bound to the mice peritoneal macrophages-derived ECM to be taken up by macrophages. Red wine administration to atherosclerotic mice did not affect the mice peritoneal macrophages-derived ECM glycosaminoglycan content but it significantly reduced the mice peritoneal macrophages-derived ECM ability to bind LDL and the subsequent uptake of ECM-retained LDL by the macrophages. The present study thus clearly demonstrated the inhibitory effect of red wine consumption by E0 mice on their peritoneal macrophage-derived extracellular matrix atherogenic properties.

  10. Ionizing radiation sensitivity of DNA polymerase lambda-deficient cells.

    NARCIS (Netherlands)

    Vermeulen, C.; Bertocci, B.; Begg, A.C.; Vens, C.

    2007-01-01

    Ionizing radiation induces a diverse spectrum of DNA lesions, including strand breaks and oxidized bases. In mammalian cells, ionizing radiation-induced lesions are targets of non-homologous end joining, homologous recombination, and base excision repair. In vitro assays show a potential involvement

  11. Splenectomy reduces packed red cell transfusion requirement in children with sickle cell disease.

    Science.gov (United States)

    Haricharan, Ramanath N; Roberts, Jared M; Morgan, Traci L; Aprahamian, Charles J; Hardin, William D; Hilliard, Lee M; Georgeson, Keith E; Barnhart, Douglas C

    2008-06-01

    The purpose of the study was to measure the effect of splenectomy on packed-cell transfusion requirement in children with sickle cell disease. Thirty-seven sickle cell children who underwent splenectomies between January 2000 and May 2006 at a children's hospital were reviewed. Data were collected 6 months preoperatively to 12 months postsplenectomy. Paired t test, analysis of variance, and multivariable regression analyses were performed. Of 37 children with median age 11 years (range, 2-18 years), 34 (21 males) had data that allowed analyses. Twenty-six had Hgb-SS, 5 had Hgb-SC, and 3 had Hgb S-Thal. Laparoscopic splenectomy was attempted in 36 and completed successfully in 34 (94% success). The number of units transfused decreased by 38% for 0 to 6 months and by 45% for 6 to 12 months postsplenectomy. Postoperatively, hematocrit levels increased and reticulocytes concurrently decreased with a reduction in transfusion clinic visits. The decrease in transfusion was not influenced by spleen weight, age, or hemoglobin type. Two children had acute chest syndrome (6%), and 1 had severe pneumonia (3%). Laparoscopic splenectomy can be successfully completed in sickle cell children. Splenectomy significantly reduces the packed red cell transfusion requirement and frequency of clinic visits, in sickle cell children for at least 12 months postoperatively.

  12. Root graviresponsiveness and columella cell structure in carotenoid-deficient seedlings of Zea mays

    Science.gov (United States)

    Moore, R.; McClelen, C. E.

    1985-01-01

    Root graviresponsiveness in normal and carotenoid-deficient mutant seedlings of Zea mays was not significantly different. Columella cells in roots of mutant seedlings were characterized by fewer, smaller, and a reduced relative volume of plastids as compared to columella cells of normal seedlings. Plastids in columella cells of mutant seedlings possessed reduced amounts of starch. Although approximately 10 per cent of the columella cells in mutant seedlings lacked starch, their plastids were located at the bottom of the cell. These results suggest that (i) carotenoids are not necessary for root gravitropism, (ii) graviresponsiveness is not necessarily proportional to the size, number, or relative volume of plastids in columella cells, and (iii) sedimentation of plastids in columella cells may not result directly from their increased density due to starch content. Plastids in columella cells of normal and mutant seedlings were associated with bands of microtubule-like structures, suggesting that these structures may be involved in 'positioning' plastids in the cell.

  13. Export of cyclic AMP by avian red cells and inhibition by prostaglandin A1

    International Nuclear Information System (INIS)

    Heasley, L.E.

    1985-01-01

    The mechanism by which PGA 1 inhibits cAMP export by avian red cells was studied, to provide details on the molecular mechanism of a prostaglandin action and on the process of cAMP export itself. The interaction of PGA 1 with pigeon red cells is a multi-step process of uptake, metabolism and secretion. [ 3 H]PGA rapidly enters red cells and is promptly metabolized (V/sub max/ ≥ 1 nmol/min/10 7 cells) to a compound (5) that remains in the aqueous layer after ethyl acetate extraction. Chromatographic analyses, amino acid content and fast atom bombardment mass spectrometry reveal that the polar metabolite is conjugated with glutathione (PGA 1 -GSH) at C-11 via a thioether bond and is largely (80%) reduced to the C-9 hydroxyl derivative

  14. Interaction of different forms of graphene with chicken embryo red blood cells

    DEFF Research Database (Denmark)

    Jaworski, S.; Hinzmann, Mateusz; Sawosz, Ewa

    2017-01-01

    , while others have indicated that graphene might become health hazards. In this study, we explore the biocompatibility of graphene-related materials with chicken embryo red blood cells (RBC). The hemolysis assay was employed to evaluate the in vitro blood compatibility of reduced graphene, graphene oxide......, and reduced graphene oxide, because these materials have recently been used for biomedical applications, including injectable graphene-related particles. This study investigated structural damage, ROS production and hemolysis of chicken embryo red blood cells. Different forms of graphene, when incubated...... with chicken embryo RBC, were harmful to cell structure and induced hemolysis....

  15. Levels of glutathione and 2,3-diphosphoglycerate in the red blood cells of Australian Aborigines.

    Science.gov (United States)

    Agar, N S

    1980-01-01

    There were no significant differences in packed cell volume (PCV) and red cell 2,3-diphosphoglycerate (2,3-DPG) levels in Australian Aborigines and Caucasians. A highly significant negative correlation was found between PCV and 2,3-DPG in both Aborigines (r = 0.251; n = 231) and Caucasians (r = 0.435; n = 227). Levels of reduced glutathione (GSH) in the red blood cells of Aborigines were significantly lower (P < 0.001) compared to those of Caucasians. There was a significant negative correlation between PCV and GSH in both the groups; (Aborigines r = -0.637, n = 115; Caucasians r = 0.388, n = 111).

  16. Theoretical and experimental study of electroporation of red blood cells using MEMS technology

    KAUST Repository

    Deng, Peigang; Yin, Guangyao; Zhang, Tong Yi; Chang, Donald C.; Lee, Yi Kuen

    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.

  17. 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.

  18. 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

  19. Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance.

    Science.gov (United States)

    Gutierrez, Dario A; Muralidhar, Sathya; Feyerabend, Thorsten B; Herzig, Stephan; Rodewald, Hans-Reimer

    2015-05-05

    Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.

    Science.gov (United States)

    Ridpath, John R; Nakamura, Ayumi; Tano, Keizo; Luke, April M; Sonoda, Eiichiro; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Gillespie, David A F; Sale, Julian E; Yamazoe, Mitsuyoshi; Bishop, Douglas K; Takata, Minoru; Takeda, Shunichi; Watanabe, Masami; Swenberg, James A; Nakamura, Jun

    2007-12-01

    Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 micromol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients.

  1. Protective role of Withaferin-a on red blood cell integrity during 7,12 ...

    African Journals Online (AJOL)

    The protective effect of Withaferin-A was assessed by measuring the status of glycoconjugates, membrane bound enzyme activity and red blood cell osmotic fragility. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 ...

  2. Inborn defects in the antioxidant systems of human red blood cells

    NARCIS (Netherlands)

    van Zwieten, Rob; Verhoeven, Arthur J.; Roos, Dirk

    2014-01-01

    Red blood cells (RBCs) contain large amounts of iron and operate in highly oxygenated tissues. As a result, these cells encounter a continuous oxidative stress. Protective mechanisms against oxidation include prevention of formation of reactive oxygen species (ROS), scavenging of various forms of

  3. Estimation of transfused red cell survival using an enzyme-linked antiglobulin test

    International Nuclear Information System (INIS)

    Kickler, T.S.; Smith, B.; Bell, W.; Drew, H.; Baldwin, M.; Ness, P.M.

    1985-01-01

    An enzyme-linked antiglobulin test (ELAT) method was developed to estimate survival of transfused red cells. This procedure is based on a principle analogous to that of the Ashby technique were antigenically distinct red cells are transfused and their survival studied. The authors compared the ELAT survival to the 51 Chromium method ( 51 Cr) in four patients. Three patients with hypoproliferative anemias showed T 1/2 by ELAT of 17.5, 18, and 17 days versus 18.5, 20, and 19 days by the 51 Cr method. A fourth patient with traumatic cardiac hemolysis had two studies performed. In this case, the ELAT showed a T 1/2 of 10 and 8.1 days while 51 Cr T 1/2 values were 11 and 10.5 days. The ELAT method for measuring red cell survival yielded data which agreed closely with the results of the 51 Cr method. Although 51 Cr is the accepted method for red cell survival, the ELAT method can be used to estimate transfused red cell survival

  4. 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.

  5. Cost comparison of methods for preparation of neonatal red cell aliquots.

    Science.gov (United States)

    Lechuga, Diana; Thompson, Christina

    2007-01-01

    The purpose of this study was to compare the preparation costs of two common methods used for neonatal red blood cell transfusion aliquots. Three months of data from a Level 2 and Level 3 neonatal intensive care unit (NICU) were used to determine the comparative cost for red cell aliquot transfusions using an eight bag aliquot/transfer system or the syringe set system. Using leuko-poor red blood cell blood collected in Adsol and containing approximately 320 ml of red blood cells and supernatant solution, the average cost of neonatal transfusion aliquots was determined using the Charter Medical syringe set and the Charter Medical eight bag aliquot/transfer system. A total of 126 red blood cell transfusion aliquots were used over the three month period. The amount transfused with each aliquot ranged from 5.0 ml - 55.0 ml with an average of 24.0 ml per aliquot. The cost per aliquot using the eight aliquot/transfer set was calculated as $36.25 and the cost per aliquot using the syringe set cost was calculated as $30.71. Additional benefits observed with the syringe set included decreased blood waste. When comparing Charter Medical multiple aliquot bag sets and the Charter Medical syringe aliquot system to provide neonatal transfusions, the use of the syringe system decreased blood waste and proved more cost effective.

  6. 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 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.

  7. Image-based model of the spectrin cytoskeleton for red blood cell simulation.

    Science.gov (United States)

    Fai, Thomas G; Leo-Macias, Alejandra; Stokes, David L; Peskin, Charles S

    2017-10-01

    We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three-dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protect against failure in the case of a red cell subjected to an applied strain. The methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.

  8. 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.

  9. [Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

    Science.gov (United States)

    Mañú Pereira, María Del Mar; Cabot, Anna; Martínez González, Ana; Sitjà Navarro, Eulalia; Cararach, Vicent; Sabrià, Josep; Boixaderas, Jordi; Teixidor, Roser; Bosch, Albert; López Vílchez, M Angeles; Martín Ibáñez, Itziar; Carrión, Teresa; Plaja, Pere; Sánchez, Mario; Vives Corrons, José Luis

    2007-06-30

    The prevalence of hemoglobinopathies and glucose-6-phosphate dehidrogenase (G6PD) deficiency in the Catalan neonatal population is increasing due to immigration. Coinheritance of more than a single RBC genetic defect is becoming more frequent and diagnostic pitfalls are also increasing. We intended to demonstrate the need to perform an early diagnosis of sickle cell disease (SCD) by means of neonatal screening, to establish the prevalence of SCD associated with alpha thalassemia and G6PD deficiency and to identify genotypes associated with sickle cell disease and G6PD deficiency. 4,020 blood samples from newborns were screened. For the screening of hemoglobinopathies the high performance liquid chromatography method was used and for G6PD deficiency the fluorescent spot test was employed. We studied the association between betaS gene and alpha thalassaemia del-3.7 Kb. SCD and G6PD deficiency genotypes were established. Prevalence of SCD in population at risk was 1/475 newborns. Prevalence of G6PD deficiency in population at risk was 1/43, and in autochthonous population was 1/527 newborns. In all the cases, sickle hemoglobin was confirmed by ARMS (amplification refractory mutation system). Association between betaS gene and alpha thalassaemia del-3.7 Kb was found in 32.2% of the samples, and an association between betaS gene and G6PD deficiency was observed in 7% of the samples. This study confirms the high prevalence of SCD and G6PD deficiency in population at risk as well as their genetic and clinical heterogeneity. The study of genotype/phenotype relationships allows a better knowledge of molecular mechanism and is useful to establish suitable criteria of diagnosis.

  10. Sphero-echinocytosis of human red blood cells caused by snake, red-back spider, bee and blue-ringed octopus venoms and its inhibition by snake sera.

    Science.gov (United States)

    Flachsenberger, W; Leigh, C M; Mirtschin, P J

    1995-06-01

    It was found that bee (Apis mellifera) venom, red-back spider (Latrodectus mactans) venom, blue-ringed octopus (Hapalochlaena maculosa) venom, ten different snake venoms, phospholipase A2 and four snake toxins caused sphero-echinocytosis of human red blood cells at 200 ng/ml. Most venoms and toxins lost the ability to deform human red blood cells when their components of less than mol. wt 10,000 were applied. In a number of cases the sphero-echinocytotic effect was also inhibited by blood sera of Notechis scutatus and Pseudonaja textilis.

  11. Deformation of Two-Dimensional Nonuniform-Membrane Red Blood Cells Simulated by a Lattice Boltzmann Model

    International Nuclear Information System (INIS)

    Hua-Bing, Li; Li, Jin; Bing, Qiu

    2008-01-01

    To study two-dimensional red blood cells deforming in a shear Bow 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. (fundamental areas of phenomenology(including applications))

  12. Red wine consumption improves in vitro migration of endothelial progenitor cells in young, healthy individuals.

    Science.gov (United States)

    Hamed, Saher; Alshiek, Jonia; Aharon, Anat; Brenner, Benjamin; Roguin, Ariel

    2010-07-01

    Endothelial progenitor cells (EPCs) contribute to the maintenance of vascular endothelial function. The moderate consumption of red wine provides cardiovascular protection. We investigated the underlying molecular mechanism of EPC migration in young, healthy individuals who drank red wine. Fourteen healthy volunteers consumed 250 mL red wine daily for 21 consecutive days. Vascular endothelial function, plasma stromal cell-derived factor 1alpha (SDF1alpha) concentrations, and the number, migration, and nitric oxide production of EPCs were determined before and after the daily consumption of red wine. EPCs were glucose stressed to study the effect of red wine on EPC migration, proliferation, and senescence and to study the expressions of CXC chemokine receptor 4 (CXCR4) and members of the Pi3K/Akt/eNOS (phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase) signaling pathway by Western blotting. Daily red wine consumption for 21 consecutive days significantly enhanced vascular endothelial function. Although plasma SDF1alpha concentrations were unchanged, EPC count and migration were significantly increased after this 21-d consumption period. Red wine increased the migration, proliferation, CXCR4 expression, and activity of the Pi3K/Akt/eNOS signaling pathway and decreased the extent of apoptosis in glucose-stressed EPCs. The results of the present study indicate that red wine exerts its effect through the up-regulation of CXCR4 expression and activation of the SDF1alpha/CXCR4/Pi3K/Akt/eNOS signaling pathway, which results in increased EPC migration and proliferation and decreased extent of apoptosis. Our findings suggest that these effects could be linked to the mechanism of cardiovascular protection that is associated with the regular consumption of red wine.

  13. Uptake and metabolism of structured triglyceride by Caco-2 cells: reversal of essential fatty acid deficiency.

    Science.gov (United States)

    Spalinger, J H; Seidman, E G; Lepage, G; Ménard, D; Gavino, V; Levy, E

    1998-10-01

    Structured lipids have been proposed as efficient vehicles for the supplementation of essential fatty acids (EFA) to patients with malabsorption. We investigated how a novel structured triglyceride (STG), containing purely octanoic acid in the sn-1/sn-3 and [14C]linoleic acid in the sn-2 positions, was incorporated into different lipid classes in Caco-2 cells. We also evaluated the contribution of gastric lipase in the uptake and metabolism of [14C]linoleic acid from the STG. We furthermore determined the potential of the STG to correct EFA deficiency induced in Caco-2 cells. The absorption of STG by Caco-2 cells was significantly greater compared with that of triolein. The addition of human gastric lipase significantly enhanced cellular uptake of the labeled substrate, reflecting the stereoselectivity of gastric lipase to hydrolyze medium chain FA. Analysis of the intracellular lipids synthesized revealed a predominance of phospholipids-monoglycerides. Most of the radioactivity in the lipoproteins isolated from Caco-2 cells was recovered in TG-rich lipoproteins (45%) and to a lesser extent in the high-density lipoprotein (36%) and low-density lipoprotein (17%) fractions. The administration of STG to Caco-2 cells rendered EFA deficient produced a marked increase of the cellular level of linoleic and arachidonic acids. This resulted in a lower ratio of 20:3(n-9) to 20:4(n-6), reflecting the correction of EFA deficiency in Caco-2 cells. Our data demonstrate that STG, in the presence of gastric lipase, have beneficial effects on lipid incorporation, lipoprotein production, and EFA status, utilizing Caco-2 cells as a model of EFA deficiency.

  14. Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

    Directory of Open Access Journals (Sweden)

    Jose Luis Ramirez-GarciaLuna

    Full Text Available In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1 mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2 re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3 the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.

  15. Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

    Science.gov (United States)

    Ramirez-GarciaLuna, Jose Luis; Chan, Daniel; Samberg, Robert; Abou-Rjeili, Mira; Wong, Timothy H; Li, Ailian; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Henderson, Janet E; Martineau, Paul A

    2017-01-01

    In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.

  16. Distorted secretory granule composition in mast cells with multiple protease deficiency.

    Science.gov (United States)

    Grujic, Mirjana; Calounova, Gabriela; Eriksson, Inger; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Tchougounova, Elena; Kjellén, Lena; Pejler, Gunnar

    2013-10-01

    Mast cells are characterized by an abundance of secretory granules densely packed with inflammatory mediators such as bioactive amines, cytokines, serglycin proteoglycans with negatively charged glycosaminoglycan side chains of either heparin or chondroitin sulfate type, and large amounts of positively charged proteases. Despite the large biological impact of mast cell granules and their contents on various pathologies, the mechanisms that regulate granule composition are incompletely understood. In this study, we hypothesized that granule composition is dependent on a dynamic electrostatic interrelationship between different granule compounds. As a tool to evaluate this possibility, we generated mice in which mast cells are multideficient in a panel of positively charged proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast cells from these mice additionally lack mouse mast cell protease-5 protein. Mast cells from mice deficient in individual proteases showed normal morphology. In contrast, mast cells with combined protease deficiency displayed a profound distortion of granule integrity, as seen both by conventional morphological criteria and by transmission electron microscopy. An assessment of granule content revealed that the distorted granule integrity in multiprotease-deficient mast cells was associated with a profound reduction of highly negatively charged heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken together with previous findings showing that the storage of basic proteases conversely is regulated by anionic proteoglycans, these data suggest that secretory granule composition in mast cells is dependent on a dynamic interrelationship between granule compounds of opposite electrical charge.

  17. Inability to induce tympanic squamous metaplasia using organochlorine compounds in vitamin A-deficient red-eared sliders (Trachemys scripta elegans).

    Science.gov (United States)

    Kroenlein, Karl R; Sleeman, Jonathan M; Holladay, Steven D; Joyner, Priscilla H; Brown, Justin D; Griffin, Mark; Saunders, Geoffrey; Smith, Stephen A

    2008-07-01

    Previously, we reported that wild eastern box turtles (Terrapene carolina carolina) with aural abscesses contained higher body burdens of organochlorine (OC) compounds than those without the lesion. This lesion in captive chelonians is associated with turtles that are fed diets deficient in vitamin A. To examine the pathophysiology of this lesion and evaluate the relationship between OC burdens and vitamin A metabolism, we maintained red-eared sliders (Trachemys scripta elegans) under different conditions of OC exposure and dietary vitamin A concentrations from August 2005 to February 2006. Dietary vitamin A concentration (0 or 5 international units/g in the diet) and OC exposure (no OC compound or the mixture of 2 mg/kg chlordane, 0.25 mg/kg aroclor, and 1 mg/kg lindane) did not affect histologic score based on degree of squamous metaplasia of the tympanic epithelium or levels of plasma or liver vitamin A among the study groups. The results of this study suggest that 6 mo of exposure to the selected OC compounds, or similar duration of reduced dietary vitamin A concentrations do not influence the formation of squamous metaplasia and aural abscesses in red-eared sliders. Further studies are required to determine whether the duration of the experiment was insufficient, the OC compounds selected were inappropriate, the dosing was incorrect, and whether there are other unknown mechanisms causing the reported association between OC exposure and aural abscesses seen in eastern box turtles.

  18. Cross-stream distribution of red blood cells in sickle-cell disease

    Science.gov (United States)

    Zhang, Xiao; Lam, Wilbur; Graham, Michael

    2017-11-01

    Experiments revealed that in blood flow, red blood cells (RBCs) tend to migrate away from the vessel walls, leaving a cell-free layer near the walls, while leukocytes and platelets tend to marginate towards the vessel walls. This segregation behavior of different cellular components in blood flow can be driven by their differences in stiffness and shape. An alteration of this segregation behavior may explain endothelial dysfunction and pain crisis associated with sickle-cell disease (SCD). It is hypothesized that the sickle RBCs, which are considerably stiffer than the healthy RBCs, may marginate towards the vessel walls and exert repeated damage to the endothelial cells. Direct simulations are performed to study the flowing suspensions of deformable biconcave discoids and stiff sickles representing healthy and sickle cells, respectively. It is observed that the sickles exhibit a strong margination towards the walls. The biconcave discoids in flowing suspensions undergo a so-called tank-treading motion, while the sickles behave as rigid bodies and undergo a tumbling motion. The margination behavior and tumbling motion of the sickles may help substantiate the aforementioned hypothesis of the mechanism for the SCD complications and shed some light on the design of novel therapies.

  19. Measurement of the viability of stored red cells by the single-isotope technique using 51Cr. Analysis of validity

    International Nuclear Information System (INIS)

    Beutler, E.; West, C.

    1984-01-01

    A single-isotope 51 Cr method often is used to evaluate the viability of stored red cells. In this technique, the red cell mass is measured by back-extrapolation to time zero (t0) of the radioactivity of the blood between 5 and 20 minutes after infusion of the sample. If there is early destruction of stored cells, this method provides an overestimate of the red cell mass and, hence, of the viability of the stored cells. Freshly drawn red cells from normal donors were labeled with /sup 99m/Tc, and cells from the same donor which had been stored in citrate-phosphate-dextrose-adenine-one (CPDA-1) for periods ranging from 7 to 49 days were labeled with 51 Cr. A comparison of the ''true red cell mass'' as determined with /sup 99m/Tc with the back-extrapolated red cell mass from stored 51 Cr-labeled cells has made it possible to define the magnitude of error introduced by early loss of red cells. The overestimation of red cell mass and viability was diminished if only the 51 Cr radioactivity between 5 and 15 minutes after infusion was used in back-extrapolating to t0. The degree of overestimation of red cell mass was greatest when the red cell viability had declined to very low levels. However, in the entire range of 10 to 80 percent viability, the overestimate of viability was usually less than 4 percent. The overestimate of viability proved to be quite similar for all samples and may be taken into account when using the single-isotope technique for measurement of red cell viability

  20. Mitochondrial modification and respiratory deficiency in the yeast cell caused by cadmium poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Lindegren, C C; Lindegren, G

    1973-01-01

    Cells of Fleischmann bakers' yeast were grown in standard nutrient broth and in broth to which cobalt, or cadmium, or thallium, had been added. The cells were fixed by glutaraldehyde-permanganate and sectioned. Electron microscopy showed that (a) the endoplasmic reticulum was fixed well in cells grown in cobalt or cadmium, but the endoplasmic reticulum was not fixed in cells grown in normal or thallium broth; (b) the cristate mitochondria were normal in all cells except those grown in cadmium. No cristae were visible in the cristate mitochondria of cells grown in cadmium broth; (c) a large fraction of the cells recovered from cadmium broth were respiratory-deficient; (d) thallic oxide was present in the cristate mitochondria of cells recovered from thallium broth. 13 references, 3 figures.

  1. Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

    Science.gov (United States)

    2014-03-01

    repair defects asso- ciated with downstream mediators of the HR reaction (e.g., XRCC2, BRCA2, or PALB2) (Bouwman et al., 2010; Bowman- Colin et al., 2013...and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol. 17, 688–695. Bowman- Colin , C., Xia, B., Bunting, S., Klijn, C., Drost, R., Bouwman, P., Fine...chromosomes. It is thus surprising that cells use ‘quick and dirty ’ repair by NHEJ rather than the slower, more accurate repair by homologous recombination

  2. Prevalence of glucose-6-phosphate dehydrogenase deficiency and sickle cell trait among blood donors in Riyadh

    Directory of Open Access Journals (Sweden)

    Alabdulaali Mohammed

    2010-01-01

    Full Text Available Background and Aims: Blood donation from glucose-6-phosphate dehydrogenase (G6PD-deficient and sickle cell trait (SCT donors might alter the quality of the donated blood during processing, storage or in the recipient′s circulatory system. The aim of this study was to determine the prevalence of G6PD deficiency and SCT among blood donors coming to King Khalid University Hospital (KKUH in Riyadh. It was also reviewed the benefits and risks of transfusing blood from these blood donors. Materials and Methods: This cross-sectional study was conducted on 1150 blood samples obtained from blood donors that presented to KKUH blood bank during the period April 2006 to May 2006. All samples were tested for Hb-S by solubility test, alkaline gel electrophoresis; and for G6PD deficiency, by fluorescent spot test. Results: Out of the 1150 donors, 23 (2% were diagnosed for SCT, 9 (0.78% for G6PD deficiency and 4 (0.35% for both conditions. Our prevalence of SCT and G6PD deficiency is higher than that of the general population of Riyadh. Conclusion: We recommend to screen all units for G6PD deficiency and sickle cell trait and to defer donations from donors with either of these conditions, unless if needed for special blood group compatibility, platelet apheresis or if these are likely to affect the blood bank inventory. If such blood is to be used, special precautions need to be undertaken to avoid complications in high-risk recipients.

  3. Aplasia versus pancytopenia, including the pure red cell variant

    African Journals Online (AJOL)

    to extend evaluation to the bone marrow and plasma while supplementary imaging ... B lood. Pluripotential stem cell. Early acting molecules, primarily interleukins .... options towards early immunohaematopoietic stem cell allogeneic transplantation. ... Chronic leukaemia, leukaemia, lymphomas; large granular lymphocytic ...

  4. 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)

  5. Getting into the flow: Red cells go on a roll, two-component vesicles swing

    Science.gov (United States)

    Viallat, Annie; Dupire, Jules; Khelloufi, Kamel; Al Halifa, Al Hair; Adhesion and Inflammation Team

    2013-11-01

    Red blood cells are soft capsules. Under shear flow, their two known motions were ``tumbling'' and ``swinging-tank treading,'' depending on cell mechanics and flow conditions. We reveal new wobbling regimes, among which the ``rolling'' regime, where red cells move as wheels on a road. We show, by coupling two video-microscopy approaches providing multi-directional cell pictures that the orientation of cells flipping into the flow is determined by the shear rate. Rolling permits to avoid energetically costly cellular deformations and is a true signature of the cytoskeleton elasticity. We highlight two transient dynamics: an intermittent regime during the ``tank-treading-to-flipping'' transition and a Frisbee-like ``spinning'' regime during the ``rolling-to-tank-treading'' transition. We find that the biconcave red cell shape is very stable under moderate shear stresses, and we interpret this result in terms of shape memory and elastic buckling. Finally, we generate lipid vesicles with a shape memory by using two lipids with different bending rigidities. These vesicles swing in shear flow similarly to red blood cells but their non-axisymmetric stress-free shape changes the periodicity of the motion and induces specific features.

  6. Long-term culture and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized mesenchymal cells.

    Science.gov (United States)

    Garba, Abubakar; Acar, Delphine D; Roukaerts, Inge D M; Desmarets, Lowiese M B; Devriendt, Bert; Nauwynck, Hans J

    2017-09-01

    Mesenchymal cells are multipotent stromal cells with self-renewal, differentiation and immunomodulatory capabilities. We aimed to develop a co-culture model for differentiating hematopoietic cells on top of immortalized mesenchymal cells for studying interactions between hematopoietic and mesenchymal cells, useful for adequately exploring the therapeutic potential of mesenchymal cells. In this study, we investigated the survival, proliferation and differentiation of porcine red bone marrow hematopoietic cells co-cultured with immortalized porcine bone marrow mesenchymal cells for a period of five weeks. Directly after collection, primary porcine bone marrow mesenchymal cells adhered firmly to the bottom of the culture plates and showed a fibroblast-like appearance, one week after isolation. Upon immortalization, porcine bone marrow mesenchymal cells were continuously proliferating. They were positive for simian virus 40 (SV40) large T antigen and the mesenchymal cell markers CD44 and CD55. Isolated red bone marrow cells were added to these immortalized mesenchymal cells. Five weeks post-seeding, 92±6% of the red bone marrow hematopoietic cells were still alive and their number increased 3-fold during five weekly subpassages on top of the immortalized mesenchymal cells. The red bone marrow hematopoietic cells were originally small and round; later, the cells increased in size. Some of them became elongated, while others remained round. Tiny dendrites appeared attaching hematopoietic cells to the underlying immortalized mesenchymal cells. Furthermore, weekly differential-quick staining of the cells indicated the presence of monoblasts, monocytes, macrophages and lymphocytes in the co-cultures. At three weeks of co-culture, flow cytometry analysis showed an increased surface expression of CD172a, CD14, CD163, CD169, CD4 and CD8 up to 37±0.8%, 40±8%, 41±4%, 23±3% and 19±5% of the hematopoietic cells, respectively. In conclusion, continuous mesenchymal cell

  7. Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice.

    Science.gov (United States)

    Zheng, Lingjie; Sharma, Rahul; Kung, John T; Deshmukh, Umesh S; Jarjour, Wael N; Fu, Shu Man; Ju, Shyr-Te

    2008-04-01

    We hypothesize that regulatory T-cell (Treg)-deficient strains have an altered TCR repertoire in part due to the expansion of autoimmune repertoire by self-antigen. We compared the Vbeta family expression profile between B6 and Treg-lacking B6.Cg-Foxp3(sf)(/Y) (B6.sf) mice using fluorescent anti-Vbeta mAbs and observed no changes. However, while the spectratypes of 20 Vbeta families among B6 mice were highly similar, the Vbeta family spectratypes of B6.sf mice were remarkably different from B6 mice and from each other. Significant spectratype changes in many Vbeta families were also observed in Treg-deficient IL-2 knockout (KO) and IL-2Ralpha KO mice. Such changes were not observed with anti-CD3 mAb-treated B6 mice or B6 CD4+CD25- T cells. TCR transgenic (OT-II.sf) mice displayed dramatic reduction of clonotypic TCR with concomitant increase in T cells bearing non-transgenic Vbeta and Valpha families, including T cells with dual receptors expressing reduced levels of transgenic Valpha and endogenous Valpha. Collectively, the data demonstrate that Treg deficiency allows polyclonal expansion of T cells in a stochastic manner, resulting in widespread changes in the TCR repertoire.

  8. HOIP Deficiency Causes Embryonic Lethality by Aberrant TNFR1-Mediated Endothelial Cell Death

    Directory of Open Access Journals (Sweden)

    Nieves Peltzer

    2014-10-01

    Full Text Available Summary: Linear ubiquitination is crucial for innate and adaptive immunity. The linear ubiquitin chain assembly complex (LUBAC, consisting of HOIL-1, HOIP, and SHARPIN, is the only known ubiquitin ligase that generates linear ubiquitin linkages. HOIP is the catalytically active LUBAC component. Here, we show that both constitutive and Tie2-Cre-driven HOIP deletion lead to aberrant endothelial cell death, resulting in defective vascularization and embryonic lethality at midgestation. Ablation of tumor necrosis factor receptor 1 (TNFR1 prevents cell death, vascularization defects, and death at midgestation. HOIP-deficient cells are more sensitive to death induction by both tumor necrosis factor (TNF and lymphotoxin-α (LT-α, and aberrant complex-II formation is responsible for sensitization to TNFR1-mediated cell death in the absence of HOIP. Finally, we show that HOIP’s catalytic activity is necessary for preventing TNF-induced cell death. Hence, LUBAC and its linear-ubiquitin-forming activity are required for maintaining vascular integrity during embryogenesis by preventing TNFR1-mediated endothelial cell death. : HOIP is the main catalytic subunit of the linear ubiquitin chain assembly complex (LUBAC, a crucial regulator of TNF and other immune signaling pathways. Peltzer et al. find that HOIP deficiency results in embryonic lethality at midgestation due to endothelial cell death mediated by TNFR1. Aberrant formation of a TNF-mediated cell-death-inducing complex in HOIP-deficient (but not -proficient cells underlies the phenotype, with the catalytic activity of HOIP required for the control of cell death in response to TNF.

  9. Local membrane deformations activate Ca2+-dependent K+ and anionic currents in intact human red blood cells

    DEFF Research Database (Denmark)

    Dyrda, Agnieszka; Cytlak, Urszula; Ciuraszkiewicz, Anna

    2010-01-01

    -activated transient PCa observed here under local membrane deformation is a likely contributor to the Ca(2+)-mediated effects observed during the normal aging process of red blood cells, and to the increased Ca(2+) content of red cells in certain hereditary anemias such as thalassemia and sickle cell anemia....

  10. Detecting Newcastle disease virus in combination of RT-PCR with red blood cell absorption

    Directory of Open Access Journals (Sweden)

    Liu Chengqian

    2011-05-01

    Full Text Available Abstract Reverse transcription-polymerase chain reaction (RT-PCR has limited sensitivity when treating complicated samples, such as feces, waste-water in farms, and nucleic acids, protein rich tissue samples, all the factors may interfere with the sensitivity of PCR test or generate false results. In this study, we developed a sensitive RT-PCR, combination of red blood cell adsorption, for detecting Newcastle disease virus (NDV. One pair of primers which was highly homologous to three NDV pathotypes was designed according to the consensus nucleocapsid protein (NP gene sequence. To eliminate the interfere of microbes and toxic substances, we concentrated and purified NDV from varied samples utilizing the ability of NDV binding red blood cells (RBCs. The RT-PCR coupled with red blood cell adsorption was much more sensitive in comparison with regular RT-PCR. The approach could also be used to detect other viruses with the property of hemagglutination, such as influenza viruses.

  11. Geometrical Aspects During Formation of Compact Aggregates of Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Cardoso A.V.

    2002-01-01

    Full Text Available In the past forty years considerable progress has been achieved on the knowledge of human blood as a non-Newtonian shear-thinning suspension, whose initial state, that is at rest (stasis or at very low shear rates, has a gel-like internal structure which is destroyed as shear stress increases. The main goal of this communication is to describe the role of geometrical aspects during RBC (red blood cell aggregate formation, growth and compaction on naturally aggregate (porcine blood and non-aggregate (bovine blood samples. We consider how these aspects coupled with tension equilibrium are decisive to transform red cell linear roleaux to three-dimensional aggregates or clusters. Geometrical aspects are also crucial on the compaction of red blood cell aggregates. These densely packed aggregates could precipitate out of blood- either as dangerous deposits on arterial walls, or as clots which travel in suspension until they block some crucial capillary.

  12. Membrane transport of anandamide through resealed human red blood cell membranes

    DEFF Research Database (Denmark)

    Bojesen, I.N.; Hansen, Harald S.

    2005-01-01

    The use of resealed red blood cell membranes (ghosts) allows the study of the transport of a compound in a nonmetabolizing system with a biological membrane. Transmembrane movements of anandamide (N-arachidonoylethanolamine, arachidonoylethanolamide) have been studied by exchange efflux experiments...... at 0°C and pH 7.3 with albumin-free and albumin-filled human red blood cell ghosts. The efflux kinetics is biexponential and is analyzed in terms of compartment models. The distribution of anandamide on the membrane inner to outer leaflet pools is determined to be 0.275 ± 0.023, and the rate constant...... of unidirectional flux from inside to outside is 0.361 ± 0.023 s. The rate constant of unidirectional flux from the membrane to BSA in the medium ([BSA]) increases with the square root of [BSA] in accordance with the theory of an unstirred layer around ghosts. Anandamide passed through the red blood cell membrane...

  13. Computer Simulation Study of Collective Phenomena in Dense Suspensions of Red Blood Cells under Shear

    CERN Document Server

    Krüger, Timm

    2012-01-01

    The rheology of dense red blood cell suspensions is investigated via computer simulations based on the lattice Boltzmann, the immersed boundary, and the finite element methods. The red blood cells are treated as extended and deformable particles immersed in the ambient fluid. In the first part of the work, the numerical model and strategies for stress evaluation are discussed. In the second part, the behavior of the suspensions in simple shear flow is studied for different volume fractions, particle deformabilities, and shear rates. Shear thinning behavior is recovered. The existence of a shear-induced transition from a tumbling to a tank-treading motion is demonstrated. The transition can be parameterized by a single quantity, namely the effective capillary number. It is the ratio of the suspension stress and the characteristic particle membrane stress. At the transition point, a strong increase in the orientational order of the red blood cells and a significant decrease of the particle diffusivity are obser...

  14. High-speed video capillaroscopy method for imaging and evaluation of moving red blood cells

    Science.gov (United States)

    Gurov, Igor; Volkov, Mikhail; Margaryants, Nikita; Pimenov, Aleksei; Potemkin, Andrey

    2018-05-01

    The video capillaroscopy system with high image recording rate to resolve moving red blood cells with velocity up to 5 mm/s into a capillary is considered. Proposed procedures of the recorded video sequence processing allow evaluating spatial capillary area, capillary diameter and central line with high accuracy and reliability independently on properties of individual capillary. Two-dimensional inter frame procedure is applied to find lateral shift of neighbor images in the blood flow area with moving red blood cells and to measure directly the blood flow velocity along a capillary central line. The developed method opens new opportunities for biomedical diagnostics, particularly, due to long-time continuous monitoring of red blood cells velocity into capillary. Spatio-temporal representation of capillary blood flow is considered. Experimental results of direct measurement of blood flow velocity into separate capillary as well as capillary net are presented and discussed.

  15. Screening hypochromism (sieve effect) in red blood cells: a quantitative analysis.

    Science.gov (United States)

    Razi Naqvi, K

    2014-04-01

    Multiwavelength UV-visible spectroscopy, Kramers-Kronig analysis, and several other experimental and theoretical tools have been applied over the last several decades to fathom absorption and scattering of light by suspensions of micron-sized pigmented particles, including red blood cells, but a satisfactory quantitative analysis of the difference between the absorption spectra of suspension of intact and lysed red blood cells is still lacking. It is stressed that such a comparison is meaningful only if the pertinent spectra are free from, or have been corrected for, scattering losses, and it is shown that Duysens' theory can, whereas that of Vekshin cannot, account satisfactorily for the observed hypochromism of suspensions of red blood cells.

  16. Hyperkalemia caused by rapid red cell transfusion and the potassium absorption filter

    Directory of Open Access Journals (Sweden)

    Yasuhiko Imashuku

    2017-01-01

    Full Text Available We report a case of transient hyperkalemia during hysterectomy after cesarean section, due to preoperatively undiagnosed placenta accreta that caused unforeseen massive hemorrhage and required rapid red cell transfusion. Hyperkalemia-induced by rapid red cell transfusion is a well-known severe complication of transfusion; however, in patients with sudden massive hemorrhage, rapid red cell transfusion is necessary to save their life. In such cases, it is extremely important to monitor serum potassium levels. For an emergency situation, a system should be developed to ensure sufficient preparation for immediate transfusion and laboratory tests. Furthermore, sufficient stock of preparations to treat hyperkalemia, such as calcium preparations, diuretics, glucose, and insulin is required. Moreover, a transfusion filter that absorbs potassium has been developed and is now available for clinical use in Japan. The filter is easy to use and beneficial, and should be prepared when it is available.

  17. Hyperkalemia caused by rapid red cell transfusion and the potassium absorption filter

    Science.gov (United States)

    Imashuku, Yasuhiko; Kitagawa, Hirotoshi; Mizuno, Takayoshi; Fukushima, Yutaka

    2017-01-01

    We report a case of transient hyperkalemia during hysterectomy after cesarean section, due to preoperatively undiagnosed placenta accreta that caused unforeseen massive hemorrhage and required rapid red cell transfusion. Hyperkalemia-induced by rapid red cell transfusion is a well-known severe complication of transfusion; however, in patients with sudden massive hemorrhage, rapid red cell transfusion is necessary to save their life. In such cases, it is extremely important to monitor serum potassium levels. For an emergency situation, a system should be developed to ensure sufficient preparation for immediate transfusion and laboratory tests. Furthermore, sufficient stock of preparations to treat hyperkalemia, such as calcium preparations, diuretics, glucose, and insulin is required. Moreover, a transfusion filter that absorbs potassium has been developed and is now available for clinical use in Japan. The filter is easy to use and beneficial, and should be prepared when it is available. PMID:28217070

  18. Radionuclide assay of membrane Na+, K+-ATPase activity of peserved red blood cells

    International Nuclear Information System (INIS)

    Trusov, V.V.; Zelenin, A.A.; Marizin, S.A.

    1986-01-01

    The radionuclide tests were used to investigate the influence of varying blood preservatives on erythrocylic membrane Na + , K + -ATPase activity in samples of whole blood and packed red blood cells from normal donors prepared by standard methods. The tests were performed before and after seven days of preservation under standard conditions. It was found that blood preservations lowered membrane Na + , K + -ATPase activity: its minimum reduction was recorded with citroglucopnosphate, while glugicir induced a significant drop in Na + , K + -ATPase activity of preserved red blood cells regardless of the type of the blood transfusion solution. The assay of membrane Na + , K + -ATPase activity of preserved red blood cells with the use of 86 Rb could be recommended as an evaluation test for preserved blood and its components

  19. Method for extending the useful shelf-life of refrigerated red blood cells by flushing with inert gas

    Science.gov (United States)

    Bitensky, Mark W.; Yoshida, Tatsuro

    1997-01-01

    Method using oxygen removal for extending the useful shelf-life of refrigerated red blood cells. A cost-effective, 4.degree. C. storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. Preservation of adenosine triphosphate levels and reduction in hemolysis and in membrane vesicle production of red blood cells stored at 4.degree. C. for prolonged periods of time is achieved by removing oxygen therefrom at the time of storage; in particular, by flushing with an inert gas. Adenosine triphosphate levels of the stored red blood cells are boosted in some samples by addition of ammonium phosphate.

  20. Importance of methodological standardization for the ektacytometric measures of red blood cell deformability in sickle cell anemia

    NARCIS (Netherlands)

    Renoux, Céline; Parrow, Nermi; Faes, Camille; Joly, Philippe; Hardeman, Max; Tisdale, John; Levine, Mark; Garnier, Nathalie; Bertrand, Yves; Kebaili, Kamila; Cuzzubbo, Daniela; Cannas, Giovanna; Martin, Cyril; Connes, Philippe

    2016-01-01

    Red blood cell (RBC) deformability is severely decreased in patients with sickle cell anemia (SCA), which plays a role in the pathophysiology of the disease. However, investigation of RBC deformability from SCA patients demands careful methodological considerations. We assessed RBC deformability by

  1. Evaluation of the effectiveness of packed red blood cell irradiation by a linear accelerator.

    Science.gov (United States)

    Olivo, Ricardo Aparecido; da Silva, Marcus Vinícius; Garcia, Fernanda Bernadelli; Soares, Sheila; Rodrigues Junior, Virmondes; Moraes-Souza, Helio

    2015-01-01

    Irradiation of blood components with ionizing radiation generated by a specific device is recommended to prevent transfusion-associated graft-versus-host disease. However, a linear accelerator can also be used in the absence of such a device, which is the case of the blood bank facility studied herein. In order to evaluate the quality of the irradiated packed red blood cells, this study aimed to determine whether the procedure currently employed in the facility is effective in inhibiting the proliferation of T lymphocytes without damaging blood components. The proliferation of T lymphocytes, plasma potassium levels, and the degree of hemolysis were evaluated and compared to blood bags that received no irradiation. Packed red blood cell bags were irradiated at a dose of 25Gy in a linear accelerator. For this purpose, a container was designed to hold the bags and to ensure even distribution of irradiation as evaluated by computed tomography and dose-volume histogram. Irradiation was observed to inhibit the proliferation of lymphocytes. The percentage of hemolysis in irradiated bags was slightly higher than in non-irradiated bags (p-value >0.05), but it was always less than 0.4% of the red cell mass. Although potassium increased in both groups, it was more pronounced in irradiated red blood cells, especially after seven days of storage, with a linear increase over storage time. The findings showed that, at an appropriate dosage and under validated conditions, the irradiation of packed red blood cells in a linear accelerator is effective, inhibiting lymphocyte proliferation but without compromising the viability of the red cells. Copyright © 2015 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  2. Effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat

    International Nuclear Information System (INIS)

    Barton, R.W.

    1985-01-01

    Inherited deficiency of the enzyme adenosine deaminase (ADA) has been found in a significant proportion of patients with severe combined immunodeficiency disease and inherited defect generally characterized by a deficiency of both B and T cells. Two questions are central to understanding the pathophysiology of this disease: (1) at what stage or stages in lymphocyte development are the effects of the enzyme deficiency manifested; (2) what are the biochemical mechanisms responsible for the selective pathogenicity of the lymphoid system. We have examined the stage or stages of rat T-cell development in vivo which are affected by an induced adenosine deaminase deficiency using the ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2'-deoxycoformycin (DCF). In normal rats given daily administration of an ADA inhibitor, cortical thymocytes were markedly depleted; peripheral lymphocytes and pluripotent hemopoietic stem cells (CFU-S) all were relatively unaffected. Since a deficiency of ADA affects lymphocyte development, the regeneration of cortical and medullary thymocytes and their precursors after sublethal irradiation was used as a model of lymphoid development. By Day 5 after irradiation the thymus was reduced to 0.10-0.5% of its normal size; whereas at Days 9 and 14 the thymus was 20-40% and 60-80% regenerated, respectively. When irradiated rats were given daily parenteral injections of the ADA inhibitor plus adenosine or deoxyadenosine, thymus regeneration at Days 9 and 14 was markedly inhibited, whereas the regeneration of thymocyte precursors was essentially unaffected. Thymus regeneration was at least 40-fold lower than in rats given adenosine or deoxyadenosine alone. Virtually identical results were obtained with both ADA inhibitors, EHNA and DCF

  3. Concise review: stem cell-based approaches to red blood cell production for transfusion.

    Science.gov (United States)

    Shah, Siddharth; Huang, Xiaosong; Cheng, Linzhao

    2014-03-01

    Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply. Even in developed countries where the supply is currently adequate, projected demographics predict an insufficient supply as early as 2050. The blood supply is also strained during occasional widespread disasters and crises. Transfusion of blood components such as red blood cells (RBCs), platelets, or neutrophils is increasingly used from the same blood unit for multiple purposes and to reduce alloimmune responses. Even for RBCs and platelets lacking nuclei and many antigenic cell-surface molecules, alloimmunity could occur, especially in patients with chronic transfusion requirements. Once alloimmunization occurs, such patients require RBCs from donors with a different blood group antigen combination, making it a challenge to find donors after every successive episode of alloimmunization. Alternative blood substitutes such as synthetic oxygen carriers have so far proven unsuccessful. In this review, we focus on current research and technologies that permit RBC production ex vivo from hematopoietic stem cells, pluripotent stem cells, and immortalized erythroid precursors.

  4. Induced Pluripotent Stem Cell-Derived Red Blood Cells and Platelet Concentrates: From Bench to Bedside.

    Science.gov (United States)

    Focosi, Daniele; Amabile, Giovanni

    2017-12-27

    Red blood cells and platelets are anucleate blood components indispensable for oxygen delivery and hemostasis, respectively. Derivation of these blood elements from induced pluripotent stem (iPS) cells has the potential to develop blood donor-independent and genetic manipulation-prone products to complement or replace current transfusion banking, also minimizing the risk of alloimmunization. While the production of erythrocytes from iPS cells has challenges to overcome, such as differentiation into adult-type phenotype that functions properly after transfusion, platelet products are qualitatively and quantitatively approaching a clinically-applicable level owing to advances in expandable megakaryocyte (MK) lines, platelet-producing bioreactors, and novel reagents. Guidelines that assure the quality of iPS cells-derived blood products for clinical application represent a novel challenge for regulatory agencies. Considering the minimal risk of tumorigenicity and the expected significant demand of such products, ex vivo production of iPS-derived blood components can pave the way for iPS translation into the clinic.

  5. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

    Directory of Open Access Journals (Sweden)

    Michael P. Pender

    2012-01-01

    Full Text Available CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1 CD8+ T-cell deficiency, (2 primary EBV infection, (3 decreased CD8+ T-cell control of EBV, (4 increased EBV load and increased anti-EBV antibodies, (5 EBV infection in the target organ, (6 clonal expansion of EBV-infected autoreactive B cells in the target organ, (7 infiltration of autoreactive T cells into the target organ, and (8 development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

  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

    encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants......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...

  7. Simultaneous determination of size and refractive index of red blood cells by light scattering measurements

    International Nuclear Information System (INIS)

    Ghosh, N.; Buddhiwant, P.; Uppal, A.; Majumder, S.K.; Patel, H.S.; Gupta, P.K.

    2006-01-01

    We present a fast and accurate approach for simultaneous determination of both the mean diameter and refractive index of a collection of red blood cells (RBCs). The approach uses the peak frequency of the power spectrum and the corresponding phase angle obtained by performing Fourier transform on the measured angular distribution of scattered light to determine these parameters. Results on the measurement of two important clinical parameters, the mean cell volume and mean cell hemoglobin concentration of a collection of RBCs, are presented

  8. Improved modification for in vitro labeling of red blood cells with Technetium-99m

    International Nuclear Information System (INIS)

    Gerson, B.; Ballinger, J.R.; Gulenchyn, K.Y.

    1988-01-01

    The authors have tested a modification of Brookhaven method for in vitro labeling of red blood cells (RBCs) with technetium-99m by adding an initial centrifugation step and performing the labeling on packed RBCs. This results in reproducible, high labeling efficiencies (99.3% +/- 0.4%, n = 50) after 15 min of incubation. The use of packed RBCs also results in a higher concentration of labeled RBCs (smaller bolus for injection) and less radiation exposure to the technologist. This technique has proved useful for radionuclide angiography, venography, gastrointestinal bleeding studies, and red cell mass determinations. It is particularly advantageous for RBC labeling in patients receiving chemotherapy

  9. 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 cells...... of reptiles express a different NHE-1 that responds less to volume activation compared to other vertebrates or simply lack the Na+/H+ exchanger. Using various tissues from the ball python (Python regius), Cane toad (Bufo marinus) and European perch (Perca fluviatilis), cDNA libraries were created...

  10. Yersinia enterocolitica septicaemia from transfusion of red cell concentrate stored for 16 days.

    OpenAIRE

    Jones, B L; Saw, M H; Hanson, M F; Mackie, M J; Scott, J; Murphy, W G

    1993-01-01

    Two cases of transfusion transmitted Yersinia enterocolitica biotype 3, serotype 09 infection occurred in south east Scotland within four months of each other. In one case, a 79 year old man died the day after receiving a unit of red cell concentrate that had been stored for 29 days after donation. In the second case a 78 year old man died three days after transfusion of a unit of red cell concentrate that had been collected 16 days before transfusion. The donors of both units had no symptoms...

  11. Preferential radiosensitization of G1 checkpoint--deficient cells by methylxanthines

    International Nuclear Information System (INIS)

    Russell, Kenneth J.; Wiens, Linda W.; Demers, G. William; Galloway, Denise A.; Le, Tiep; Rice, Glenn C.; Bianco, James A.; Singer, Jack W.; Groudine, Mark

    1996-01-01

    Purpose: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. Methods and Materials: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. Results: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. Conclusions: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues

  12. Reconstruction of limbal stem cell deficient corneal surface with induced human bone marrow mesenchymal stem cells on amniotic membrane.

    Science.gov (United States)

    Rohaina, Che Man; Then, Kong Yong; Ng, Angela Min Hwei; Wan Abdul Halim, Wan Haslina; Zahidin, Aida Zairani Mohd; Saim, Aminuddin; Idrus, Ruszymah B H

    2014-03-01

    The cornea can be damaged by a variety of clinical disorders or chemical, mechanical, and thermal injuries. The objectives of this study were to induce bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface defects in a limbal stem cell deficiency model. BMSCs were induced to corneal lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation of corneal stem cell markers; β1-integrin, C/EBPδ, ABCG2, and p63, increased protein expression of CK3 and p63 significantly compared with the uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on amniotic membrane in a transwell co-culture system and were grown in limbal medium. Limbal stem cell deficiency models were induced by alkaline injury, and the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed remarkable improvement in corneal regeneration in terms of corneal clarity and reduced vascularization. Histologic and optical coherence tomography analyses demonstrated comparable corneal thickness and achieved stratified epithelium with a compact stromal layer resembling that of normal cornea. CK3 and p63 were expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced into corneal epithelial lineage, and these cells are viable for the formation of TEC, to be used for the reconstruction of the corneal surface in the limbal stem cell deficient model. Copyright © 2014 Mosby, Inc. All rights reserved.

  13. Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.

    Science.gov (United States)

    Shaw, Kit L; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S; Scharenberg, Andrew; Yang, Otto O; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio; Kohn, Donald B

    2017-05-01

    Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1-2.6) and granulocytes (VCN = 0.01-0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. ClinicalTrials.gov NCT00794508. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA

  14. Lack of oxygen effect in glutathione-deficient human cells in culture

    International Nuclear Information System (INIS)

    Edgren, M.; Larsson, A.; Nilsson, K.; Revesz, L.; Scott, O.C.A.

    1980-01-01

    The frequency of X-ray-induced DNA breaks was determined in human cell lines which are deficient in glutathione synthetase and have a greatly reduced glutathione content. Hydroxyapatite chromatography was used for the estimation of the DNA breaks in cell cultures, which were derived either from lymphoblasts transformed by infection with EB virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in argon, was similar to that found when exposure was made in air. In control cultures with normal glutathione content, the induction of breaks was enhanced when irradiation was made under aerobic, instead of anaerobic, conditions. Treatment of the glutathione-deficient cells with the hypoxic radiosensitizer misonidazole did not enhance the induction of breaks by radiation delivered either in air or in argon. In control cultures, radiation induction of breaks was enhanced by misonidazole under anaerobic but not under aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine however, irradiation in the absence of oxygen resulted in a decreased frequency of DNA breaks. (author)

  15. Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

    Science.gov (United States)

    Bailis, Julie M; Weidmann, Alyson G; Mariano, Natalie F; Barton, Jacqueline K

    2017-07-03

    The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)] 2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

  16. F NMR measurement of intracellular free calcium in human red blood cells

    International Nuclear Information System (INIS)

    Gupta, R.K.; Schanne, F.A.X.

    1986-01-01

    Optical techniques for the measurement of intracellular Ca are not readily applicable to the human red cell because of the intense absorption of hemoglobin. The authors have therefore examined the use of 19 F NMR of 5,5'-difluoro-1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetra acetic acid (5FBAPTA) introduced non-disruptively by intracellular hydrolysis of the membrane-permeant acetoxymethyl ester derivative. 19 F NMR spectra of 5FBAPTA-containing erythrocytes at 188 MHz displayed two well resolved resonances corresponding to the free and Ca-bound forms of the chelator, the resonance of the free form being ten-fold larger than that of the Ca-bound form. Addition of the ionophore A23187 resulted in the disappearance of the resonance of the free anion and a quantitative increase in the intensity of the resonance of the Ca-complex. From these data, and a K/sub D/ of 708 nM for the Ca-5FBAPTA complex, the authors estimate red cell free Ca to be 70 nM, which is in the range of values obtained for other cells, despite the fact that the human red cell, which lacks intracellular organelles for storing Ca, possesses only 1 μmol total Ca/1. cells in comparison to mmols of total Ca found in other cells. The authors ability to use 19 F NMR to measure free Ca in the red blood cell paves the way for future NMR studies of red cell free Ca concentrations in human essential hypertension as well as in other diseases states in which alterations in cellular Ca homeostasis may be involved

  17. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Type 1 diabetes in NOD mice unaffected by mast cell deficiency.

    Science.gov (United States)

    Gutierrez, Dario A; Fu, Wenxian; Schonefeldt, Susann; Feyerabend, Thorsten B; Ortiz-Lopez, Adriana; Lampi, Yulia; Liston, Adrian; Mathis, Diane; Rodewald, Hans-Reimer

    2014-11-01

    Mast cells have been invoked as important players in immune responses associated with autoimmune diseases. Based on in vitro studies, or in vivo through the use of Kit mutant mice, mast cells have been suggested to play immunological roles in direct antigen presentation to both CD4(+) and CD8(+) T cells, in the regulation of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2 polarization, all of which could significantly impact the immune response against self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now, the role of mast cells in the onset and incidence of T1D has only been indirectly tested through the use of low-specificity mast cell inhibitors and activators, and published studies reported contrasting results. Our three laboratories have generated independently two strains of mast cell-deficient nonobese diabetic (NOD) mice, NOD.Cpa3(Cre/+) (Heidelberg) and NOD.Kit(W-sh/W-sh) (Leuven and Boston), to address the effects of mast cell deficiency on the development of T1D in the NOD strain. Our collective data demonstrate that both incidence and progression of T1D in NOD mice are independent of mast cells. Moreover, analysis of pancreatic lymph node cells indicated that lack of mast cells has no discernible effect on the autoimmune response, which involves both innate and adaptive immune components. Our results demonstrate that mast cells are not involved in T1D in the NOD strain, making their role in this process nonessential and excluding them as potential therapeutic targets. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  19. The yeast metacaspase is implicated in oxidative stress response in frataxin-deficient cells.

    Science.gov (United States)

    Lefevre, Sophie; Sliwa, Dominika; Auchère, Françoise; Brossas, Caroline; Ruckenstuhl, Christoph; Boggetto, Nicole; Lesuisse, Emmanuel; Madeo, Frank; Camadro, Jean-Michel; Santos, Renata

    2012-01-20

    Friedreich ataxia is the most common recessive neurodegenerative disease and is caused by reduced expression of mitochondrial frataxin. Frataxin depletion causes impairment in iron-sulfur cluster and heme biosynthesis, disruption of iron homeostasis and hypersensitivity to oxidants. Currently no pharmacological treatment blocks disease progression, although antioxidant therapies proved to benefit patients. We show that sensitivity of yeast frataxin-deficient cells to hydrogen peroxide is partially mediated by the metacaspase. Metacaspase deletion in frataxin-deficient cells results in recovery of antioxidant capacity and heme synthesis. In addition, our results suggest that metacaspase is associated with mitochondrial respiration, intracellular redox control and genomic stability. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. Protective effects of red wine flavonols on 4-hydroxynonenal-induced apoptosis in PC12 cells.

    Science.gov (United States)

    Jang, Young Jin; Kang, Nam Joo; Lee, Ki Won; Lee, Hyong Joo

    2009-08-01

    There is accumulating evidence that a moderate consumption of red wine has health benefits, such as the inhibition of neurodegenerative diseases. Although this is generally attributed to resveratrol, the protective mechanisms and the active substance(s) remain unclear. We examined whether and how red wine extract (RWE) and red wine flavonols quercetin and myricetin inhibited 4-hydroxynonenal (HNE)-induced apoptosis of rat pheochromocytoma PC12 cells. RWE attenuated HNE-induced PC12 cell death in a dose-dependent manner. HNE induced cleavage of poly(ADP-ribose) polymerase, which is involved in DNA repair in the nucleus, and this was inhibited by RWE treatment. Treatment with RWE also inhibited HNE-induced nuclear condensation in PC12 cells. Data of 2',7'-dichlorofluorescin diacetate showed that RWE protected against apoptosis of PC12 cells by attenuating intracellular reactive oxygen species. The cytoprotective effects on HNE-induced cell death were stronger for quercetin and myricetin than for resveratrol. HNE-induced nuclear condensation was attenuated by quercetin and myricetin. These results suggest that the neuroprotective potential of red wine is attributable to flavonols rather than to resveratrol.

  1. Nonreassuring fetal heart rate patterns and nucleated red blood cells in term neonates.

    Science.gov (United States)

    Kovalak, E Ebru; Dede, F Suat; Gelisen, Orhan; Dede, Hulya; Haberal, Ali

    2011-05-01

    The aim of this study was to evaluate the association between nonreassuring fetal heart rate patterns during labor and umbilical cord nucleated red blood cell counts. Nucleated red blood cell data was collected prospectively from 41 singleton term neonates presented with nonreassuring fetal heart rate patterns and/or meconium stained amniotic fluid during labor (study group) and from 45 term neonates without any evidence of nonreassuring fetal status (controls). Umbilical artery pH, blood gases and base excess were also determined to investigate the correlation between independent variables. The median nucleated red blood cells per 100 white blood cells were 13 (range 0-37) in the study group and 8 (range 0-21) in the control group. Stepwise regression analysis have identified meconium stained amniotic fluid (R(2) = 0.15, p patterns. Nucleated red blood cells in the cord blood of newborns were found to be elevated in patients with nonreassuring FHR patterns during labor. However, the wide range and the poor correlation of NRBC count with umbilical artery pH and blood gas values limit its clinical utility as a marker for fetal hypoxia.

  2. Laser ektacytometry and evaluation of statistical characteristics of inhomogeneous ensembles of red blood cells

    Science.gov (United States)

    Nikitin, S. Yu.; Priezzhev, A. V.; Lugovtsov, A. E.; Ustinov, V. D.; Razgulin, A. V.

    2014-10-01

    The paper is devoted to development of the laser ektacytometry technique for evaluation of the statistical characteristics of inhomogeneous ensembles of red blood cells (RBCs). We have analyzed theoretically laser beam scattering by the inhomogeneous ensembles of elliptical discs, modeling red blood cells in the ektacytometer. The analysis shows that the laser ektacytometry technique allows for quantitative evaluation of such population characteristics of RBCs as the cells mean shape, the cells deformability variance and asymmetry of the cells distribution in the deformability. Moreover, we show that the deformability distribution itself can be retrieved by solving a specific Fredholm integral equation of the first kind. At this stage we do not take into account the scatter in the RBC sizes.

  3. Role of IGF-1R in ameliorating apoptosis of GNE deficient cells.

    Science.gov (United States)

    Singh, Reema; Chaudhary, Priyanka; Arya, Ranjana

    2018-05-09

    Sialic acids (SAs) are nine carbon acidic amino sugars, found at the outermost termini of glycoconjugates performing various physiological and pathological functions. SA synthesis is regulated by UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) that catalyzes rate limiting steps. Mutations in GNE result in rare genetic disorders, GNE myopathy and Sialuria. Recent studies indicate an alternate role of GNE in cell apoptosis and adhesion, besides SA biosynthesis. In the present study, using a HEK cell-based model for GNE myopathy, the role of Insulin-like Growth Factor Receptor (IGF-1R) as cell survival receptor protein was studied to counter the apoptotic effect of non-functional GNE. In the absence of functional GNE, IGF-1R was hyposialylated and transduced a downstream signal upon IGF-1 (IGF-1R ligand) treatment. IGF-1 induced activation of IGF-1R led to AKT (Protein Kinase B) phosphorylation that may phosphorylate BAD (BCL2 Associated Death Promoter) and its dissociation from BCL2 to prevent apoptosis. However, reduced ERK (Extracellular signal-regulated kinases) phosphorylation in GNE deficient cells after IGF-1 treatment suggests downregulation of the ERK pathway. A balance between the ERK and AKT pathways may determine the cell fate towards survival or apoptosis. Our study suggests that IGF-1R activation may rescue apoptotic cell death of GNE deficient cell lines and has potential as therapeutic target.

  4. Cobalt uptake and binding in human red blood cells

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... 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......-migrate with hemoglobin in Sephadex column chromatography of a lysate of (57)Co-loaded cells. (57)Co also co-migrates with hemoglobin when added to a lysate of unlabeled cells or to a solution of purified hemoglobin, in both cases with a time-dependent development of tight binding. Cobalt is known to bind to the globin...

  5. Zinc Deficiency Induces Apoptosis via Mitochondrial p53- and Caspase-Dependent Pathways in Human Neuronal Precursor Cells

    Science.gov (United States)

    Seth, Rohit; Corniola, Rikki S.; Gower-Winter, Shannon D.; Morgan, Thomas J., Jr.; Bishop, Brian; Levenson, Cathy W.

    2015-01-01

    Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent…

  6. Nature and incidence of severe limbal stem cell deficiency in Australia and New Zealand.

    Science.gov (United States)

    Bobba, Samantha; Di Girolamo, Nick; Mills, Richard; Daniell, Mark; Chan, Elsie; Harkin, Damien G; Cronin, Brendan G; Crawford, Geoffrey; McGhee, Charles; Watson, Stephanie

    2017-03-01

    This study aimed to determine the nature and incidence of severe limbal stem cell deficiency (LSCD) in Australia and New Zealand. A 1-year pilot surveillance study with a 1-year follow-up period was conducted in association with the Australian and New Zealand Ophthalmic Surveillance Unit. The study included patients reported by practising ophthalmologists on the Surveillance Unit's database. Ophthalmologists were provided with a definition of severe limbal stem cell deficiency, contacted on a monthly basis by the Unit and asked to report newly diagnosed cases. Severe LSCD was defined as at least 6 clock hours of whorl-like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium and superficial corneal neovascularization or conjunctivalization. On average, 286 report cards were sent by the Surveillance Unit to practising ophthalmologists each month (total 3429 over 12 months) and the Unit received an average of 176 responses per month (total 2111; 62% response rate). During the 1-year study period from April 2013 to March 2014, 14 positive cases were reported to the Unit. A range of underlying aetiologies were implicated, with contact lens over-wear and cicatrizing conjunctivitis being the most common (n = 3). This surveillance study is the first worldwide to document the incidence of limbal stem cell deficiency; however, because of study design limitations, it is likely to have been under-reported. It provides novel data on the demographics, clinical conditions and management of patients with limbal stem cell deficiency as reported by treating ophthalmologists. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

  7. Characterization of corneal pannus removed from patients with total limbal stem cell deficiency.

    Science.gov (United States)

    Espana, Edgar M; Di Pascuale, Mario A; He, Hua; Kawakita, Tetsuya; Raju, Vadrevu K; Liu, Chia-Yang; Tseng, Scheffer C G

    2004-09-01

    To determine the epithelial lineage of origin in corneal pannus tissue surgically removed from patients with total limbal stem cell (SC) deficiency. The lineage of origin of the entire conjunctivalized pannus removed from eight corneas with a diagnosis of total limbal SC deficiency was characterized by anti-keratin (K)-3 and anti-K19 monoclonal antibodies. The protein and mRNA of epithelial outgrowth from segments of five such pannus specimens were analyzed by Western blot and reverse transcription-polymerase chain reaction, respectively. Cross sections of all eight specimens showed a stratified epithelium with goblet cells expressing mucin (MUC)-5AC, and a stroma showing blood vessels and inflammatory cell infiltrates. Immunostaining showed full-thickness expression of K19 in the entire pannus of all eight specimens. Expression of K3 was negative in seven patients, but was sporadically positive in a patient with Stevens-Johnson syndrome. In culture, all five pannus specimens generated a compact, small epithelial cell outgrowth, and except for one, reached confluence in 2 to 3 weeks. The K3/K12 pair was expressed by extracts of cell outgrowth from the control limbal epithelial explant, but not in all five pannus specimens. A 60-kDa band of DeltaNp63 was expressed in the control specimen and in all five pannus specimens. Cell outgrowth expressed K3 transcript in three, but none showed K12 transcript. The resultant epithelial phenotype of the pannus tissue was not corneal, as evidenced by the negative staining to cornea-specific K12 mRNA and protein, but was conjunctival, as evidenced by the presence of goblet cells, the weak expression of K3, and the strong expression of K19. The abundant expression of DeltaNp63 in such conjunctiva-derived epithelium in eyes with total limbal SC deficiency raises doubts as to its validity as a limbal SC marker. Copyright Association for Research in Vision and Ophthalmology

  8. Effects of PARP-1 Deficiency on Th1 and Th2 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    M. Sambucci

    2013-01-01

    Full Text Available T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosylation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose polymerases (PARPs. Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+ cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+ cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.

  9. The role of CD4+ T cells in cell-mediated immunity to LCMV: studies in MHC class I and class II deficient mice

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Marker, O; Thomsen, Allan Randrup

    1994-01-01

    Parameters of the virus-specific T-cell response were analysed in order to dissect the contribution of CD4+ and CD8+ T cells to cell-mediated immunity to lymphocytic choriomeningitis virus. In MHC class II deficient mice, initial T-cell responsiveness was not impaired, but virus clearance...... was delayed, and virus-specific Td activity declined more rapidly. Furthermore, class I restricted Tc memory appeared to be impaired in these mice. To directly evaluate the role of CD4+ cells in virus clearance and T-cell mediated inflammation, MHC class I deficient mice were also studied. No virus...... exudate. This low-grade response was associated with some degree of virus control as organ titres were lower in these animals than in matched T-cell deficient nu/nu mice or class I deficient mice treated with anti-CD4 monoclonal antibody. This confirms that CD4+ cells are not needed to induce a virus...

  10. FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells.

    Directory of Open Access Journals (Sweden)

    Alessandro Esposito

    Full Text Available During its intraerythrocytic asexual reproduction cycle Plasmodium falciparum consumes up to 80% of the host cell hemoglobin, in large excess over its metabolic needs. A model of the homeostasis of falciparum-infected red blood cells suggested an explanation based on the need to reduce the colloid-osmotic pressure within the host cell to prevent its premature lysis. Critical for this hypothesis was that the hemoglobin concentration within the host cell be progressively reduced from the trophozoite stage onwards.The experiments reported here were designed to test this hypothesis by direct measurements of the hemoglobin concentration in live, infected red cells. We developed a novel, non-invasive method to quantify the hemoglobin concentration in single cells, based on Förster resonance energy transfer between hemoglobin molecules and the fluorophore calcein. Fluorescence lifetime imaging allowed the quantitative mapping of the hemoglobin concentration within the cells. The average fluorescence lifetimes of uninfected cohorts was 270+/-30 ps (mean+/-SD; N = 45. In the cytoplasm of infected cells the fluorescence lifetime of calcein ranged from 290+/-20 ps for cells with ring stage parasites to 590+/-13 ps and 1050+/-60 ps for cells with young trophozoites and late stage trophozoite/early schizonts, respectively. This was equivalent to reductions in hemoglobin concentration spanning the range from 7.3 to 2.3 mM, in line with the model predictions. An unexpected ancillary finding was the existence of a microdomain under the host cell membrane with reduced calcein quenching by hemoglobin in cells with mature trophozoite stage parasites.The results support the predictions of the colloid-osmotic hypothesis and provide a better understanding of the homeostasis of malaria-infected red cells. In addition, they revealed the existence of a distinct peripheral microdomain in the host cell with limited access to hemoglobin molecules indicating the

  11. Directly observed reversible shape changes and hemoglobin stratification during centrifugation of human and Amphiuma red blood cells.

    Science.gov (United States)

    Hoffman, Joseph F; Inoué, Shinya

    2006-02-21

    This paper describes changes that occur in human and Amphiuma red blood cells observed during centrifugation with a special microscope. Dilute suspensions of cells were layered, in a centrifuge chamber, above an osmotically matched dense solution, containing Nycodenz, Ficoll, or Percoll (Pharmacia) that formed a density gradient that allowed the cells to slowly settle to an equilibrium position. Biconcave human red blood cells moved downward at low forces with minimum wobble. The cells oriented vertically when the force field was increased and Hb sedimented as the lower part of each cell became bulged and assumed a "bag-like" shape. The upper centripetal portion of the cell became thinner and remained biconcave. These changes occurred rapidly and were completely reversible upon lowering the centrifugal force. Bag-shaped cells, upon touching red cells in rouleau, immediately reverted to biconcave disks as they flipped onto a stack. Amphiuma red cells displayed a different type of reversible stratification and deformation at high force fields. Here the cells became stretched, with the nucleus now moving centrifugally, the Hb moving centripetally, and the bottom of the cells becoming thinner and clear. Nevertheless, the distribution of the marginal bands at the cells' rim was unchanged. We conclude that centrifugation, per se, while changing a red cell's shape and the distribution of its intracellular constituents, does so in a completely reversible manner. Centrifugation of red cells harboring altered or missing structural elements could provide information on shape determinants that are still unexplained.

  12. A Pseudomonas aeruginosa strain isolated from a contact lens-induced acute red eye (CLARE) is protease-deficient.

    Science.gov (United States)

    Estrellas, P S; Alionte, L G; Hobden, J A

    2000-03-01

    Pseudomonas aeruginosa proteases are thought to be important virulence factors in the pathogenesis of corneal disease. This study examined protease production from two strains of P. aeruginosa responsible for two very distinct clinical diseases: strain Paer1, isolated from a Contact Lens-induced Acute Red Eye (CLARE), and strain KEI 1025, isolated from a corneal ulcer. Strains were compared to a laboratory strain (ATCC 19660) known to produce severe keratitis in experimentally infected mice for protease production and for ocular virulence. Protease production was examined with colorimetric assays, gelatin zymography and western blots. Elastase A activity was quantitated with a staphylolytic assay. Ocular virulence was examined using a mouse scratch model of keratitis. In contrast to strains KEI 1025 or ATCC 19660, Paer1 was unable to produce enzymatically active elastase A, elastase, and protease IV. All three strains produced active alkaline protease. Strains KEI 1025 and ATCC 19660 produced a fulminant keratitis in mice whereas Paer1 produced a mild transient infection. Restoration of elastase activity in Paer1 via genetic complementation did not result in a virulent phenotype. Co-infection of mouse eyes with strains Paer1 and ATCC 19660 resulted in the eventual loss of Paer1 from corneal tissue. These studies suggest that P. aeruginosa elastase A and/or protease IV, but not alkaline protease or elastase, contribute to the ocular virulence of this organism.

  13. The effect of cyclosporin A on the primary immune response to allogeneic red cells in rabbits.

    Science.gov (United States)

    Smith, G N

    1982-01-01

    Cyclosporin A (CSA) has been used in an attempt to suppress the primary immune response of HgA(A)-negative rabbits to A-positive red cells. The immune response was assessed by measuring the survival of a small intravenous (i.v.) dose of 51Cr-labelled A-positive cells and by testing the serum of the immunized rabbits for anti-A. In one experiment, eight A-negative rabbits were given a first i.v. injection of A-positive red cells, and CSA (25 mg/kg/day) in olive oil was given by mouth for 17-34 days. There was no evidence of impaired alloimmunization compared with the responses in control animals treated with olive oil alone. In a second experiment, eight A-negative rabbits were given a first injection of A-positive muscularly (i.m.), and CSA (25 mg/kg/day) in miglyol was given by im.m. injection for 10 days. Six of these rabbits were rendered unresponsive, and the remaining two, who showed impaired survival of the monitoring red cells, produced only low anit-A titres. Seven out of eight controls given i.m. miglyol without CSA responded with good anti-A production. Rabbits that were unresponsive to A-positive red cells responded normally to sheep red blood cells 15 weeks after CSA treatment. Higher serum levels of CSA were found following i.m. administration of the drug but treatment by this route as associated with severe toxicity in some rabbits. PMID:7056563

  14. Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

    Directory of Open Access Journals (Sweden)

    Charlton HM

    2003-02-01

    Full Text Available Abstract During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI, 17β-hydroxysteroid dehydrogenase type III (17βHSD III, prostaglandin D (PGD-synthetase and oestrogen sulphotransferase (EST is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH.

  15. Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye.

    Science.gov (United States)

    Lin, Hui; Li, Wei; Dong, Nuo; Chen, Wensheng; Liu, Jing; Chen, Lelei; Yuan, Hongxia; Geng, Zhixin; Liu, Zuguo

    2010-01-01

    To investigate the morphology, distribution, and density of inflammatory cells in the corneal epithelium of aqueous tear-deficient dry eye. Thirty-two patients with non-Sjögren's syndrome (NSS) dry eye, 14 patients with Sjögren's syndrome (SS) dry eye, and 33 healthy volunteers were studied. In vivo laser scanning confocal microscopy was used to investigate both Langerhans cell (LCs) and leukocyte distribution and density in the peripheral and central corneal epithelium. LC morphology was also evaluated. Multifactor regression analysis assessed whether there is a correlation between clinical manifestations and inflammatory cell densities. LCs were present in both central (34.9 +/- 5.7 cells/mm(2)) and peripheral (90.7 +/- 8.2 cells/mm(2)) parts of the normal corneal epithelium. Moreover, LC density increased dramatically in the central corneal epithelium in patients with NSS (89.8 +/- 10.8 cells/mm(2)) and SS (127.9 +/- 23.7 cells/mm(2)). The ratio of LCs with obvious processes was much higher in patients with dry eye than in healthy volunteers. LC density also increased in peripheral corneal epithelium in patients with SS, but not in those with NSS. Leukocyte density in normal corneal epithelium was very low, whereas it increased in the central corneal epithelium (4.6 +/- 1.0 cells/mm(2)) in NSS and in both central (49.0 +/- 12.9 cells/mm(2)) and peripheral (84.2 +/- 36.8 cells/mm(2)) corneal epithelium in SS. Densities of LCs and leukocytes showed significant correlation with the severity found in clinical evaluation. The LC and leukocyte changes in the corneal epithelium suggest their involvement in aqueous tear-deficient dry eye pathophysiology. In vivo dynamic assessment of central corneal inflammatory cell density may serve as an indicator of dry eye severity and provide new insight for dry eye treatment.

  16. Establishment of HeLa cell mutants deficient in sphingolipid-related genes using TALENs.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Yamaji

    Full Text Available Sphingolipids are essential components in eukaryotes and have various cellular functions. Recent developments in genome-editing technologies have facilitated gene disruption in various organisms and cell lines. We here show the disruption of various sphingolipid metabolic genes in human cervical carcinoma HeLa cells by using transcription activator-like effector nucleases (TALENs. A TALEN pair targeting the human CERT gene (alternative name COL4A3BP encoding a ceramide transport protein induced a loss-of-function phenotype in more than 60% of HeLa cells even though the cell line has a pseudo-triploid karyotype. We have isolated several loss-of-function mutant clones for CERT, UGCG (encoding glucosylceramide synthase, and B4GalT5 (encoding the major lactosylceramide synthase, and also a CERT/UGCG double-deficient clone. Characterization of these clones supported previous proposals that CERT primarily contributes to the synthesis of SM but not GlcCer, and that B4GalT5 is the major LacCer synthase. These newly established sphingolipid-deficient HeLa cell mutants together with our previously established stable transfectants provide a 'sphingolipid-modified HeLa cell panel,' which will be useful to elucidate the functions of various sphingolipid species against essentially the same genomic background.

  17. Role of hemolysis in red cell adenosine triphosphate release in simulated exercise conditions in vitro.

    Science.gov (United States)

    Mairbäurl, Heimo; Ruppe, Florian A; Bärtsch, Peter

    2013-10-01

    Specific adenosine triphosphate (ATP) release from red blood cells has been discussed as a possible mediator controlling microcirculation in states of decreased tissue oxygen. Because intravascular hemolysis might also contribute to plasma ATP, we tested in vitro which portion of ATP release is due to hemolysis in typical exercise-induced strains to the red blood cells (shear stress, deoxygenation, and lactic acidosis). Human erythrocytes were suspended in dextran-containing media (hematocrit 10%) and were exposed to shear stress in a rotating Couette viscometer at 37°C. Desaturation (oxygen saturation of hemoglobin ∼20%) was achieved by tonometry with N2 before shear stress exposure. Cells not exposed to shear stress were used as controls. Na lactate (15 mM), lactic acid (15 mM, pH 7.0), and HCl (pH 7.0) were added to simulate exercise-induced lactic acidosis. After incubation, extracellular hemoglobin was measured to quantify hemolysis. ATP was measured with the luciferase assay. Shear stress increased extracellular ATP in a stress-related and time-dependent manner. Hypoxia induced a ∼10-fold increase in extracellular ATP in nonsheared cells and shear stress-exposed cells. Lactic acid had no significant effect on ATP release and hemolysis. In normoxic cells, approximately 20%-50% of extracellular ATP was due to hemolysis. This proportion decreased to less than 10% in hypoxic cells. Our results indicate that when exposing red blood cells to typical strains they encounter when passing through capillaries of exercising skeletal muscle, ATP release from red blood cells is caused mainly by deoxygenation and shear stress, whereas lactic acidosis had only a minor effect. Hemolysis effects were decreased when hemoglobin was deoxygenated. Together, by specific release and hemolysis, extracellular ATP reaches values that have been shown to cause local vasodilatation.

  18. Historical time trends in red blood cell usage in the Netherlands

    NARCIS (Netherlands)

    van Hoeven, Loan R; Koopman, Maria M W; Koffijberg, Hendrik; Roes, Kit C.B.; Janssen, Mart P

    2016-01-01

    Background: While the number of hospitalized patients in Dutch hospitals has increased since 1997, the demand for red blood cell units (RBCs) has simultaneously decreased. This implies a dramatic change in transfusion practice toward fewer blood transfusions on average per patient. Objectives: In

  19. Historical time trends in red blood cell usage in the Netherlands

    NARCIS (Netherlands)

    van Hoeven, L.R.; Koopman, M.M.W.; Koffijberg, Hendrik; Roes, K.C.B.; Janssen, M.P.

    2016-01-01

    Background: While the number of hospitalized patients in Dutch hospitals has increased since 1997, the demand for red blood cell units (RBCs) has simultaneously decreased. This implies a dramatic change in transfusion practice toward fewer blood transfusions on average per patient.Objectives: In

  20. A method for red blood cell biotinylation in a closed system

    NARCIS (Netherlands)

    de Back, Djuna Z.; Vlaar, Richard; Beuger, Boukje; Daal, Brunette; Lagerberg, Johan; Vlaar, Alexander P. J.; de Korte, Dirk; van Kraaij, Marian; van Bruggen, Robin

    2018-01-01

    Several circumstances require the accurate measurement of red blood cell (RBC) survival and clearance, such as determination of posttransfusion recovery of stored RBCs to investigate the effect of new additive solutions. To this end, biotin as a marker of RBCs to track donor RBCs in the blood of the

  1. Survival of the fittest?--survival of stored red blood cells after transfusion.

    NARCIS (Netherlands)

    Luten, M.; Roerdinkholder-Stoelwinder, B.; Bost, H.J.; Bosman, G.J.C.G.M.

    2004-01-01

    During the last 90 years many developments have taken place in the world of blood transfusion. Several anticoagulants and storage solutions have been developed. Also the blood processing has undergone many changes. At the moment, in The Netherlands, red blood cell (RBC) concentrates (prepared from a

  2. Glucose-6-phosphate dehydrogenase activity decreases during storage of leukoreduced red blood cells

    NARCIS (Netherlands)

    Peters, Anna L.; van Bruggen, Robin; de Korte, Dirk; van Noorden, Cornelis J. F.; Vlaar, Alexander P. J.

    2016-01-01

    During storage, the activity of the red blood cell (RBC) antioxidant system decreases. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection against oxidative stress by producing NADPH. G6PD function of RBC transfusion products is reported to remain stable during storage, but activity

  3. Exercise performance, red blood cell deformability, and lipid peroxidation: effects of fish oil and vitamin E

    NARCIS (Netherlands)

    Oostenbrug, G. S.; Mensink, R. P.; Hardeman, M. R.; de Vries, T.; Brouns, F.; Hornstra, G.

    1997-01-01

    Previous studies have indicated that fish oil supplementation increases red blood cell (RBC) deformability, which may improve exercise performance. Exercise alone, or in combination with an increase in fatty acid unsaturation, however, may enhance lipid peroxidation. Effects of a bicycle time trial

  4. Haemolysis following rapid experimental red blood cell transfusion--an evaluation of two infusion pumps

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Sprogøe-Jakobsen, U; Pedersen, C M

    1998-01-01

    The vast majority of infusion pumps used for rapid transfusion of large amounts of blood have never been properly examined regarding their influence on the quality of the red blood cells (RBCs) infused. In this study, we evaluated the effect of two different infusion pumps on the degree of RBC...

  5. Study on the relationship between red blood cell immunity and lipid peroxidation in patients with endometriosis

    International Nuclear Information System (INIS)

    Yang Jingxiu; Shi Shaohong; Wang Yuping; Xie Xueqin; Qin Jibao

    2005-01-01

    Objective: To assess the relationship between red blood cell immunity and lipid peroxidation (LPO) in patients with endometriosis. Methods: The percentage of positive red blood cell c3b receptor rosette (RBC c3b -RR) and red blood cell immune complex rosette (RBC-ICR) were examined in 54 patients with endometriosis and 30 controls. Serum levels of malondialdehyde (MDA), superoxidase (SOD) and glutathione peroxidase (GSH-PX) were measured by chemocolorimetry in these subjects. Results: Percentage of positive RBC-ICR and MDA levels were significantly higher in patients with endometriosis than those in controls (P c3b RR, SOD, GSH-PX, SOD/MDA ratio were significantly lower in patients with endometriosis than those in controls (P c3b -RR was negatively correlated with MDA levels (r= -0. 4428, P < 0.05) and RBC-ICRR was positively correlated with MDA(r=0.5488, P0.05). Conclusion: The lower red cell immune adhesion function was closely associated with the disturbance of metabolism of lipid peroxidation in patients with endometriosis. (authors)

  6. The proteome of red cell membranes and vesicles during storage in blood bank conditions.

    NARCIS (Netherlands)

    Bosman, G.J.C.G.M.; Lasonder, E.; Luten, M.; Roerdinkholder-Stoelwinder, B.; Novotny, V.M.J.; Bos, H.; Grip, W.J. de

    2008-01-01

    BACKGROUND: During storage of red cells (RBCs) for transfusion, RBCs undergo a number of biochemical and morphologic changes. To be able to identify the mechanisms underlying these storage lesions, a proteomic analysis of the membranes of RBCs and their vesicles was performed during various periods

  7. First haemorheological experiment on NASA space shuttle 'Discovery' STS 51-C: aggregation of red cells.

    Science.gov (United States)

    Dintenfass, L; Osman, P D; Jedrzejczyk, H

    1985-01-01

    The 'secret' D.O.D. Mission on flight STS 51-C also carried nearly 100 kg of automated instrumentation of the Australian experiment on aggregation of red cells ("ARC"). The automated Slit-Capillary Photo Viscometer contained blood samples from subjects with history of coronary heart disease, cancer of the colon, insulin-dependent diabetes, etc., as well as normals. The experiment ran for nine hours, according to the program of its microcomputers. When shuttle landed and instrumentation recovered and opened in the presence of NASA quality control officers, it was obvious that experiment was a success. Tentative and preliminary results can be summarized as follows: red cells did not change shape under zero gravity; red cells do aggregate under zero gravity, although the size of aggregates is smaller than on the ground; the morphology of aggregates of red cells appears to be of rouleaux type under zero gravity, notwithstanding the fact that pathological blood was used. These results will have to be confirmed in the future flights. The background and history of development of the project are described, and put into context of our general haemorheological studies.

  8. MORPHOMETRIC CHARACTERISTICS OF RED BLOOD CELLS OF Telestes metohiensis (Steindachner, 1901

    Directory of Open Access Journals (Sweden)

    Radoslav Dekić

    2013-02-01

    Full Text Available The paper presents the morphometric characteristics of red blood cells of endemic fish species of Bosnia and Herzegovina, Telestes metohiensis (Steindachner, 1901 inhabiting the Vrijeka river in the Dabar field. A total of 30 fish were sampled during August, 2010. Morphological measurements included the following parameters: axes of the red blood cells and nuclei, the surface of the red blood cells and nuclei and the thickness of the red blood cells. Morphometric characteristics of the erythrocyte maturation stages (acidophilic and polychromatic erythroblasts were also studied as well as their proportion in the peripheral blood. 100 mature forms were measured for each individual. The propotion of the immature forms was expressed per 1000 erythrocytes. Results showed that dimensions of the erythrocytes differed in systematic categories as well as fish types. Dimensions of mature erythrocytes and their maturation stages of the same species differed in shape and size of the nuclei. Proportion of the erythrocyte maturation stages was very low in comparison with the mature erythrocytes, indicating the optimal environmental conditions for the studied species.Key words: morphometric characteristics, erythrocytes, Telestes metohiensis, proportion of immature stages

  9. Mechanics of extracellular vesicles derived from malaria parasiteinfected Red Blood Cells

    NARCIS (Netherlands)

    Sorkin, Raya; Vorselen, Daan; Ofir-Birin, Yifat; Roos, Wouter H.; MacKintosh, Fred C.; Regev-Rudzki, Neta; Wuite, Gijs J. L.

    2016-01-01

    Malaria is a life-threatening disease caused by parasites that are transmitted through the bites of infected mosquitoes, with Plasmodium falciparum (Pf) causing the most severe form of malaria (1). Very recently it was discovered that Pf infected red blood cells (iRBC) directly transfer information

  10. The dual roles of red blood cells in tissue oxygen delivery

    DEFF Research Database (Denmark)

    Jensen, Frank Bo

    2009-01-01

    Vertebrate red blood cells (RBCs) seem to serve tissue oxygen delivery in two distinct ways. Firstly, RBCs enable the adequate transport of O2 between respiratory surfaces and metabolizing tissues by means of their high intracellular concentration of hemoglobin (Hb), appropriate allosteric...

  11. Automatic tracking of red blood cells in micro channels using OpenCV

    Science.gov (United States)

    Rodrigues, Vânia; Rodrigues, Pedro J.; Pereira, Ana I.; Lima, Rui

    2013-10-01

    The present study aims to developan automatic method able to track red blood cells (RBCs) trajectories flowing through a microchannel using the Open Source Computer Vision (OpenCV). The developed method is based on optical flux calculation assisted by the maximization of the template-matching product. The experimental results show a good functional performance of this method.

  12. Women's attitude towards prenatal screening for red blood cell antibodies, other than RhesusD

    NARCIS (Netherlands)

    Koelewijn, Joke M.; Vrijkotte, Tanja G. M.; de Haas, Masja; van der Schoot, C. E.; Bonsel, Gouke J.

    2008-01-01

    ABSTRACT: BACKGROUND: Since July 1998 all Dutch women (+/- 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for

  13. Women's attitude towards prenatal screening for red blood cell antibodies, other than RhD

    NARCIS (Netherlands)

    J. Koelewijn; T.G.M. Vrijkotte (Tanja); M. de Haas; C.E. van der Schoot (Ellen); G.J. Bonsel (Gouke)

    2008-01-01

    textabstractBackground: Since July 1998 all Dutch women (± 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for

  14. Survival of Er(a+) red cells in a patient with allo-anti-Era

    International Nuclear Information System (INIS)

    Thompson, H.W.; Skradski, K.J.; Thoreson, J.R.; Polesky, H.F.

    1985-01-01

    51 Chromium-labeled Er(a+) red cells survived nearly normally (T1/2 of 21 days) in a patient with allo-anti-Era. Transfusion of Er(a+) blood was without significant reaction and did not affect the anti-Era titer

  15. Adverse effects to transfusion with red donor blood cells are frequent

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Nørgaard, Astrid; Burcharth, Jakob

    2014-01-01

    Adverse effects to transfusion with red donor blood cells are potentially life-threatening. Due to screening, transmission of infectious diseases has decreased; however, the risk is still present. Various immune reactions are common including simple allergic reactions as well as devastating...

  16. Photometric measurements of red blood cell aggregation: light transmission versus light reflectance

    NARCIS (Netherlands)

    Baskurt, O.K.; Uyuklu, M.; Hardeman, M.R.; Meiselman, H.J.

    2009-01-01

    Red blood cell (RBC) aggregation is the reversible and regular clumping in the presence of certain macromolecules. This is a clinically important phenomenon, being significantly enhanced in the presence of acute phase reactants (e. g., fibrinogen). Both light reflection (LR) and light transmission

  17. Photometric measurements of red blood cell aggregation: light transmission versus light reflectance

    NARCIS (Netherlands)

    Baskurt, Oguz K.; Uyuklu, Mehmet; Hardeman, Max R.; Meiselman, Herbert J.

    2009-01-01

    Red blood cell (RBC) aggregation is the reversible and regular clumping in the presence of certain macromolecules. This is a clinically important phenomenon, being significantly enhanced in the presence of acute phase reactants (e.g., fibrinogen). Both light reflection (LR) and light transmission

  18. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

    NARCIS (Netherlands)

    Chami, N. (Nathalie); M.-H. Chen (Ming-Huei); Slater, A.J. (Andrew J.); Eicher, J.D. (John D.); E. Evangelou (Evangelos); Tajuddin, S.M. (Salman M.); Love-Gregory, L. (Latisha); T. Kacprowski (Tim); U.M. Schick (Ursula); Nomura, A. (Akihiro); Giri, A. (Ayush); Lessard, S. (Samuel); J. Brody (Jennifer); C. Schurmann (Claudia); V.S. Pankratz (Shane); L.R. Yanek (Lisa); A. Manichaikul (Ani); R. Pazoki (Raha); E. Mihailov (Evelin); W.D. Hill (W. David); Raffield, L.M. (Laura M.); A.D. Burt (Alastair); T.M. Bartz (Traci M.); D.M. Becker (Diane); L.C. Becker (Lewis); E.A. Boerwinkle (Eric); J. Bork-Jensen (Jette); E.P. Bottinger (Erwin); M.L. O'Donoghue (Michelle L.); D.R. Crosslin (David); de Denus, S. (Simon); Dubé, M.-P. (Marie-Pierre); P. Elliott (Paul); G. Engström; M. Evans (Michele); J. Floyd (James); M. Fornage (Myriam); Gao, H. (He); A. Greinacher (Andreas); V. Gudnason (Vilmundur); T. Hansen (T.); T.B. Harris (Tamara); C. Hayward (Caroline); Hernesniemi, J. (Jussi); H. Highland (Heather); J.N. Hirschhorn (Joel); Hofman, A. (Albert); Irvin, M.R. (Marguerite R.); M. Kähönen (Mika); E.M. Lange (Ethan); Launer, L.J. (Lenore J.); T. Lehtimäki (Terho); Li, J. (Jin); D.C. Liewald (David C.); A. Linneberg (Allan); Y. Liu (YongMei); Y. Lu (Yingchang); L.-P. Lyytikäinen (Leo-Pekka); R. Mägi (Reedik); J. Mathias (Jasmine); O. Melander (Olle); A. Metspalu (Andres); K. Mononen (Kari); M.A. Nalls (Michael); D.A. Nickerson (Deborah); K. Nikus (Kjell); C.J. O'Donnell (Christopher); M. Orho-Melander (Marju); O. Pedersen (Oluf); A. Petersmann (Astrid); Polfus, L. (Linda); B.M. Psaty (Bruce); O.T. Raitakari (Olli T.); Raitoharju, E. (Emma); Richard, M. (Melissa); K.M. Rice (Kenneth); F. Rivadeneira Ramirez (Fernando); Rotter, J.I. (Jerome I.); Schmidt, F. (Frank); A.V. Smith (Albert Vernon); J.M. Starr (John); K.D. Taylor (Kent); A. Teumer (Alexander); Thuesen, B.H. (Betina H.); Torstenson, E.S. (Eric S.); R.P. Tracy (Russell); I. Tzoulaki; N.A. Zakai (Neil); Vacchi-Suzzi, C. (Caterina); C.M. van Duijn (Cornelia); F.J.A. van Rooij (Frank); M. Cushman (Mary Ann); I.J. Deary (Ian J.); Velez Edwards, D.R. (Digna R.); Vergnaud, A.-C. (Anne-Claire); L.C. Wallentin (Lars); D. Waterworth (Dawn); White, H.D. (Harvey D.); J.F. Wilson (James); A.B. Zonderman; S. Kathiresan (Sekar); N. Grarup (Niels); T. Esko (Tõnu); R.J.F. Loos (Ruth); L.A. Lange (Leslie); Faraday, N. (Nauder); Abumrad, N.A. (Nada A.); T.L. Edwards (Todd L.); S.K. Ganesh (Santhi); P. Auer (Paul); A.D. Johnson (Andrew); A. Reiner (Alexander); G. Lettre (Guillaume)

    2016-01-01

    textabstractRed blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an

  19. Cardiac arrest due to hyperkalemia following irradiated packed red cells transfusion

    Energy Technology Data Exchange (ETDEWEB)

    Miyazawa, Kazuharu [Yamamoto-kumiai General Hospital, Noshiro, Akita (Japan); Ohta, Sukejuurou; Kojima, Yukiko; Mizunuma, Takahide; Nishikawa, Toshiaki

    1998-11-01

    We describe two cases of cardiac arrest due to hyperkalemia following transfusion of irradiated packed red cells. Case 1: Because sudden, rapid and massive hemorrage occurred in a 69-year-old male patient undergoing the left lobectomy of the liver, 8 units of irradiated packed red cells were rapidly transfused, the patient developed cardiac arrest. Serum kalium concentration after transfusion was 7.6 mEq/l. Case 2: A 7-month-old girl scheduled for closure of a ventricular septal defect, developed cardiac arrest due to hyperkalemia at the start of cardiopulmonary bypass. The extracorporeal circuit was primed with 6 units of irradiated packed red blood cells. Serum kalium concentration immediately after the start of cardiopulmonary bypass was 10.6 mEq/l. Analysis of kalium concentration in the pilot tubes of the same packs revealed 56-61 mEq/l. These case reports suggest that fresh irradiated packed red cells should be transfused during massive bleeding and for pediatric patients to prevent severe hyperkalemia. (author)

  20. Relation of mean platelet volume and red blood cell distribution width with epistaxis.

    Science.gov (United States)

    Kemal, Ozgur; Müderris, Togay; Sevil, Ergün; Kutlar, Gökhan

    2015-04-01

    Mean platelet volume is the measurement of the average size of platelets in the blood, and red blood cell distribution width is the variability of the size of red blood cells in circulation. This study aimed to investigate if there was any relationship between mean platelet volume, red blood cell distribution, and epistaxis. Prospective controlled trial. The study included 90 patients admitted to Ankara Atatürk Hospital and Samsun Medicana Hospital with complaints of recurrent epistaxis, and a control group of 90 healthy subjects. Blood samples were taken from all patients and control group subjects. Mean platelet volume and red blood cell distribution parameters were examined and compared between the two groups. The mean platelet volume levels were determined as 8.86 ± 0.1 in the control group and 8.36 ± 0.1 in the patient group. The difference between the two groups with respect to mean platelet volume was statistically significant (P epistaxis. These findings could be beneficial in new investigations into epistaxis mechanisms. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Physiological implications of seasonal variation in membrane-associated calcium in red spruce mesophyll cells

    Science.gov (United States)

    D.H. DeHayes; P.G. Schaberg; G.J. Hawley; C.H. Borer; J.R. Cumming; J.R. Strimbeck

    1997-01-01

    We examined the pattern of seasonal variation in total foliar calcium (Ca) pools and plasma membrane-associated Ca (mCa) in mesophyll cells of current-year and 1-year-old needles of red spruce (Picea rubens Sarg.) and the relationship between mCa and total foliar Ca on an individual plant and seasonal basis. Foliar samples were collected from...

  2. Seventy-five genetic loci influencing the human red blood cell

    NARCIS (Netherlands)

    van der Harst, P.; Zhang, W.; Mateo Leach, I.; Rendon, A.; Verweij, N.; Sehmi, J.; Paul, D.S.; Elling, U.; Allayee, H.; Li, X.; Radhakrishnan, A.; Tan, S.T.; Voss, K.; Weichenberger, C.X.; Albers, C.A.; Al-Hussani, A.; Asselbergs, F.W.; Ciullo, M.; Danjou, F.; Dina, C.; Esko, T.; Evans, D.M.; Franke, L.; Gogele, M.; Hartiala, J.; Hersch, M.; Holm, H.; Hottenga, J.J.; Kanoni, S.; Kleber, M.E.; Lagou, V.; Langenberg, C.; Lopez, L.M.; Lyytikainen, L.P.; Melander, O.; Murgia, F.; Nolte, I.M.; O'Reilly, P.F.; Padmanabhan, S.; Parsa, A.; Pirastu, N.; Porcu, E.; Portas, L.; Prokopenko, I.; Ried, J.S.; Shin, S.Y.; Tang, C.S.; Teumer, A.; Traglia, M.; Ulivi, S.; Westra, H.J.; Yang, J.; Zhao, J.H.; Anni, F.; Abdellaoui, A.; Attwood, A.; Balkau, B.; Bandinelli, S.; Bastardot, F.; Benyamin, B.; Boehm, B.O.; Cookson, W.O.; Das, D; de Bakker, P.I.; de Boer, R.A.; de Geus, E.J.; de Moor, M.H.; Dimitriou, M.; Domingues, F.S.; Doring, A.; Engstrom, G.; Eyjolfsson, G.I.; Ferrucci, L.; Fischer, K.; Galanello, R.; Garner, S.F.; Genser, B.; Gibson, Q.D.; Girotto, G.; Gudbjartsson, D.F.; Harris, S.E.; Hartikainen, A.L.; Hastie, C.E.; Hedblad, B.; Illig, T.; Jolley, J.; Kahonen, M.; Kema, I.P.; Kemp, J.P.; Liang, L.; Lloyd-Jones, H.; Loos, R.J.; Meacham, S.; Medland, S.E.; Meisinger, C.; Memari, Y.; Mihailov, E.; Miller, K.; Moffatt, M.F.; Nauck, M., et al.

    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

  3. Anti·red cell activity of lymphocytotoxic antibodies: and in vitro and in ...

    African Journals Online (AJOL)

    The need to obtain non-toxic antilymphocyre sera (ALS) led to the in vitro and in vivo evaluarion of its crossreactivity for red cells. The findings showed thar the antibodies coating the erythrocytes in vitro are idenrical with the antibodies that sensitize lymphocytes by the cytotoxicity rest. It would appear that rhe observed ...

  4. Split dose recovery studies using homologous recombination deficient gene knockout chicken B lymphocyte cells

    International Nuclear Information System (INIS)

    Rao, B.S.S.; Tano, Kaori; Utsumi, Hiroshi; Takeda, Shunichi

    2007-01-01

    To understand the role of proteins involved in double strand breaks (DSB) repair modulating sublethal damage (SLD) recovery, chicken B lymphoma (DT 40) cell lines either proficient or deficient in RAD52, XRCC2, XRCC3, RAD51C and RAD51D were subjected to fractionated irradiation and their survival curves charted. Survival curves of both WT DT40 and RAD52 -/- cells had a big shoulder while all the other cells exhibited small shoulders. However, at the higher doses of radiation, RAD51C -/- cells displayed hypersensitivity comparable to the data obtained for the homologous recombination deficient RAD54 -/- cells. Repair of SLD was measured as an increase in survival after a split dose irradiation with an interval of incubation between the radiation doses. All the cell lines (parental DT40 and genetic knockout cell lines viz., RAD52 -/- , XRCC2 -/- XRCC3 -/- RAD51C -/- and RAD51D -/- ) used in this study demonstrated a typical split-dose recovery capacity with a specific peak, which varied depending on the cell type. The maximum survival of WT DT40 and RAD52 -/- was reached at about 1-2 hours after the first dose of radiation and then decreased to a minimum thereafter (5 h). The increase in the survival peaked once again by about 8 hours. The survival trends observed in XRCC2 -/- , XRCC3 -/- , RAD51C -/- and RAD51D -/- knockout cells were also similar, except for the difference in the initial delay of a peak survival for RAD51D -/- and lower survival ratios. The second phase of increase in the survival in these cell lines was much slower in XRCC2 -/- , XRCC3 -/- , RAD51C -/- nd RAD51D -/- and further delayed when compared with that of RAD52 -/- and parental DT40 cells suggesting a dependence on their cell cycle kinetics. This study demonstrates that the participation of RAD52, XRCC2, XRCC3, RAD51C and RAD51D in the DSB repair via homologous recombination is of less importance in comparison to RAD54, as RAD54 deficient cells demonstrated complete absence of SLD recovery

  5. Relative deformability of red blood cells in sickle cell trait and sickle cell anemia by trapping and dragging

    Science.gov (United States)

    Solomon, Rance; Cooper, James; Welker, Gabriel; Aguilar, Elaura; Flanagan, Brooke; Pennycuff, Chelsey; Scott, David; Farone, Anthony; Farone, Mary; Erenso, Daniel; Mushi, Robert; del Pilar Aguinaga, Maria

    2013-06-01

    Genetic mutation of the β-globin gene or inheritance of this mutated gene changes the chemical composition of the oxygen-carrying hemoglobin molecule that could lead to either the heterozygote genotype, resulting in sickle cell trait (SCT), or the homozygote genotype, resulting in sickle cell anemia (SCA). These mutations could affect the reversible elastic deformations of the red blood cells (RBCs) which are vital for biological functions. We have investigated this effect by studying the differences in the deformability of RBCs from blood samples of an individual with SCT and an untreated patient with SCA along with hemoglobin quantitation of each blood sample. Infrared 1064 nm laser trap force along with drag shear force are used to induce deformation in the RBCs. Ultra2-High Performance Liquid Chromatography (UHPLC) is used for the hemoglobin quantitation.

  6. Transfusion rate and prevalence of unexpected red blood cell alloantibodies in women undergoing hysterectomy for benign disease

    DEFF Research Database (Denmark)

    Thoestesen, Lisbeth M; Rasmussen, Kjeld L; Lauszus, Finn F

    2011-01-01

    To determine transfusion rates, risk factors for transfusion and the prevalence of unexpected red blood cell alloantibodies in women undergoing hysterectomy for benign disease. In addition, we aimed to evaluate the necessity of the pretransfusion testing for red blood cell alloantibodies....

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

    African Journals Online (AJOL)

    SERVER

    2008-04-03

    Apr 3, 2008 ... with micronuclei and 17 ± 0.005 mg/kg of total chrome in tissues, detected through atomic absorption spectrophotometry. .... and human cell lines, DNA damage induction by potas- .... Effects of metallic ion toxicity on human ...

  8. Red blood cells serve as intravascular carriers of myeloperoxidase

    Czech Academy of Sciences Publication Activity Database

    Adam, M.; Gajdová, Silvie; Kolářová, Hana; Kubala, Lukáš; Lau, D.; Geisler, A.

    2014-01-01

    Roč. 74, SEP (2014), s. 353-363 ISSN 0022-2828 R&D Projects: GA ČR(CZ) GCP305/12/J038 Institutional support: RVO:68081707 Keywords : Myeloperoxidase * Erythrocyte * Cell membranes Subject RIV: BO - Biophysics Impact factor: 4.655, year: 2014

  9. Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease.

    Science.gov (United States)

    Casas, Jessica; Friedman, David F; Jackson, Tannoa; Vege, Sunitha; Westhoff, Connie M; Chou, Stella T

    2015-06-01

    Extended red blood cell (RBC) antigen matching is recommended to limit alloimmunization in patients with sickle cell disease (SCD). DNA-based testing to predict blood group phenotypes has enhanced availability of antigen-negative donor units and improved typing of transfused patients, but replacement of routine serologic typing for non-ABO antigens with molecular typing for patients has not been reported. This study compared the historical RBC antigen phenotypes obtained by hemagglutination methods with genotype predictions in 494 patients with SCD. For discrepant results, repeat serologic testing was performed and/or investigated by gene sequencing for silent or variant alleles. Seventy-one typing discrepancies were identified among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing were obtained for 66 discrepancies and retyping agreed with the genotype in 64 cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was found by direct sequencing of JK to be a silenced allele, and one N typing discrepancy remains under investigation. Fifteen false-negative serologic results were associated with alleles encoding weak antigens or single-dose Fy(b) expression. DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens compared to hemagglutination methods, leading to its implementation as the primary method for extended RBC typing for patients with SCD at our institution. © 2015 AABB.

  10. On the Effects of Reactive Oxygen Species and Nitric Oxide on Red Blood Cell Deformability

    Directory of Open Access Journals (Sweden)

    Lukas Diederich

    2018-05-01

    Full Text Available The main function of red blood cells (RBCs is the transport of respiratory gases along the vascular tree. To fulfill their task, RBCs are able to elastically deform in response to mechanical forces and, pass through the narrow vessels of the microcirculation. Decreased RBC deformability was observed in pathological conditions linked to increased oxidative stress or decreased nitric oxide (NO bioavailability, like hypertension. Treatments with oxidants and with NO were shown to affect RBC deformability ex vivo, but the mechanisms underpinning these effects are unknown. In this study we investigate whether changes in intracellular redox status/oxidative stress or nitrosation reactions induced by reactive oxygen species (ROS or NO may affect RBC deformability. In a case-control study comparing RBCs from healthy and hypertensive participants, we found that RBC deformability was decreased, and levels of ROS were increased in RBCs from hypertensive patients as compared to RBCs from aged-matched healthy controls, while NO levels in RBCs were not significantly different. To study the effects of oxidants on RBC redox state and deformability, RBCs from healthy volunteers were treated with increasing concentrations of tert-butylhydroperoxide (t-BuOOH. We found that high concentrations of t-BuOOH (≥ 1 mM significantly decreased the GSH/GSSG ratio in RBCs, decreased RBC deformability and increased blood bulk viscosity. Moreover, RBCs from Nrf2 knockout (KO mice, a strain genetically deficient in a number of antioxidant/reducing enzymes, were more susceptible to t-BuOOH-induced impairment in RBC deformability as compared to wild type (WT mice. To study the role of NO in RBC deformability we treated RBC suspensions from human volunteers with NO donors and nitrosothiols and analyzed deformability of RBCs from mice lacking the endothelial NO synthase (eNOS. We found that NO donors induced S-nitrosation of the cytoskeletal protein spectrin, but did not affect

  11. Effects of iron supplementation on red blood cell hemoglobin content in pregnancy

    Directory of Open Access Journals (Sweden)

    Margreet Schoorl

    2012-11-01

    Full Text Available Although a mild degree of anemia is common in the third trimester of pregnancy, it remains a challenge to establish whether a decrease in hemoglobin (Hb concentration is physiological or pathological. The World Health Organization suggested a Hb concentration of 110 g/L to discriminate anemia. Several European investigators recommended Hb cut-off values of between 101-110 g/L. The aim of this study was to establish short-term effects of iron supplementation on the hemoglobin content of reticulocytes (Ret-He and red blood cells (RBC-He in case of suspected iron deficient erythropoiesis (IDE in the third trimester of pregnancy. Twenty-five subjects with suspected IDE during pregnancy (Hb ≤110g/L, Ret-He <29.6 pg, zinc protoporphyrin >75 mol/mol hem participated in the study. After iron supplementation, reticulocyte counts increased from 0.061±0.015x1012/L to 0.079±0.026x1012/L and Ret-He increased from 23.6±2.8 pg to 28.3±2.6 pg (P=<0.001. RBC-He increased from 26.9±1.9 pg to 27.4±1.8 pg (not significant, NS and Ret-He/RBC-He ratio increased from 0.97±0.06 towards 1.07±0.05 (P=<0.001. Hb concentrations demonstrated an obvious increase from 105±6 g/L towards 115±5 g/L (P≤0.001 after supplementation. An obvious increase in RBC distribution width was observed from 45.0±3.6 fL towards 52.3±7.0 fL (P≤0.001. We recommend that Ret-He and Ret-He/RBC-He ratio be integrated into the protocols for anemia screening and for monitoring effects of iron supplementation during pregnancy. In particular, the parameters should be considered in subjects with Hb results in the controversial range of 101-108 g/L.

  12. Converting sunlight into red light in fluorosilicate glass for amorphous silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Chengguo, E-mail: mingchengguo1978@163.com [Physics Department, School of Sciences, Tianjin University of Science & Technology, Tianjin 300457 (China); Song, Feng [Photonics Center, College of Physical Science, Nankai University, Tianjin 300071 (China); Ren, Xiaobin [Physics Department, School of Sciences, Tianjin University of Science & Technology, Tianjin 300457 (China); Yuan, Fengying; Qin, Yueting [Physics Department, School of Sciences, Tianjin University of Science & Technology, Tianjin 300457 (China); Photonics Center, College of Physical Science, Nankai University, Tianjin 300071 (China); An, Liqun; Cai, Yuanxue [Physics Department, School of Sciences, Tianjin University of Science & Technology, Tianjin 300457 (China)

    2017-03-15

    Fluorosilicate glass was prepared by high-temperature melting method to explore highly efficient luminescence materials for amorphous silicon solar cells. Absorption, excitation and emission spectra of the glass were measured. The optical characters of the glass were discussed in details. The glass can efficiently convert sunlight into red light. Our glass can be applied to amorphous silicon solar cells as a converter of solar spectrum.

  13. The Effect of Disinfection on Viability and Function of Baboon Red Blood Cells and Platelets

    Science.gov (United States)

    1997-07-11

    blood cells was evaluated by their ability to transport oxygen as assessed by measurement of 2,3 diphosphoglycerate (DPG)14 and red blood cell p50,15...Blood collected from the bleeding time site (referred to as "shed blood") had a significantly reduced thromboxane A2 level . The ability of the...preserved or treated platelets to increase the shed blood thromboxane A2 level and reduce the 8; extended bleeding time is the measure of their

  14. Men with Sickle Cell Anemia and Priapism Exhibit Increased Hemolytic Rate, Decreased Red Blood Cell Deformability and Increased Red Blood Cell Aggregate Strength.

    Directory of Open Access Journals (Sweden)

    Kizzy-Clara Cita

    Full Text Available To investigate the association between priapism in men with sickle cell anemia (SCA and hemorheological and hemolytical parameters.Fifty-eight men with SCA (median age: 38 years were included; 28 who had experienced priapism at least once during their life (priapism group and 30 who never experienced this complication (control group. Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC deformability at 30 Pa (ektacytometry and RBC aggregation properties (laser backscatter versus time. Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH, aspartate aminotransferase (ASAT, total bilirubin (BIL levels and reticulocyte (RET percentage to calculate a hemolytic index.Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01, LDH (p = 0.03, RET (p = 0.03 levels and hemolytic indices (p = 0.02. Higher RBC aggregates strength (p = 0.01 and lower RBC deformability (p = 0.005 were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01 and RBC aggregate strength (p = 0.03 were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01 than controls.Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.

  15. Light spectrum regulates cell accumulation during daytime in the raphidophyte Chattonella antiqua causing noxious red tides.

    Science.gov (United States)

    Shikata, Tomoyuki; Matsunaga, Shigeru; Kuwahara, Yusuke; Iwahori, Sho; Nishiyama, Yoshitaka

    2016-07-01

    Most marine raphidophyte species cause noxious red tides in temperate coastal areas around the world. It is known that swimming abilities enable raphidophytes to accumulation of cells and to actively acquire light at surface layers and nutrients over a wide depth range. However, it remains unclear how the swimming behavior is affected by environmental conditions, especially light condition. In the present study, we observed the accumulation of the harmful red-tide raphidophyte Chattonella antiqua under various light conditions during the daytime in the laboratory. When exposed to ultraviolet-A/blue light (320-480nm) or red light (640-680nm) from above, cells moved downward. In the case of blue light (455nm), cells started to swim downward after 5-15min of irradiation at a photon flux density≥10μmolm(-2)s(-1). When exposed to monochromatic lights (400-680nm) from the side, cells moved away from the blue light source and then descended, but just moved downward under red light. However, mixing of green/orange light (520-630nm) diminished the effects of blue light. When exposed to a mixture of 30μmolm(-2)s(-1) of blue light (440nm) and ≥6μmolm(-2)s(-1) of yellow light (560nm) from above, cells did not move downward. These results indicate that blue light induces negative phototaxis and ultraviolet-A/blue and red lights induce descending, and green/orange light cancels out their effects in C. antiqua. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Cholestasis in neonates with red cell alloimmune hemolytic disease: incidence, risk factors and outcome.

    Science.gov (United States)

    Smits-Wintjens, Vivianne E H J; Rath, Mirjam E A; Lindenburg, Irene T M; Oepkes, Dick; van Zwet, Erik W; Walther, Frans J; Lopriore, Enrico

    2012-01-01

    Etiology of cholestatic liver disease in neonates with hemolytic disease of the newborn (HDN) has been associated with iron overload due to intrauterine red cell transfusions (IUTs). Data on the incidence and severity of cholestasis in neonates with HDN are scarce, and little is known about pathogenesis, risk factors, neonatal management and outcome. To evaluate incidence, risk factors, management and outcome of cholestasis in neonates with red cell alloimmune hemolytic disease. All (near-) term neonates with HDN due to red cell alloimmunization admitted to our center between January 2000 and July 2010 were included in this observational study. Liver function tests (including conjugated bilirubin) were routinely performed in the neonatal period. We recorded the presence of cholestasis, investigated several potential risk factors and evaluated the management and outcome in affected neonates. A total of 313 infants with red cell alloimmune hemolytic disease treated with or without IUTs were included. The incidence of cholestasis was 13% (41/313). Two risk factors were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70-19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05-20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was started, and one neonate required iron chelation therapy. Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization. Copyright © 2012 S. Karger AG, Basel.

  17. Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

    Science.gov (United States)

    Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

    2018-03-01

    Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

  18. Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

    Science.gov (United States)

    Moriya, Nobuki; Miyazaki, Mitsunori

    2018-02-14

    Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

  19. Endo-lysosomal dysfunction in human proximal tubular epithelial cells deficient for lysosomal cystine transporter cystinosin.

    Directory of Open Access Journals (Sweden)

    Ekaterina A Ivanova

    Full Text Available Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. Early manifestations of the disease include renal Fanconi syndrome, a generalized proximal tubular dysfunction. Current therapy of cystinosis is based on cystine-lowering drug cysteamine that postpones the disease progression but offers no cure for the Fanconi syndrome. We studied the mechanisms of impaired reabsorption in human proximal tubular epithelial cells (PTEC deficient for cystinosin and investigated the endo-lysosomal compartments of cystinosin-deficient PTEC by means of light and electron microscopy. We demonstrate that cystinosin-deficient cells had abnormal shape and distribution of the endo-lysosomal compartments and impaired endocytosis, with decreased surface expression of multiligand receptors and delayed lysosomal cargo processing. Treatment with cysteamine improved surface expression and lysosomal cargo processing but did not lead to a complete restoration and had no effect on the abnormal morphology of endo-lysosomal compartments. The obtained results improve our understanding of the mechanism of proximal tubular dysfunction in cystinosis and indicate that impaired protein reabsorption can, at least partially, be explained by abnormal trafficking of endosomal vesicles.

  20. Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2

    Science.gov (United States)

    Fedier, A; Ruefenacht, U B; Schwarz, V A; Haller, U; Fink, D

    2002-01-01

    A large fraction of human tumours carries mutations in the p53 gene. p53 plays a central role in controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack of p53 function impairs these cellular processes, and this may be the basis of resistance to chemotherapeutic regimens. By virtue of the involvement of DNA mismatch repair in modulating cytotoxic pathways in response to DNA damaging agents, we investigated the effects of loss of Pms2 on the sensitivity to a panel of widely used anticancer agents in E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient in Pms2. We report that lack of the Pms2 gene is associated with an increased sensitivity, ranging from 2–6-fold, to some types of anticancer agents including the topoisomerase II poisons doxorubicin, etoposide and mitoxantrone, the platinum compounds cisplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, and the antimetabolite gemcitabine. In contrast, no change in sensitivity was found after treatment with 5-fluorouracil. Cell cycle analysis revealed that both, Pms2-deficient and -proficient cells, retain the ability to arrest at the G2/M upon cisplatin treatment. The data indicate that the concomitant loss of Pms2 function chemosensitises p53-deficient cells to some types of anticancer agents, that Pms2 positively modulates cell survival by mechanisms independent of p53, and that increased cytotoxicity is paralleled by increased apoptosis. Tumour-targeted functional inhibition of Pms2 may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers. British Journal of Cancer (2002) 87, 1027–1033. doi:10.1038/sj.bjc.6600599 www.bjcancer.com © 2002 Cancer Research UK PMID:12434296

  1. Morphological changes of the red blood cells treated with metal oxide nanoparticles.

    Science.gov (United States)

    Kozelskaya, A I; Panin, A V; Khlusov, I A; Mokrushnikov, P V; Zaitsev, B N; Kuzmenko, D I; Vasyukov, G Yu

    2016-12-01

    The toxic effect of Al 2 O 3 , SiО 2 and ZrО 2 nanoparticles on red blood cells of Wistar rats was studied in vitro using the atomic force microscopy and the fluorescence analysis. Transformation of discocytes into echinocytes and spherocytes caused by the metal oxide nanoparticles was revealed. It was shown that only extremely high concentration of the nanoparticles (2mg/ml) allows correct estimating of their effect on the cell morphology. Besides, it was found out that the microviscosity changes of red blood cell membranes treated with nanoparticles began long before morphological modifications of the cells. On the contrary, the negatively charged ZrO 2 and SiO 2 nanoparticles did not affect ghost microviscosity up to concentrations of 1μg/ml and 0.1mg/ml, correspondingly. In its turn, the positively charged Al 2 O 3 nanoparticles induced structural changes in the lipid bilayer of the red blood cells already at a concentration of 0.05μg/ml. A decrease in microviscosity of the erythrocyte ghosts treated with Al 2 O 3 and SiO 2 nanoparticles was shown. It was detected that the interaction of ZrO 2 nanoparticles with the cells led to an increase in the membrane microviscosity and cracking of swollen erythrocytes. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Structural damage of chicken red blood cells exposed to platinum nanoparticles and cisplatin

    DEFF Research Database (Denmark)

    Kutwin, Marta; Sawosz, Ewa; Jaworski, Sławomir

    2014-01-01

    of platinum nanoparticles (NP-Pt) and cisplatin with blood compartments are important for future applications. This study investigated structural damage, cell membrane deformation and haemolysis of chicken embryo red blood cells (RBC) after treatment with cisplatin and NP-Pt. Cisplatin (4 μg/ml) and NP-Pt (2......,6 μg/ml), when incubated with chicken embryo RBC, were detrimental to cell structure and induced haemolysis. The level of haemolytic injury was increased after cisplatin and NP-Pt treatments compared to the control group. Treatment with cisplatin caused structural damage to cell membranes...

  3. [Epididymis in an experimental model of DHT deficiency: immunolocalization of ERalpha and ERbeta in rat epididymal epithelial cells. In vivo and in vitro studies].

    Science.gov (United States)

    Kolasa, Agnieszka

    2006-01-01

    The aim of this study was to determine the effect of reduced availability of dihydrotestosterone (DHT) on the expression of estrogen receptors alpha and beta (ERalpha and ERbeta) in the epididymis in vivo and in vitro. Expression of estrogen receptors (ERs) is interesting because of the fact that the male reproductive system is controlled not only by androgens but also, in a far-reaching and complex manner, by estrogens. Control by estrogens is exercised through activation of ERs widely distributed in the epididymal epithelium. Epididymal epithelial cells contain a 5alpha-reductase (5alpha-red) which catalyzes the irreversible conversion of testosterone (T) into the most potent and chief androgen of the epididymis, dihydrotestosterone, known to maintain and regulate the structure and functions of the epididymis. Two isoforms of the 5alpha-red were identified: type 1 (5alpha-redl) and type 2 (5alpha-red2). 5alpha-reductase type 2 is more widely expressed in the epididymis than 5alpha-redl. DHT deficit was produced by inhibition of 5alpha-red2 using finasteride (Proscar, MSD Sweden), a steroid inhibitor of this enzyme. The study was performed in the adult, male Wistar rats randomly divided into control (K) and study (Fin56) groups (5 animals in each). Animals in the study group received 5mg finasteride/kg b.w., orally during 56 days (duration of one spermatogenesis). Immunoexpression of ERs was also studied in epididymal epithelial cells cultured with or without finasteride. It was shown that DHT deficiency, both in vivo and in vitro condition, modulated ERs expression in comparison to the epididymis from control rats and to epididymal cells cultured without finasteride. Distribution of ERalpha and ERbeta in epididymal cells changed (from nucleus to cytoplasm) and the level of ERs expression was markedly decreased. The present findings show that the DHT deficiency caused by finasteride altered the expression of ERalpha and ERbeta in the epididymis and possibly may

  4. Direct Cytoskeleton Forces Cause Membrane Softening in Red Blood Cells

    Science.gov (United States)

    Rodríguez-García, Ruddi; López-Montero, Iván; Mell, Michael; Egea, Gustavo; Gov, Nir S.; Monroy, Francisco

    2015-01-01

    Erythrocytes are flexible cells specialized in the systemic transport of oxygen in vertebrates. This physiological function is connected to their outstanding ability to deform in passing through narrow capillaries. In recent years, there has been an influx of experimental evidence of enhanced cell-shape fluctuations related to metabolically driven activity of the erythroid membrane skeleton. However, no direct observation of the active cytoskeleton forces has yet been reported to our knowledge. Here, we show experimental evidence of the presence of temporally correlated forces superposed over the thermal fluctuations of the erythrocyte membrane. These forces are ATP-dependent and drive enhanced flickering motions in human erythrocytes. Theoretical analyses provide support for a direct force exerted on the membrane by the cytoskeleton nodes as pulses of well-defined average duration. In addition, such metabolically regulated active forces cause global membrane softening, a mechanical attribute related to the functional erythroid deformability. PMID:26083919

  5. Effects of He-Ne laser irradiation on red blood cells in vitro

    Science.gov (United States)

    Ghadage, Vijay H.; Kulkarni, Gauri R.

    2011-03-01

    Laser radiation has many applications in biomedical field, such as wound healing, tissue repairing, heating and ablation processes. Intravenous low power laser radiation is used clinically for skin and vascular disorders. Laser radiation improves microcirculation and modulates the rheological properties of blood. FTIR (Fourier Transform Infra Red Spectra) is used to see the structural changes in erythrocyte membrane. In the present work He Ne laser (λ= 632nm, power=2mW) is used to irradiate human Red blood cells. Red blood cells are separated from human whole blood using centrifugation method (time=10 min., temperature=15°C and RPM=3000) and then exposed to HeNe laser radiation. Laser exposure time is varied from 10 min. to 40min for Red blood cells. Absorption spectrum, FTIR and fluorescence spectra of RBC are compared before and after HeNe laser irradiation. The absorption spectrum of RBC after exposure to HeNe laser shows a significant decrease in absorbance. The FTIR spectrum of non irradiated RBC clearly show the peaks due to O-H (free group), C=O (amide I group), N=O (nitro group), C-O (anhydride group) and C-H (aromatic group). Laser radiation changes in transmittance in FTIR spectra related to C=O group and percentage of transmittance increases for O-H, C=C, N=O, C-O and C-H group.

  6. Assessment of oxidant susceptibility of red blood cells in various species based on cell deformability.

    Science.gov (United States)

    Simmonds, Michael J; Meiselman, Herbert J; Marshall-Gradisnik, Sonya M; Pyne, Michael; Kakanis, Michael; Keane, James; Brenu, Ekua; Christy, Rhys; Baskurt, Oguz K

    2011-01-01

    The present study was designed to investigate the oxidant susceptibility of red blood cells (RBC) from four species (echidna, human, koala, Tasmanian devil) based on changes in cellular deformability. These species were specifically chosen based on differences in lifestyle and/or biology associated with varied levels of oxidative stress. The major focus was the influence of superoxide radicals generated within the cell (phenazine methosulfate, PMS, 50 μM) or in the extracellular medium (xanthine oxidase-hypoxanthine, XO-HX, 0.1 U/ml XO) on RBC deformability at various shear stresses (SS). RBC deformability was assessed by laser-diffraction analysis using a "slit-flow ektacytometer". Both superoxide-generating treatments resulted in significant increases of methemoglobin for all species (p koala cells exhibited a similar sigmoid-like response to SS, short-beaked echidna values were markedly lower and only increased slightly with SS, while Tasmanian devil RBC were extremely rigid. The effect of XO-HX on RBC deformability was less when compared with PMS (i.e., smaller increase in rigidity) with the exception of Tasmanian devil RBC which exhibited essentially no deformation even at the highest SS; Tasmanian devil RBC response to XO-HX was thus comparable to that observed with PMS. Our findings indicate that ektacytometry can be used to determine the oxidant susceptibility of RBC from different species which varies significantly among mammals representing diverse lifestyles and evolutionary histories. These differences in susceptibility are consistent with species-specific discrepancies between observed and allometrically-predicted life spans and are compatible with the oxidant theory of aging.

  7. Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann cells.

    Science.gov (United States)

    Petrilli, Alejandra M; Garcia, Jeanine; Bott, Marga; Klingeman Plati, Stephani; Dinh, Christine T; Bracho, Olena R; Yan, Denise; Zou, Bing; Mittal, Rahul; Telischi, Fred F; Liu, Xue-Zhong; Chang, Long-Sheng; Welling, D Bradley; Copik, Alicja J; Fernández-Valle, Cristina

    2017-05-09

    Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC). Merlin-deficient HSC had higher levels of phosphorylated PDGFRα/β, and SRC than merlin-expressing HSC. A similar phosphorylation pattern was observed in phospho-protein arrays of human vestibular schwannoma samples compared to normal HSC. Ponatinib reduced merlin-deficient HSC viability in a dose-dependent manner by decreasing phosphorylation of PDGFRα/β, AKT, p70S6K, MEK1/2, ERK1/2 and STAT3. These changes were associated with decreased cyclin D1 and increased p27Kip1levels, leading to a G1 cell-cycle arrest as assessed by Western blotting and flow cytometry. Ponatinib did not modulate ABL, SRC, focal adhesion kinase (FAK), or paxillin phosphorylation levels. These results suggest that ponatinib is a potential therapeutic agent for NF2-associated schwannomas and warrants further in vivo investigation.

  8. Failure of lysosome clustering and positioning in the juxtanuclear region in cells deficient in rapsyn

    Science.gov (United States)

    Aittaleb, Mohamed; Chen, Po-Ju; Akaaboune, Mohammed

    2015-01-01

    ABSTRACT Rapsyn, a scaffold protein, is required for the clustering of acetylcholine receptors (AChRs) at contacts between motor neurons and differentiating muscle cells. Rapsyn is also expressed in cells that do not express AChRs. However, its function in these cells remains unknown. Here, we show that rapsyn plays an AChR-independent role in organizing the distribution and mobility of lysosomes. In cells devoid of AChRs, rapsyn selectively induces the clustering of lysosomes at high density in the juxtanuclear region without affecting the distribution of other intracellular organelles. However, when the same cells overexpress AChRs, rapsyn is recruited away from lysosomes to colocalize with AChR clusters on the cell surface. In rapsyn-deficient (Rapsn−/−) myoblasts or cells overexpressing rapsyn mutants, lysosomes are scattered within the cell and highly dynamic. The increased mobility of lysosomes in Rapsn−/− cells is associated with a significant increase in lysosomal exocytosis, as evidenced by increased release of lysosomal enzymes and plasma membrane damage when cells were challenged with the bacterial pore-forming toxin streptolysin-O. These findings uncover a new link between rapsyn, lysosome positioning, exocytosis and plasma membrane integrity. PMID:26330529

  9. Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson disease.

    Science.gov (United States)

    Magalhaes, Joana; Gegg, Matthew E; Migdalska-Richards, Anna; Doherty, Mary K; Whitfield, Phillip D; Schapira, Anthony H V

    2016-08-15

    Glucocerebrosidase (GBA1) gene mutations increase the risk of Parkinson disease (PD). While the cellular mechanisms associating GBA1 mutations and PD are unknown, loss of the glucocerebrosidase enzyme (GCase) activity, inhibition of autophagy and increased α-synuclein levels have been implicated. Here we show that autophagy lysosomal reformation (ALR) is compromised in cells lacking functional GCase. ALR is a cellular process controlled by mTOR which regenerates functional lysosomes from autolysosomes formed during macroautophagy. A decrease in phopho-S6K levels, a marker of mTOR activity, was observed in models of GCase deficiency, including primary mouse neurons and the PD patient derived fibroblasts with GBA1 mutations, suggesting that ALR is compromised. Importantly Rab7, a GTPase crucial for endosome-lysosome trafficking and ALR, accumulated in GCase deficient cells, supporting the notion that lysosomal recycling is impaired. Recombinant GCase treatment reversed ALR inhibition and lysosomal dysfunction. Moreover, ALR dysfunction was accompanied by impairment of macroautophagy and chaperone-mediated autophagy, increased levels of total and phosphorylated (S129) monomeric α-synuclein, evidence of amyloid oligomers and increased α-synuclein release. Concurrently, we found increased cholesterol and altered glucosylceramide homeostasis which could compromise ALR. We propose that GCase deficiency in PD inhibits lysosomal recycling. Consequently neurons are unable to maintain the pool of mature and functional lysosomes required for the autophagic clearance of α-synuclein, leading to the accumulation and spread of pathogenic α-synuclein species in the brain. Since GCase deficiency and lysosomal dysfunction occur with ageing and sporadic PD pathology, the decrease in lysosomal reformation may be a common feature in PD. © The Author 2016. Published by Oxford University Press.

  10. A case of multiple squamous cell carcinomas arising from red tattoo pigment

    Directory of Open Access Journals (Sweden)

    E. Maxim, BS, MS

    2017-12-01

    Full Text Available Ornamental tattooing involves the administration of exogenous pigments into the skin to create a permanent design. Our case focuses on a 62-year-old woman who presented with an inflamed enlarging nodule on her right proximal calf, which arose within the red pigment of an ornamental tattoo. The nodule was diagnosed as squamous cell carcinoma (SCC and subsequently excised. Over the course of the following year, the patient was diagnosed with a total of five additional SCCs that also arose within the red pigment of the tattoo. The increased popularity of tattooing and the lack of industry safety standards for tattoo ink production, especially metal-laden red pigments, may lead to more cases of skin cancer arising within tattoos among patients of all ages.

  11. Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis.

    Directory of Open Access Journals (Sweden)

    Fei Cheng

    Full Text Available Clinical and experimental evidence suggests a protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx-1 in the atherogenic process. GPx-1 deficiency accelerates atherosclerosis and increases lesion cellularity in ApoE(-/- mice. However, the distribution of GPx-1 within the atherosclerotic lesion as well as the mechanisms leading to increased macrophage numbers in lesions is still unknown. Accordingly, the aims of the present study were (1 to analyze which cells express GPx-1 within atherosclerotic lesions and (2 to determine whether a lack of GPx-1 affects macrophage foam cell formation and cellular proliferation. Both in situ-hybridization and immunohistochemistry of lesions of the aortic sinus of ApoE(-/- mice after 12 weeks on a Western type diet revealed that both macrophages and - even though to a less extent - smooth muscle cells contribute to GPx-1 expression within atherosclerotic lesions. In isolated mouse peritoneal macrophages differentiated for 3 days with macrophage-colony-stimulating factor (MCSF, GPx-1 deficiency increased oxidized low density-lipoprotein (oxLDL induced foam cell formation and led to increased proliferative activity of peritoneal macrophages. The MCSF- and oxLDL-induced proliferation of peritoneal macrophages from GPx-1(-/-ApoE(-/- mice was mediated by the p44/42 MAPK (p44/42 mitogen-activated protein kinase, namely ERK1/2 (extracellular-signal regulated kinase 1/2, signaling pathway as demonstrated by ERK1/2 signaling pathways inhibitors, Western blots on cell lysates with primary antibodies against total and phosphorylated ERK1/2, MEK1/2 (mitogen-activated protein kinase kinase 1/2, p90RSK (p90 ribosomal s6 kinase, p38 MAPK and SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase, and immunohistochemistry of mice atherosclerotic lesions with antibodies against phosphorylated ERK1/2, MEK1/2 and p90RSK. Representative effects of GPx-1 deficiency on both macrophage proliferation and

  12. Minimal volume regulation after shrinkage of red blood cells from five species of reptiles

    DEFF Research Database (Denmark)

    Kristensen, Karina; Berenbrink, Michael; Koldkjær, Pia

    2008-01-01

    Red blood cells (RBCs) from most vertebrates restore volume upon hypertonic shrinkage and the mechanisms underlying this regulatory volume increase (RVI) have been studied extensively in these cells. Despite the phylogenetically interesting position of reptiles, very little is known about their red...... cell function. The present study demonstrates that oxygenated RBCs in all major groups of reptiles exhibit no or a very reduced RVI upon ~ 25% calculated hyperosmotic shrinkage. Thus, RBCs from the snakes Crotalus durissus and Python regius, the turtle Trachemys scripta and the alligator Alligator...... was not characterized. It seems, therefore, that the RVI response based on NHE activation was lost among the early sauropsids that gave rise to modern reptiles and birds, while it was retained in mammals. An RVI response has then reappeared in birds, but based on activation of the NKCC. Alternatively, the absence...

  13. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis.

    Science.gov (United States)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-11-01

    The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs) in pancreatitis. We analyzed changes in LAMPs in experimental models and human pancreatitis, and the underlying mechanisms: LAMP de-glycosylation and degradation. LAMP cleavage by cathepsin B (CatB) was analyzed by mass spectrometry. We used mice deficient in LAMP-2 to assess its role in pancreatitis. Pancreatic levels of LAMP-1 and LAMP-2 greatly decrease across various pancreatitis models and in human disease. Pancreatitis does not trigger LAMPs' bulk de-glycosylation, but induces their degradation via CatB-mediated cleavage of LAMP molecule close to the boundary between luminal and transmembrane domains. LAMP-2 null mice spontaneously develop pancreatitis that begins with acinar cell vacuolization due to impaired autophagic flux, and progresses to severe pancreas damage characterized by trypsinogen activation, macrophage-driven inflammation, and acinar cell death. LAMP-2 deficiency causes a decrease in pancreatic digestive enzymes content, stimulates the basal and inhibits CCK-induced amylase secretion by acinar cells. The effects of LAMP-2 knockout and acute cerulein pancreatitis overlap, which corroborates the pathogenic role of LAMP decrease in experimental pancreatitis models. The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis, and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice with LAMP-2 deficiency present a novel genetic model of human pancreatitis caused by lysosomal/autophagic dysfunction.

  14. Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

    Science.gov (United States)

    Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

    2012-09-01

    UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

  15. The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

    Science.gov (United States)

    Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

    2000-05-25

    DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

  16. A Gaussian process and derivative spectral-based algorithm for red blood cell segmentation

    Science.gov (United States)

    Xue, Yingying; Wang, Jianbiao; Zhou, Mei; Hou, Xiyue; Li, Qingli; Liu, Hongying; Wang, Yiting

    2017-07-01

    As an imaging technology used in remote sensing, hyperspectral imaging can provide more information than traditional optical imaging of blood cells. In this paper, an AOTF based microscopic hyperspectral imaging system is used to capture hyperspectral images of blood cells. In order to achieve the segmentation of red blood cells, Gaussian process using squared exponential kernel function is applied first after the data preprocessing to make the preliminary segmentation. The derivative spectrum with spectral angle mapping algorithm is then applied to the original image to segment the boundary of cells, and using the boundary to cut out cells obtained from the Gaussian process to separated adjacent cells. Then the morphological processing method including closing, erosion and dilation is applied so as to keep adjacent cells apart, and by applying median filtering to remove noise points and filling holes inside the cell, the final segmentation result can be obtained. The experimental results show that this method appears better segmentation effect on human red blood cells.

  17. Intracellular vesicles as reproduction elements in cell wall-deficient L-form bacteria.

    Science.gov (United States)

    Briers, Yves; Staubli, Titu; Schmid, Markus C; Wagner, Michael; Schuppler, Markus; Loessner, Martin J

    2012-01-01

    Cell wall-deficient bacteria, or L-forms, represent an extreme example of bacterial plasticity. Stable L-forms can multiply and propagate indefinitely in the absence of a cell wall. Data presented here are consistent with the model that intracellular vesicles in Listeria monocytogenes L-form cells represent the actual viable reproductive elements. First, small intracellular vesicles are formed along the mother cell cytoplasmic membrane, originating from local phospholipid accumulation. During growth, daughter vesicles incorporate a small volume of the cellular cytoplasm, and accumulate within volume-expanding mother cells. Confocal Raman microspectroscopy demonstrated the presence of nucleic acids and proteins in all intracellular vesicles, but only a fraction of which reveals metabolic activity. Following collapse of the mother cell and release of the daughter vesicles, they can establish their own membrane potential required for respiratory and metabolic processes. Premature depolarization of the surrounding membrane promotes activation of daughter cell metabolism prior to release. Based on genome resequencing of L-forms and comparison to the parental strain, we found no evidence for predisposing mutations that might be required for L-form transition. Further investigations revealed that propagation by intracellular budding not only occurs in Listeria species, but also in L-form cells generated from different Enterococcus species. From a more general viewpoint, this type of multiplication mechanism seems reminiscent of the physicochemical self-reproducing properties of abiotic lipid vesicles used to study the primordial reproduction pathways of putative prokaryotic precursor cells.

  18. Loss of Acetylcholine Signaling Reduces Cell Clearance Deficiencies in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Sérgio M Pinto

    Full Text Available The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole-sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the "eat-me" signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency.