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Sample records for cell transfusion independence

  1. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Maha A. Badawi

    2010-01-01

    Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

  2. Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

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    Harpreet Kochhar

    2015-01-01

    Full Text Available Background. Hematologic improvement (HI occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT but there is little information on transfusion status after stopping chelation. Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient’s course in detail and review the literature on HI with chelation. Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.

  3. Transfusion of platelets, but not of red blood cells, is independently associated with nosocomial infections in the critically ill

    NARCIS (Netherlands)

    Engele, Leo J.; Straat, Marleen; van Rooijen, Ingeborg H M; de Vooght, Karen M K; Cremer, Olaf L.; Schultz, Marcus J.; Bos, Lieuwe D J; Juffermans, Nicole P.

    2016-01-01

    Background: Red blood cell (RBC) transfusion has been associated with nosocomial infection in the critically ill patients. However, this association may be confounded by length of stay, as prolonged intensive care unit (ICU stay) increases both risk of infection and risk of transfusion. Also, it is

  4. 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...

  5. Allogeneic hematopoietic stem cell transplantation: transfusion issues

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    Akkök ÇA

    2016-05-01

    Full Text Available Çiğdem Akalın Akkök,1,21Department of Immunology and Transfusion Medicine, Oslo University Hospital, Ullevaal, Oslo, Norway; 2Department of Clinical Immunology and Transfusion Medicine, Lund University Hospital, Lund, Sweden Abstract: Allogeneic hematopoietic stem cell transplantation (AHSCT is an intention-to-cure treatment strategy in several malignancies and nonmalignancies. The number of patients receiving AHSCT is increasing due to new indications, and more elderly patients with comorbidities are included in the protocols. Survival of the patients undergoing AHSCT has improved owing to better patient care, including optimization of transfusion support, which has a major contribution. However, transfusion can also be hazardous. Increasing awareness about transfusion and finding the balance between avoiding unnecessary transfusions and transfusing the correct component when needed are the key issues. Myeloablative conditioning results in pancytopenia, and the patients are prone to infections, anemia, and bleeding both before and after transplantation. Until red cell and platelet engraftment, the patients are usually transfusion dependent needing red cell and/or platelet components. Physicians dealing with AHSCT patients should be well informed about the attributes of the blood components they order. Knowledge about transfusion indications, triggers, and how to prevent and manage eventual transfusion complications is also required. The clinical picture can be challenging, and transplantation/treatment-related toxicity/complications can sometimes be difficult to distinguish from a transfusion complication, especially if the latter one took place, for instance, several days or weeks ago. ABO compatibility between the patient and the donor is not a prerequisite when choosing human leukocyte antigen-matched hematopoietic stem cell donor. Consequently, ABO incompatibility exists in ~40% of the cases and brings some immunohematological issues

  6. Red blood cell alloimmunization after blood transfusion

    NARCIS (Netherlands)

    Schonewille, Henk

    2008-01-01

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

  7. 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

    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...

  8. 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....

  9. Neurological Complications following Blood Transfusions in Sickle Cell Anemia

    Science.gov (United States)

    Khawar, Nayaab; Kulpa, Jolanta; Bellin, Anne; Proteasa, Simona; Sundaram, Revathy

    2017-01-01

    In Sickle Cell Anemia (SCA) patient blood transfusions are an important part of treatment for stroke and its prevention. However, blood transfusions can also lead to complications such as Reversible Posterior Leukoencephalopathy Syndrome (RPLS). This brief report highlights two cases of SCA who developed such neurological complications after a blood transfusion. RLPS should be considered as the cause of neurologic finding in patients with SCA and hypertension following a blood transfusion.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  11. Transfusion of Leukocyte-Depleted RBCs Is Independently Associated With Increased Morbidity After Pediatric Cardiac Surgery

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; Grotenhuis, Femke; Berger, Rolf F. M.; Ebels, Tjark W.; Burgerhof, Johannes G. M.; Albers, Marcel J. I. J.

    2013-01-01

    Objective: To test the hypothesis that transfusion of leukocyte-depleted RBC preparations within the first 48 hours of PICU stay was independently associated with prolonged duration of mechanical ventilation, irrespective of surgery type and disease severity. Design: Retrospective, observational stu

  12. Unique risks of red blood cell transfusions in very-low-birth-weight neonates: associations between early transfusion and intraventricular hemorrhage and between late transfusion and necrotizing enterocolitis.

    Science.gov (United States)

    Christensen, Robert D; Baer, Vickie L; Del Vecchio, Antonio; Henry, Erick

    2013-10-01

    Red blood cell transfusions can be life-saving for neonates with severe anemia or active hemorrhage. However, risks of transfusions exist and should always be weighed against potential benefits. At least two transfusion risks are unique to very low birth weight neonates. The first is an association between transfusions given in the first days after birth and the subsequent occurrence of a grade 3 or 4 intraventricular hemorrhage. The second is an association between "late" RBC transfusions and the subsequent occurrence of necrotizing enterocolitis. Much remains to be discovered about the pathogenesis of these two outcomes. Moreover, work is needed to clearly establish whether transfusions are causatively-associated with these outcomes or are co-variables. This review will provide basic data establishing these associations and propose mechanistic explanations.

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

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    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

  14. No early effect of storage time of transfused red blood cells on fatigue and plasma cytokines in patients with anaemia from non-acute gastrointestinal bleeding

    DEFF Research Database (Denmark)

    Mynster, Tommie; Dziegiel, Morten H; Kofoed, Kristian

    2007-01-01

    Background: Fatigue in anaemia is empirically reduced by blood transfusion. Long storage time of red cells may be associated with immunomodulatory effects, and blood stored for a long time may cause tissue hypoxia upon transfusion. Patients and Methods: 22 patients admitted with haemoglobin ... (nsSL). Beside increase in haemoglobin the only significant change in blood parameters after transfusion was a decrease in thrombocyte count (nsSL). No significant differences were seen in concentrations of cytokines before and after transfusion. Conclusion: Transfusion of two units of red cells...... relieved self-estimated fatigue, independent of blood storage time. Thrombocyte count decreased after transfusion, probably due to dilution by transfused blood. Aged red cells may not, or only sparsely, directly trigger the interleukin cascade....

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

    Institute of Scientific and Technical Information of China (English)

    Chong Lei; Li-Ze Xiong

    2015-01-01

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

  16. Best practices for transfusion for patients with sickle cell disease

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    Ted Wun

    2010-01-01

    Full Text Available The beta-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research.  A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.

  17. Unexpected Anemia and Reticulocytopenia in an Adolescent With Sickle Cell Anemia Receiving Chronic Transfusion Therapy.

    Science.gov (United States)

    Blauel, Emily R; Grossmann, Lily T; Vissa, Madhav; Miller, Scott T

    2015-10-01

    In a patient with sickle cell disease receiving chronic transfusion, exacerbation of anemia with reticulocytopenia must prompt consideration of a delayed hemolytic transfusion reaction with hyperhemolysis, as further transfusion may worsen this condition; definitive diagnosis is sometimes difficult. Anemia evolving during parvovirus B19-induced erythroid hypoplasia (transient aplastic crisis) should be attenuated in chronic transfusion patients due to superior survival of transfused over endogenous red blood cells. A 16-year-old with sickle cell disease receiving chronic transfusion of modified intensity (goal to maintain hemoglobin Sanemia with reticulocytopenia was later shown to have had transient aplastic crisis.

  18. Red blood cell transfusion in septic shock

    DEFF Research Database (Denmark)

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

    2014-01-01

    general intensive care units (ICUs) including all adult patients with septic shock in a 5-month period. RESULTS: Ninety-five of the 213 included patients (45%) received median 3 (interquartile range 2-5) RBC units during shock. The median pre-transfusion haemoglobin level was 8.1 (7.4-8.9) g...... Sepsis-related Organ Failure Assessment (SOFA) scores (days 1 and 5), more days in shock (5 (3-10) vs. 2 (2-4), p = 0.0001), more days in ICU (10 (4-19) vs. 4 (2-8), p = 0.0001) and higher 90-day mortality (66 vs. 43%, p = 0.001). The latter association was lost after adjustment for admission category...

  19. Management of sickle cell disease: challenges and risks of transfusion

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    Serjeant GR

    2016-10-01

    Full Text Available Graham R Serjeant Sickle Cell Trust (Jamaica, Kingston, Jamaica Abstract: Homozygous sickle cell (SS disease is associated with rapid red cell destruction and a tendency to block flow in blood vessels. The bone marrow expansion needed to compensate for the rapid red cell destruction increases metabolic demands and folate requirements but also renders the bone marrow prone to suppression by renal impairment and infections especially those with human parvovirus B19. The abnormal red cells also tend to block blood vessels impairing flow in the bone marrow (dactylitis, bone pain crisis, hip necrosis, the spleen (acute splenic sequestration, chronic hypersplenism, loss of the normal filtering system rendering patients prone to overwhelming septicemia, the lungs (pulmonary embolism, acute chest syndrome, and the brain (ischemic stroke, hemorrhage. Transfusion plays a role in addressing all of these pathologies. During the acute lowering of hemoglobin due to acute splenic sequestration and aplastic crisis and the persistent lowering of hemoglobin due to chronic hypersplenism and chronic renal failure, top-up transfusions may help in maintaining oxygen delivery and symptomatic relief. Addressing vaso-occlusion is more complex but best documented in preventing recurrent stroke and primary stroke following detection of cerebral vessel stenosis by transcranial Doppler. Although top-up transfusions have minimal side effects, potentially serious complications arise from chronic transfusion, and there are many unanswered questions on the duration of such therapy and the natural history of the underlying complications. These issues are addressed with the knowledge currently available. Keywords: sickle hemoglobin, HbS, transfusion, oxygen affinity, anemia, vaso-occlusion

  20. Challenges and promises for the development of donor-independent platelet transfusions.

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    Lambert, Michele P; Sullivan, Spencer K; Fuentes, Rudy; French, Deborah L; Poncz, Mortimer

    2013-04-25

    Platelet transfusions are often a life-saving intervention, and the use of platelet transfusions has been increasing. Donor-derived platelet availability can be challenging. Compounding this concern are additional limitations of donor-derived platelets, including variability in product unit quality and quantity, limited shelf life and the risks of product bacterial contamination, other transfusion-transmitted infections, and immunologic reactions. Because of these issues, there has been an effort to develop strategies to generate platelets from exogenously generated precursor cells. If successful, such platelets have the potential to be a safer, more consistent platelet product, while reducing the necessity for human donations. Moreover, ex vivo-generated autologous platelets or precursors may be beneficial for patients who are refractory to allogeneic platelets. For patients with inherited platelet disorders, ex vivo-generated platelets offer the promise of a treatment via the generation of autologous gene-corrected platelets. Theoretically, ex vivo-generated platelets also offer targeted delivery of ectopic proteins to sites of vascular injury. This review summarizes the current, state-of-the-art methodologies in delivering a clinically relevant ex vivo-derived platelet product, and it discusses significant challenges that must be overcome for this approach to become a clinical reality.

  1. A selective tropism of transfused oval cells for liver

    Institute of Scientific and Technical Information of China (English)

    Jian-Zhi Chen; Hai Hong; Jin Xiang; Ling Xue; Guo-Qiang Zhao

    2003-01-01

    AIM: To explore the biological behaviors of hepatic oval cells after transfused into the circulation of experimental animals.METHODS: Oval cells from male SD rat were transfused into the circulation of a female rat which were treated by a 2-AAF/CCl4 program, through caudal vein. Sex-determining gene sry which located on Y chromosome was examined by PCR and in situ hybridization technique in liver, kidney and spleen of the experimental animals, respectively.RESULTS: The results of the cell-transplant experiment showed that the srygene was detectable only in the liver but not in spleen and kidney of the experimental rats, and no signals could be detected in the control animals. It can be also morphologically proved that some exogenous cells had migrated into the parenchyma of the liver and settled there.CONCLUSION: The result means that there are exogenous cells located in the liver of the experimental animal and the localization is specific to the liver. This indicates that some "signal molecules" must exist in the circulation of the rats treated by 2-AAF/CCl4. These "signal molecules" might play an important role in specific localization and differentiation of transfused oval cells.

  2. Efficiency and Cost Analysis of Cell Saver Auto Transfusion System in Total Knee Arthroplasty

    Science.gov (United States)

    Bilgili, Mustafa Gökhan; Erçin, Ersin; Peker, Gökhan; Kural, Cemal; Başaran, Serdar Hakan; Duramaz, Altuğ; Avkan, Cevdet

    2014-01-01

    Background: Blood loss and replacement is still a controversial issue in major orthopaedic surgery. Allogenic blood transfusion may cause legal problems and concerns regarding the transmission of transfusion-related diseases. Cellsaver Systems (CSS) were developed as an alternative to allogenic transfusion but CSS transfusion may cause coagulation, infection and haemodynamic instability. Aims: Our aim was to analyse the efficiency and cost analysis of a cell saver auto-transfusion system in the total knee arthroplasty procedure. Study Design: Retrospective comparative study. Methods: Those patients who were operated on by unilateral, cemented total knee arthroplasty (TKA) were retrospectively evaluated. Group 1 included 37 patients who were treated using the cell saver system, and Group 2 involved 39 patients who were treated by allogenic blood transfusion. The groups were compared in terms of preoperative haemoglobin and haematocrit levels, blood loss and transfusion amount, whether allogenic transfusion was made, degree of deformity, body mass index and cost. Results: No significant results could be obtained in the statistical comparisons made in terms of the demographic properties, deformity properties, preoperative laboratory values, transfusion amount and length of hospital stay of the groups. Average blood loss was calculated to be less in Group 1 (p<0.05) and cost was higher in Group 1 (p<0.05). Conclusion: Cell saver systems do not decrease the amount of allogenic blood transfusion and costs more. Therefore, the routine usage of the auto-transfusion systems is a controversial issue. Cell saver system usage does not affect allogenic blood transfusion incidence or allogenic blood transfusion volume. It was found that preoperative haemoglobin and body mass index rates may affect allogenic blood transfusion. Therefore, it is foreseen that auto-transfusion systems could be useful in patients with low haemoglobin level and body mass index. PMID:25207187

  3. Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion

    DEFF Research Database (Denmark)

    Halmin, Märit; Rostgaard, Klaus; Lee, Brian K

    2017-01-01

    Background: Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists. Objective: To study the association between...... received transfusions from 2003 to 2012. Measurements: Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox...... proportional hazards regression. Results: Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days...

  4. Successful implementation of a packed red blood cell and fresh frozen plasma transfusion protocol in the surgical intensive care unit.

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    Benjamin E Szpila

    Full Text Available Blood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC and fresh frozen plasma (FFP transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU.We performed a retrospective, historical control analysis comparing before (PRE and after (POST implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression models were developed to determine if implementation of the restrictive transfusion protocol is an independent predictor of adverse outcomes after controlling for age, illness severity, and total blood products received.829 total patients were included in the analysis (PRE, n=372; POST, n=457. Despite higher mean age (56 vs. 52 years, p=0.01 and APACHE II scores (12.5 vs. 11.2, p=0.006, mean units transfused per patient were lower for both packed red blood cells (0.7 vs. 1.2, p=0.03 and fresh frozen plasma (0.3 vs. 1.2, p=0.007 in the POST compared to the PRE cohort, respectively. There was no difference in inpatient mortality between the PRE and POST cohorts (7.5% vs. 9.2%, p=0.39. There was a decreased risk of urinary tract infections (OR 0.47, 95%CI 0.28-0.80 in the POST cohort after controlling for age, illness severity and amount of blood products transfused.Implementation of a restrictive transfusion protocol can effectively reduce blood product utilization in critically ill surgical patients with no increase in morbidity or mortality.

  5. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease

    Science.gov (United States)

    Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Wang, Winfred C

    2017-01-01

    Background Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation. This is an update of a Cochrane Review first published in 2002, and last updated in 2013. Objectives To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). Search methods We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 04 April 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 25 April 2016. Selection criteria Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis Two authors independently assessed trial eligibility and the risk of bias and extracted data. Main results We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease. Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion. Two trials compared the drug

  6. Generation of red blood cells from human embryonic/induced pluripotent stem cells for blood transfusion.

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    Ebihara, Yasuhiro; Ma, Feng; Tsuji, Kohichiro

    2012-06-01

    Red blood cell (RBC) transfusion is necessary for many patients with emergency or hematological disorders. However, to date the supply of RBCs remains labile and dependent on voluntary donations. In addition, the transmission of infectious disease via blood transfusion from unspecified donors remains a risk. Establishing a large quantity of safe RBCs would help to address this issue. Human embryonic stem (hES) cells and the recently established human induced pluripotent stem (hiPS) cells represent potentially unlimited sources of donor-free RBCs for blood transfusion, as they can proliferate indefinitely in vitro. Extensive research has been done to efficiently generate transfusable RBCs from hES/iPS cells. Nevertheless, a number of challenges must be overcome before the clinical usage of hES/iPS cell-derived RBCs can become a reality.

  7. Phase I/II safety study of transfusion of prion-filtered red cell concentrates in transfusion-dependent patients.

    LENUS (Irish Health Repository)

    Cahill, M R

    2010-08-01

    Variant Creutzfeldt-Jakob (vCJD) is a fatal transfusion transmissible prion infection. No test for vCJD in the donor population is currently available. Therefore, prion removal by filtration of red cell concentrate (RCC) is an attractive option for prevention.

  8. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery

    DEFF Research Database (Denmark)

    Jensen, L S; Andersen, A J; Christiansen, P M

    1992-01-01

    The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measured...... before operation and 3, 7 and 30 days after surgery in 60 consecutive patients. Of the patients 104 required blood transfusion; 48 received filtered blood and 56 underwent whole blood transfusion. Postoperative infections developed in 13 patients transfused with whole blood (23 per cent, 95 per cent...... function was significantly (P less than 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery. Udgivelsesdato: 1992-Jun...

  9. Mortality risk is dose-dependent on the number of packed red blood cell transfused after coronary artery bypass graft

    OpenAIRE

    dos Santos, Antônio Alceu; de Sousa, Alexandre Gonçalves; Piotto, Raquel Ferrari; Pedroso, Juan Carlos Montano [UNIFESP

    2013-01-01

    Introduction Transfusions of one or more packed red blood cells is a widely strategy used in cardiac surgery, even after several evidences of increased morbidity and mortality. The world's blood shortage is also already evident. Objective To assess whether the risk of mortality is dose-de>pendent on the number of packed red blood cells transfused after coronary artery bypass graft. Methods Between June 2009 and July 2010, were analyzed 3010 patients: transfused and non-transfused. Transfused ...

  10. A case of delayed hemolytic transfusion reaction in sickle cell disease patient

    Science.gov (United States)

    Dogra, Ashu; Sidhu, Meena

    2016-01-01

    Sickle cell disease (SCD) is autosomal recessive, genetically transmitted hemoglobinopathy responsible for considerable morbidity and mortality. It is prevalent in many parts of India including Central India, where the prevalence in different communities has ranged from 9.4% to 22%. Perioperative management may include transfusion of red blood cells. Hemolytic transfusion reactions can occur, and these can be either acute or delayed. We present a case of delayed hemolytic transfusion reaction in a patient with SCD. PMID:27605854

  11. 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.

  12. 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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  14. 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...

  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...... conditions such as transfusion-related acute lung injury and circulatory overload in patients with heart disease. Knowledge of the clinical signs of transfusion-related complications is important for clinicians in order to provide the best possible treatment....

  16. Outpatient red blood cell transfusion payments among patients on chronic dialysis

    Directory of Open Access Journals (Sweden)

    Gitlin Matthew

    2012-11-01

    Full Text Available Abstract Background Payments for red blood cell (RBC transfusions are separate from US Medicare bundled payments for dialysis-related services and medications. Our objective was to examine the economic burden for payers when chronic dialysis patients receive outpatient RBC transfusions. Methods Using Truven Health MarketScan® data (1/1/02-10/31/10 in this retrospective micro-costing economic analysis, we analyzed data from chronic dialysis patients who underwent at least 1 outpatient RBC transfusion who had at least 6 months of continuous enrollment prior to initial dialysis claim and at least 30 days post-transfusion follow-up. A conceptual model of transfusion-associated resource use based on current literature was employed to estimate outpatient RBC transfusion payments. Total payments per RBC transfusion episode included screening/monitoring (within 3 days, blood acquisition/administration (within 2 days, and associated complications (within 3 days for acute events; up to 45 days for chronic events. Results A total of 3283 patient transfusion episodes were included; 56.4% were men and 40.9% had Medicare supplemental insurance. Mean (standard deviation [SD] age was 60.9 (15.0 years, and mean Charlson comorbidity index was 4.3 (2.5. During a mean (SD follow-up of 495 (474 days, patients had a mean of 2.2 (3.8 outpatient RBC transfusion episodes. Mean/median (SD total payment per RBC transfusion episode was $854/$427 ($2,060 with 72.1% attributable to blood acquisition and administration payments. Complication payments ranged from mean (SD $213 ($168 for delayed hemolytic transfusion reaction to $19,466 ($15,424 for congestive heart failure. Conclusions Payments for outpatient RBC transfusion episodes were driven by blood acquisition and administration payments. While infrequent, transfusion complications increased payments substantially when they occurred.

  17. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn

    2013-01-01

    BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS: The Transfusion...... and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed...

  18. 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.

  19. Impact of red blood cell transfusion on global and regional measures of oxygenation.

    Science.gov (United States)

    Roberson, Russell S; Bennett-Guerrero, Elliott

    2012-01-01

    Anemia is common in critically ill patients. Although the goal of transfusion of red blood cells is to increase oxygen-carrying capacity, there are contradictory results about whether red blood cell transfusion to treat moderate anemia (e.g., hemoglobin 7-10 g/dL) improves tissue oxygenation or changes outcomes. Whereas increasing levels of anemia eventually lead to a level of critical oxygen delivery, increased cardiac output and oxygen extraction are homeostatic mechanisms the body uses to prevent a state of dysoxia in the setting of diminished oxygen delivery due to anemia. In order for cardiac output to increase in the face of anemia, normovolemia must be maintained. Transfusion of red blood cells increases blood viscosity, which may actually decrease cardiac output (barring a state of hypovolemia prior to transfusion). Studies have generally shown that transfusion of red blood cells fails to increase oxygen uptake unless oxygen uptake/oxygen delivery dependency exists (e.g., severe anemia or strenuous exercise). Recently, near-infrared spectroscopy, which approximates the hemoglobin saturation of venous blood, has been used to investigate whether transfusion of red blood cells increases tissue oxygenation in regional tissue beds (e.g., brain, peripheral skeletal muscle). These studies have generally shown increases in near-infrared spectroscopy derived measurements of tissue oxygenation following transfusion. Studies evaluating the effect of transfusion on the microcirculation have shown that transfusion increases the functional capillary density. This article will review fundamental aspects of oxygen delivery and extraction, and the effects of red blood cell transfusion on tissue oxygenation as well as the microcirculation.

  20. Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease.

    Science.gov (United States)

    Desai, Payal C; Deal, Allison M; Pfaff, Emily R; Qaqish, Bahjat; Hebden, Leyna M; Park, Yara A; Ataga, Kenneth I

    2015-08-01

    Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14-27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71-7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66-35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding.

  1. Chronic transfusion practice for children with sickle cell anaemia and stroke.

    Science.gov (United States)

    Aygun, Banu; McMurray, Marsha A; Schultz, William H; Kwiatkowski, Janet L; Hilliard, Lee; Alvarez, Ofelia; Heeney, Matthew; Kalinyak, Karen; Lee, Margaret T; Miller, Scott; Helms, Ronald W; Ware, Russell E

    2009-05-01

    Chronic transfusions to maintain haemoglobin S (HbS) < or =30% are the mainstay of treatment for children with sickle cell anaemia (SCA) and previous stroke. This HbS target is often hard to maintain, however, and values achieved in current practice are unknown. In preparation for the Phase III Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial, we collected data on 295 children with SCA and stroke who received transfusions at 23 institutions. The overall average pre-transfusion %HbS was 35 +/- 11% (institutional range 22-51%). Receiving scheduled transfusions on time was the most predictive variable for maintaining HbS at the < or =30% goal.

  2. Red cell concentrates of hemochromatosis patients comply with the storage guidelines for transfusion purposes.

    NARCIS (Netherlands)

    Luten, M.; Roerdinkholder-Stoelwinder, B.; Rombout-Sestrienkova, E.; Grip, W.J. de; Bos, H.J.; Bosman, G.J.C.G.M.

    2008-01-01

    BACKGROUND: Therapeutic phlebotomy is the preferred treatment for iron overload associated with hemochromatosis. In the Netherlands, red blood cell concentrates (RCCs) from hemochromatosis patients are not used for transfusion purposes. In this study, their storage performance was compared with that

  3. RED-BLOOD-CELL TRANSFUSIONS FOR TOTAL HIP-REPLACEMENT IN A REGIONAL-HOSPITAL - A 6-YEAR ANALYSIS

    NARCIS (Netherlands)

    Biesma, Douwe H.; van Iperen, Charlotte E.; Kraaijenhagen, Rob J.; Marx, Joannes J. M.; van de Wiel, Harry B. M.; van De Wiel, Albert

    1994-01-01

    To evaluate changes in the need for homologous blood and to assess the imp act of autologous blood transfusion, red cell transfusions in unilateral total hip replacement surgery, performed electively in the period 1986-1991, were studied in a regional hospital. Transfusion data, perioperative blood

  4. Duration of red blood cell storage and survival of transfused patients (CME)

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Kamper-Jørgensen, Mads; Eloranta, Sandra;

    2010-01-01

    Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time.......Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time....

  5. In-vitro stem cell derived red blood cells for transfusion: are we there yet?

    Science.gov (United States)

    Kim, Hyun Ok

    2014-03-01

    To date, the use of red blood cells (RBCs) produced from stem cells in vitro has not proved practical for routine transfusion. However, the perpetual and widespread shortage of blood products, problems related to transfusion-transmitted infections, and new emerging pathogens elicit an increasing demand for artificial blood. Worldwide efforts to achieve the goal of RBC production through stem cell research have received vast attention; however, problems with large-scale production and cost effectiveness have yet to prove practical usefulness. Some progress has been made, though, as cord blood stem cells and embryonic stem cells have shown an ability to differentiate and proliferate, and induced pluripotent stem cells have been shown to be an unlimited source for RBC production. However, transfusion of stem cell-derived RBCs still presents a number of challenges to overcome. This paper will summarize an up to date account of research and advances in stem cell-derived RBCs, delineate our laboratory protocol in producing RBCs from cord blood, and introduce the technological developments and limitations to current RBC production practices.

  6. Ex-vivo expansion of red blood cells: How real for transfusion in humans?

    OpenAIRE

    Migliaccio, Anna Rita; Masselli, Elena; Varricchio, Lilian; Whitsett, Carolyn

    2011-01-01

    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. Compa...

  7. Respiratory Impairment after Early Red Cell Transfusion in Pediatric Patients with ALI/ARDS

    Directory of Open Access Journals (Sweden)

    Surender Rajasekaran

    2012-01-01

    Full Text Available Introduction. In the first 48 hours of ventilating patients with acute lung injury (ALI/acute respiratory distress syndrome (ARDS, a multipronged approach including packed red blood cell (PRBC transfusion is undertaken to maintain oxygen delivery. Hypothesis. We hypothesized children with ALI/ARDS transfused within 48 hours of initiating mechanical ventilation would have worse outcome. The course of 34 transfused patients was retrospectively compared to 45 nontransfused control patients admitted to the PICU at Helen DeVos Children’s Hospital between January 1st 2008 and December 31st 2009. Results. Mean hemoglobin (Hb prior to transfusion was 8.2 g/dl compared to 10.1 g/dl in control. P/F ratio decreased from 135.4±7.5 to 116.5±8.8 in transfused but increased from 148.0±8.0 to 190.4±17.8 (P<0.001 in control. OI increased in the transfused from 11.7±0.9 to 18.7±1.6 but not in control. Ventilator days in the transfused were 15.6±1.7 versus 9.5±0.6 days in control (P<0.001. There was a trend towards higher rates of MODS in transfused patients; 29.4% versus 17.7%, odds ratio 1.92, 95% CI; 0.6–5.6 Fisher exact P<0.282. Conclusion. This study suggests that early transfusions of patients with ALI/ARDS were associated with increased ventilatory needs.

  8. Red blood cells transfusions in oncological patients treated with radio- and chemoterapy

    Directory of Open Access Journals (Sweden)

    Antić Ana

    2011-01-01

    Full Text Available Background/Aim. Anemia is one of the most frequent hematology disorders in patients with malignant diseases. It has a great influence on reduction of the quality of life, so it requires early diagnosis and an adequate treatment. The aim of this study was to present and analyze the treatment of anemia using red blood cell transfusions in patients with malignancies, to analyze adequate use of red blood cell transfusions according to hemoglobin concentration, and also the influence of the treatment of malignant disease on the level of anemia and use of red blood cells transfusion. Methods. This retrospective analysis included the data on the use of red blood cells in Oncological Clinic of Clinical Center Niš in a period from the 1st January 2008 to the 31st December 2008. Results. None of the patients received the whole blood. In this period, 735 patients received 1,006 units of red blood cells (red blood cell concentrate, resuspended, washed, filtered. An average use of red blood cell transfusion was 1.37 unit per oncological patient who received transfusion. The use of red blood cell units was adequate (87.60% of patients received transfusion of red cells when Hgb < 80 g/L. During radio- and chemotherapy we noticed a decrease of hematological parameter values. The patients of the experimental group were dependant on red blood cells transfusion. Statistically, a significant decrease of hemoglobin level was observed in patients treated only with radiotherapy who are the greatest consumers of red blood cells. Two patients were registered who more likely to have febrile nonhemolytic transfusion reactions. Posttransfusion alloimmunization occurred in 0.68% of the patients. Conclusion. The use of red blood cells in oncological patients is in compliance with the up to date tendencies and recommendations published in clinical guidelines. For the purpose of efficient transfusion support in patients with malignant diseases, we have to follow the newest

  9. Current issues relating to the transfusion of stored red blood cells.

    Science.gov (United States)

    Zimrin, A B; Hess, J R

    2009-02-01

    The development of blood storage systems allowed donation and transfusion to be separated in time and space. This separation has permitted the regionalization of donor services with subsequent economies of scale and improvements in the quality and availability of blood products. However, the availability of storage raises the question of how long blood products can and should be stored and how long they are safe and effective. The efficacy of red blood cells was originally measured as the increment in haematocrit and safety began with typing and the effort to reduce the risk of bacterial contamination. Appreciation of a growing list of storage lesions of red blood cells has developed with our increasing understanding of red blood cell physiology and our experience with red blood cell transfusion. However, other than frank haemolysis, rare episodes of bacterial contamination and overgrowth, the reduction of oxygen-carrying capacity associated with the failure of some transfused cells to circulate, and the toxicity of lysophospholipids released from membrane breakdown, storage-induced lesions have not had obvious correlations with safety or efficacy. The safety of red blood cell storage has also been approached in retrospective epidemiologic studies of transfused patients, but the results are frequently biased by the fact that sicker patients are transfused more often and blood banks do not issue blood products in a random order. Several large prospective studies of the safety of stored red blood cells are planned.

  10. Intraoperative transfusion practices in Europe

    DEFF Research Database (Denmark)

    Meier, J; Filipescu, D; Kozek-Langenecker, S;

    2016-01-01

    BACKGROUND: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (p...

  11. MR marrow signs of iron overload in transfusion-dependent patients with sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Sheth, S.S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Hurlet, A. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Comerci, S.C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Ruzal-Shapiro, C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Piomelli, S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Berdon, W.E. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States)

    1995-11-01

    Magnetic resonance (MR) marrow signal in the axial and appendicular skeleton of 13 transfusion-dependent and chelated pediatric patients with sickle cell anemia (SSD) was compared with marrow signal in six non-transfusion-dependent patients with SSD. Hepatic, pancreatic, and renal MR signal were also evaluated. Indication for hypertransfusion therapy was primarily prior history of stroke. Transfusion-dependent patients had evidence of iron deposition throughout the imaged marrow and the liver, despite deferoxamine chelation therapy. Non-transfusion-dependent patients did not demonstrate grossly apparent signs of iron overload. Red marrow restoration was present in the spine, pelvis, and long bones and, in some patients, within the epiphyses. Marrow edema secondary to vaso-occlusive crises was evident in the metaphyses and diaphyses of long bones in areas of both red and fatty marrow and was best seen using fat-saturated T2-weighted imaging techniques. (orig.). With 4 figs., 2 tabs.

  12. Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease.

    Science.gov (United States)

    Fasano, Ross M; Booth, Garrett S; Miles, Megan; Du, Liping; Koyama, Tatsuki; Meier, Emily Riehm; Luban, Naomi L C

    2015-01-01

    Sickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro-inflammatory SCD-related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro-inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion-associated pro-inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty-two patients received 3166 pre-storage leuco-reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso-occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate-phosphate-dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro-inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  14. 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.

  15. Respiratory Impairment after Early Red Cell Transfusion in Pediatric Patients with ALI/ARDS.

    Science.gov (United States)

    Rajasekaran, Surender; Sanfilippo, Dominic; Shoemaker, Allen; Curtis, Scott; Zuiderveen, Sandra; Ndika, Akunne; Stoiko, Michael; Hassan, Nabil

    2012-01-01

    Introduction. In the first 48 hours of ventilating patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a multipronged approach including packed red blood cell (PRBC) transfusion is undertaken to maintain oxygen delivery. Hypothesis. We hypothesized children with ALI/ARDS transfused within 48 hours of initiating mechanical ventilation would have worse outcome. The course of 34 transfused patients was retrospectively compared to 45 nontransfused control patients admitted to the PICU at Helen DeVos Children's Hospital between January 1st 2008 and December 31st 2009. Results. Mean hemoglobin (Hb) prior to transfusion was 8.2 g/dl compared to 10.1 g/dl in control. P/F ratio decreased from 135.4 ± 7.5 to 116.5 ± 8.8 in transfused but increased from 148.0 ± 8.0 to 190.4 ± 17.8 (P Fisher exact P < 0.282. Conclusion. This study suggests that early transfusions of patients with ALI/ARDS were associated with increased ventilatory needs.

  16. Clinical observation of factors in the efficacy of blood component transfusion in patients following hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    Full Text Available BACKGROUND: Factors affecting the efficacy of platelet and red blood cell (RBC transfusion in patients undergoing hematopoietic stem cell transplantation (HSCT have not been studied extensively. We aimed to evaluate platelet and RBC transfusion efficacy by measuring the platelet corrected count increment and the hemoglobin increment, respectively, 24 h after transfusion in 105 patients who received HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Using retrospective analysis, we studied whether factors, including gender, time of transplantation, the compatibility of ABO group between HSC donors and recipients, and autologous or allogenic transplantation, influence the efficacy of blood component transfusion. We found that the infection rate of HSCT patients positively correlated with the transfusion amount, and the length of stay in the laminar flow room was associated with transfusion. We found that platelet transfusion performed during HSCT showed significantly better efficacy than that performed before HSCT. The effect of platelet transfusion in auto-transplantation was significantly better than that in allo-transplantation. The efficacy of RBC transfusion during HSCT was significantly lower than that performed before HSCT. The efficacy of RBC transfusion in auto-transplantation was significantly higher than that in allo-transplantation. Allo-transplantation patients who received HSCs from compatible ABO groups showed significantly higher efficacy during both platelet and RBC transfusion. CONCLUSIONS: We conclude that the efficacy of platelet and RBC transfusions does not correlate with the gender of patients, while it significantly correlates with the time of transplantation, type of transplantation, and ABO compatibility between HSC donors and recipients. During HSCT, the infection rate of patients positively correlates with the transfusion amount of RBCs and platelets. The total volume of RBC units transfused positively correlates with the length of

  17. 1601例外科输血患者红细胞输注量与死亡率相关性分析%Correlation analysis of 1601 surgical transfusion and mortality in patients with red blood cell transfusions

    Institute of Scientific and Technical Information of China (English)

    李荣芳; 陈家茂; 杨江存

    2015-01-01

    Objective To explore the relationship between red blood cell transfusion volume and patients' mortality in mas-sive blood transfusion. Methods Multicenter retrospective research was carried out on 1601 surgical inpatients who receiving massive blood transfusion in 20 large comprehensive hospitals in China. According to red blood cell transfusion volume within 24 hours or 72 hours, they are divided into 8 groups: 0-4U, 5-9U, 10-14U, 15-19U, 20-24U, 25-29U, 30-39U, 40U-. The status of patients' death with different red blood cell transfusion volume was analyzed. Results Patients' mortality increases with the in-crease of red blood cell transfusion when total red blood cell transfusion volume ≥10U within 24 or 72 hours. Survival analysis based on different red blood cell transfusion volume was of statistical significance (χ2=72.857, P<0.001). Logistic regression analy-sis reveals that red blood cell transfusion volume was an independent risk factor (OR=0.52;CI:0.43-0.64; P<0.01) for death of pa-tients in massive blood transfusion. When red blood cells were transfused at 5U-9U volume within 24 and 72 hours, mortality is the lowest, which was 3.7% and 2.3% respectively. Conclusions During massive blood transfusion for surgical inpatients, there is some correlation between red blood cell transfusion volume within 24 or 72 hours and mortality of patients. Patients' mortality in-creases with the increase of red blood cell transfusion. Red blood cell transfusion volume, length of stay at hospital and intensive care unit constitute the independent risk factors for patients' death.%目的:联合国内20家大型综合医院多中心回顾性调研外科住院患者大量输血病历1601例,分析探讨红细胞输注量与患者死亡率的关联性。方法联合全国20家三级综合医院进行多中心回顾性分析大量输血病例资料,根据24h内或72h内红细胞输注量分为:0~4U、5~9U、10~14U、15~19U、20~24U、25~29U、30~39U、40~U,8个组

  18. The Nlrp3 Inflammasome Does Not Regulate Alloimmunization to Transfused Red Blood Cells in Mice

    Directory of Open Access Journals (Sweden)

    David R. Gibb

    2016-07-01

    Full Text Available Red blood cell (RBC transfusions are essential for patients with hematological disorders and bone marrow failure syndromes. Despite ABO matching, RBC transfusions can lead to production of alloantibodies against “minor” blood group antigens. Non-ABO alloimmunization is a leading cause of transfusion-associated mortality in the U.S. Despite its clinical importance, little is known about the immunological factors that promote alloimmunization. Prior studies indicate that inflammatory conditions place patients at higher risk for alloimmunization. Additionally, co-exposure to pro-inflammatory pathogen associated molecular patterns (PAMPs promotes alloimmunization in animal models, suggesting that RBC alloimmunization depends on innate immune cell activation. However, the specific innate immune stimuli and sensors that induce a T cell-dependent alloantibody response to transfused RBCs have not been identified. The NLRP3 inflammasome senses chemically diverse PAMPs and damage associated molecular patterns (DAMPs, including extracellular ATP and iron-containing heme. We hypothesized that activation of the NLRP3 inflammasome by endogenous DAMPs from RBCs promotes the alloimmune response to a sterile RBC transfusion. Using genetically modified mice lacking either NLRP3 or multiple downstream inflammasome response elements, we ruled out a role for the NLRP3 inflammasome or any Caspase-1 or -11 dependent inflammasome in regulating RBC alloantibody production to a model antigen.

  19. Red Blood Cell Antigen Genotyping for Sickle Cell Disease, Thalassemia, and Other Transfusion Complications.

    Science.gov (United States)

    Fasano, Ross M; Chou, Stella T

    2016-10-01

    Since the discovery of the ABO blood group in the early 20th century, more than 300 blood group antigens have been categorized among 35 blood group systems. The molecular basis for most blood group antigens has been determined and demonstrates tremendous genetic diversity, particularly in the ABO and Rh systems. Several blood group genotyping assays have been developed, and 1 platform has been approved by the Food and Drug Administration as a "test of record," such that no phenotype confirmation with antisera is required. DNA-based red blood cell (RBC) phenotyping can overcome certain limitations of hemagglutination assays and is beneficial in many transfusion settings. Genotyping can be used to determine RBC antigen phenotypes in patients recently transfused or with interfering allo- or autoantibodies, to resolve discrepant serologic typing, and/or when typing antisera are not readily available. Molecular RBC antigen typing can facilitate complex antibody evaluations and guide RBC selection for patients with sickle cell disease (SCD), thalassemia, and autoimmune hemolytic anemia. High-resolution RH genotyping can identify variant RHD and RHCE in patients with SCD, which have been associated with alloimmunization. In the future, broader access to cost-efficient, high-resolution RBC genotyping technology for both patient and donor populations may be transformative for the field of transfusion medicine.

  20. Effectiveness of a nursing intervention during transfusion of packed red cells on the patient´s anxiety state receiver

    Directory of Open Access Journals (Sweden)

    Jesús Fernando Martín Díaz

    2012-05-01

    Full Text Available The transfusion provokes anxiety and this one compromises the improvement of the patient. Objetive: The study aims to evaluate whether a nursing intervention protocol-through oral and written submissions previous to the transfusion of packed red blood cells decreases anxiety levels in pretransfusion and postransfusion recipient patients through a randomized clinical trial. Methodology: Be conducted in patients over 18 years admitted in the Hospitable complex of Toledo, prescription transfusion of packed red blood cells. For an alpha error 0.05, beta error of 0.90, with an expected effect of 10%, need 70 subjects in each group. The allocation to the intervention group and the control group was randomly made simple. The performance in the normal control group will be done in the hospital, patients receiving transfusion. As dependent variables evaluated:- The anxiety level pretransfusion and postransfusion. Using the questionnaire was validated by Spielberger (STAI. - The level of satisfaction perceived by the user on the information received prior to transfusion. By design developed for this study. Also recorded other control variables: sex, age, socio-cultural level, marital status, reason for transfusion, or no knowledge of the prescription of transfusion, incidents during transfusion.Scientific and sociosanitary relevancy of the study: The results will allow to know if the transfusion increases the anxiety and if an educational intervention nurse can diminish it; and to do the intervention before every transfusion.

  1. Delayed hemolytic transfusion reaction presenting as a painful crisis in a patient with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Antonio Fabron Junior

    1999-01-01

    Full Text Available CONTEXT: Patients with sickle cell anemia (SCA are frequently transfused with red blood cells (RBC. Recently, we reported that the calculated risk of RBC alloimmunization per transfused unit in Brazilian patients with SCA is 1.15%. We describe a delayed hemolytic transfusion reaction (DHTR presenting as a painful crisis in a patient with SCA. CASE REPORT: A 35-year-old Brazilian female with homozygous SCA was admitted for a program of partial exchange transfusion prior to cholecystectomy. Her blood group was O RhD positive and no atypical RBC alloantibody was detected using the indirect antiglobulin technique. Pre-transfusional hemoglobin (Hb was 8.7 g/dL and isovolumic partial exchange transfusion was performed using 4 units of ABO compatible packed RBC. Five days after the last transfusion she developed generalized joint pain and fever of 39°C. Her Hb level dropped from 12.0 g/dL to 9.3 g/dL and the unconjugated bilirrubin level rose to 27 mmol/L. She was jaundiced and had hemoglobinuria. Hemoglobin electrophoresis showed 48.7% HbS, 46.6% HbA1, 2.7% HbA2, and 2.0% HbF. The patient’s extended RBC phenotype was CDe, K-k+, Kp(a-b+, Fy(a-b-, M+N+s+, Le(a+b-, Di(a-. An RBC alloantibody with specificity to the Rh system (anti-c, titer 1:16.384 was identified by the indirect antiglobulin test. The Rh phenotype of the RBC used in the last packed RBC transfusion was CcDEe. The patient was discharged, asymptomatic, 7 days after admission.

  2. Phenotypic differences of CD4(+) T cells in response to red blood cell immunization in transfused sickle cell disease patients.

    Science.gov (United States)

    Vingert, Benoît; Tamagne, Marie; Habibi, Anoosha; Pakdaman, Sadaf; Ripa, Julie; Elayeb, Rahma; Galacteros, Frédéric; Bierling, Philippe; Ansart-Pirenne, Hélène; Bartolucci, Pablo; Noizat-Pirenne, France

    2015-06-01

    Alloimmunization against red blood cells (RBCs) is the main immunological risk associated with transfusion in patients with sickle cell disease (SCD). However, about 50-70% of SCD patients never get immunized despite frequent transfusion. In murine models, CD4(+) T cells play a key role in RBC alloimmunization. We therefore explored and compared the CD4(+) T-cell phenotypes and functions between a group of SCD patients (n = 11) who never became immunized despite a high transfusion regimen and a group of SCD patients (n = 10) who had become immunized (at least against Kidd antigen b) after a low transfusion regimen. We studied markers of CD4(+) T-cell function, including TLR, that directly control lymphocyte function, and their spontaneous cytokine production. We also tested responders for the cytokine profile in response to Kidd antigen b peptides. Low TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4(+) T cells were associated with the nonresponder status, whereas spontaneous expression of IL-10 by CD4(+) T cells and weak Tbet expression were associated with the responder status. A Th17 profile was predominant in responders when stimulated by Jb(k) . These findings implicate CD4(+) T cells in alloimmunization in humans and suggest that they may be exploited to differentiate responders from nonresponders.

  3. Reducing red cell transfusion by audit, education and a new guideline in a large teaching hospital.

    Science.gov (United States)

    Garrioch, M; Sandbach, J; Pirie, E; Morrison, A; Todd, A; Green, R

    2004-02-01

    Safety concerns combined with the greatly increased costs and difficulties of maintaining the blood supply are major considerations for transfusion services. Previous local surveys demonstrated that hospital blood use at our hospital could be improved. Excessive cross-matching, unnecessary transfusion and high return rates of unused blood were commonplace. Transfusion practice was audited over a 3-month period. An education package with guidelines for transfusion was delivered to all clinician groups within the hospital, over the following 9 months. The audit was repeated exactly 1 year later at the same time period. During the second audit, inpatient hospital numbers increased by 1.02% (from n = 7262 to n = 7336) but no differences in length of stay, cardiovascular morbidity or mortality were demonstrated. Twenty percent (n = 254, 2002; n = 316, 2001) fewer patients received blood, and the number of red cell packs used reduced by 19% (from n = 1093 to n = 880). Total number of patients transfused reduced from 4.4% to 3.5% which, as an absolute difference, is a reduction of 0.9% (CI 0.3-1.5, P = 0.006). The audit, guideline and education package had a major impact on red cell use within the hospital with no adverse effects. Blood use can be improved by the implementation of a suitable education package and guideline. If it is possible to replicate the results of this education programme nationwide, the effect on blood use, with subsequent savings and enhanced patient safety could be significant.

  4. Features of transfusion therapy in patients undergoing hematopoietic stem cell transplantation. Review of the literature

    Directory of Open Access Journals (Sweden)

    D. N. Balashov

    2013-01-01

    Full Text Available The indications for transfusion of blood components support after stem cell transplantation (SCT usually do not differ form other clinical situations, but the rules for such therapy have a number of features. One of them is the possibility of inconsistence of AB0 group between donor and recipient of hematopoietic stem cells, which is not only fraught with the development of various alloimmune complications, but also fundamentally changes the standards for the selection of blood components for transfusion. A major problem after HSCT is a secondary immunodeficiency, which is important to consider for ensuring prevention of transfusion-transmitted infections (eg, CMV, as well as to carry out activities aimed for the prevention of transfusion- associated graft-versus-host disease. HSCT is a medical technology today, the effectiveness of which is often dependent on the accuracy and integrity of its implementation. So, serious attitude to various supportive therapy, including transfusions of blood components is an important component which determines the success of the treatment.

  5. Features of transfusion therapy in patients undergoing hematopoietic stem cell transplantation. Review of the literature

    Directory of Open Access Journals (Sweden)

    D. N. Balashov

    2014-07-01

    Full Text Available The indications for transfusion of blood components support after stem cell transplantation (SCT usually do not differ form other clinical situations, but the rules for such therapy have a number of features. One of them is the possibility of inconsistence of AB0 group between donor and recipient of hematopoietic stem cells, which is not only fraught with the development of various alloimmune complications, but also fundamentally changes the standards for the selection of blood components for transfusion. A major problem after HSCT is a secondary immunodeficiency, which is important to consider for ensuring prevention of transfusion-transmitted infections (eg, CMV, as well as to carry out activities aimed for the prevention of transfusion- associated graft-versus-host disease. HSCT is a medical technology today, the effectiveness of which is often dependent on the accuracy and integrity of its implementation. So, serious attitude to various supportive therapy, including transfusions of blood components is an important component which determines the success of the treatment.

  6. Predictors of red blood cell transfusion after cardiac surgery: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Camila Takao Lopes

    2015-12-01

    Full Text Available Abstract OBJECTIVE To identify predictors of red blood cell transfusion (RBCT after cardiac surgery. METHOD A prospective cohort study performed with 323 adults after cardiac surgery, from April to December of 2013. A data collection instrument was constructed by the researchers containing factors associated with excessive bleeding after cardiac surgery, as found in the literature, for investigation in the immediate postoperative period. The relationship between risk factors and the outcome was assessed by univariate analysis and logistic regression. RESULTS The factors associated with RBCT in the immediate postoperative period included lower height and weight, decreased platelet count, lower hemoglobin level, higher prevalence of platelet count <150x10 3/mm3, lower volume of protamine, longer duration of anesthesia, higher prevalence of intraoperative RBCT, lower body temperature, higher heart rate and higher positive end-expiratory pressure. The independent predictor was weight <66.5Kg. CONCLUSION Factors associated with RBCT in the immediate postoperative period of cardiac surgery were found. The independent predictor was weight.

  7. 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....

  8. Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq.

    Science.gov (United States)

    Al-Mousawi, Muqdad M N; Al-Allawi, Nasir A S; Alnaqshabandi, Rubad

    2015-01-01

    Hemoglobinopathies are significant health problems in Iraq, including its Northern Kurdistan region. One of the essential components of management of these disorders is regular lifelong blood transfusions. The latter is associated with several complications including red cell alloimmunization. No study has looked at the frequency of alloimmunization and its associations in the country. To address the latter issue, 401 multi transfused patients [311 with β-thalassemia (β-thal) syndrome and 90 with sickle cell disease], registered at a large thalassemia care center in Iraqi Kurdistan had their records reviewed, and their sera tested for atypical antibodies using screening and extended red cell panels. Red cell alloimmunization was detected in 18 patients (4.5%) with a total of 20 alloantibodies, while no autoantibodies were detected. The most frequent alloantibody was anti-E, followed by anti-D, anti-K, anti-C(w), anti-C, anti-c and anti-Le(a). Ethnicity was an important predictor of alloimmunization, while age at start of transfusion (>2 vs. ≤2 years) (p = 0.005), Rhesus D (RhD) negative status (p = 0.0017) and history of previous transfusion reactions (p = 0.007) showed a statistically significant higher rate of alloimmunization. However, patients' age, gender, number of units transfused, underlying diagnosis and splenectomy were not significantly associated with alloimmunization. Based on our observations, measures to reduce alloimmunization rates may include extended matching for Rhesus and Kell antigens and early initiation of blood transfusions.

  9. Post-transfusion purpura treated with plasma exchange by haemonetics cell separator. A case report

    DEFF Research Database (Denmark)

    Laursen, B; Morling, N; Rosenkvist, J;

    1978-01-01

    A case of post-transfusion purpura in a 61-year-old, multiparous female with a platelet alloantibody (anti-Zwa) in her serum is reported. The patient was successfully treated with plasma exchange by means of a Haemonetics 30 cell separator and corticosteroids. Compared with other therapeutic meas...

  10. 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)

  11. 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...

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

    Science.gov (United States)

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

    2016-05-01

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

  13. Cholecystectomy in sickle cell anemia patients : Perioperative outcome of 364 cases from the national preoperative transfusion study

    NARCIS (Netherlands)

    Haberkern, CM; Neumayr, LD; Orringer, EP; Earles, AN; Robertson, SM; Abboud, MR; Koshy, M; Idowu, O; Vichinsky, EP; Black, D.

    1997-01-01

    Cholecystectomy is the most common surgical procedure performed in sickle cell anemia (SCA) patients. We investigated the effects of transfusion and surgical method on perioperative outcome. A total of 364 patients underwent cholecystectomy: group 1 (randomized to aggressive transfusion) 110 patient

  14. Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion.

    Science.gov (United States)

    Elayeb, Rahma; Tamagne, Marie; Bierling, Philippe; Noizat-Pirenne, France; Vingert, Benoît

    2016-02-01

    Murine models of red blood cell transfusion show that inflammation associated with viruses or methylated DNA promotes red blood cell alloimmunization. In vaccination studies, the intensity of antigen-specific responses depends on the delay between antigen and adjuvant administration, with a short delay limiting immune responses. In mouse models of alloimmunization, the delay between the injection of Toll-like receptor agonists and transfusion is usually short. In this study, we hypothesized that the timing of Toll-like receptor 3 agonist administration affects red blood cell alloimmunization. Poly(I:C), a Toll-like receptor 3 agonist, was administered to B10BR mice at various time points before the transfusion of HEL-expressing red blood cells. For each time point, we measured the activation of splenic HEL-presenting dendritic cells, HEL-specific CD4(+) T cells and anti-HEL antibodies in serum. The phenotype of activated immune cells depended on the delay between transfusion and Toll-like receptor-dependent inflammation. The production of anti-HEL antibodies was highest when transfusion occurred 7 days after agonist injection. The proportion of HEL-presenting CD8α(+) dendritic cells producing interleukin-12 was highest in mice injected with poly(I:C) 3 days before transfusion. Although the number of early-induced HEL-specific CD4(+) T cells was similar between groups, a high proportion of these cells expressed CD134, CD40 and CD44 in mice injected with poly(I:C) 7 days before transfusion. This study clearly shows that the delay between transfusion and Toll-like receptor-induced inflammation influences the immune response to transfused red blood cells.

  15. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Science.gov (United States)

    Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

    2016-01-01

    Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  16. Revisiting transfusion safety and alternatives to transfusion.

    Science.gov (United States)

    Schoettker, Patrick; Marcucci, Carlos E; Casso, Gabriele; Heim, Catherine

    2016-01-01

    Transfusion of blood products can be life saving when used appropriately. It carries however at the same time a potential for morbidity and mortality, depending on the patient, the product or the setting. Numerous strategies have been elaborated to minimize these risks, and in recent years, transfusion has no longer been regarded as essential for the management of a wide range of diseases. Uncomplicated surgeries in well-prepared patients can now be conducted without the use of transfusions. Questions about transfusion safety and shortage have led to extensive research on alternatives to blood transfusion, ranging from non-pharmacological to pharmacological solutions. Restrictive transfusion therapies, preoperative autologous blood donations, perioperative red cell salvage, acute normovolaemic haemodilution techniques or patient blood management are potential solutions where prothrombin complex or fibrinogen concentrates, synthetic anti-fibrinolytic agents, desmopressin, rFVIIa, or erythropoiesis stimulating agents may play a complementary pharmacologic role.

  17. Severe neurologic complication after delayed hemolytic transfusion reaction in 2 children with sickle cell anemia: significant diagnosis and therapeutic challenges.

    Science.gov (United States)

    Elenga, Narcisse; Mialou, Valérie; Kebaïli, Kamila; Galambrun, Claire; Bertrand, Yves; Pondarre, Corinne

    2008-12-01

    Although delayed hemolytic transfusion reaction (DHTR) has been widely recognized as a serious complication of red blood cell transfusion in patients with sickle cell disease (SCD), there is no consensus on its optimal management. Discontinuation of transfusion is recommended, whereas corticosteroids and immunoglobulins are considered to be beneficial. We report 2 children with sickle cell anemia who were diagnosed with DHTR and experienced a subsequent neurologic event in the course of treatment with corticosteroids. The role of corticosteroids as possible precipitating factors of neurologic complications is discussed. Pending a better understanding of the chain of events of DHTR, SCD children with DHTR should receive steroids with great caution.

  18. Transfusão de concentrado de hemácias na unidade de terapia intensiva Red blood cells transfusion in intensive care unit

    Directory of Open Access Journals (Sweden)

    Solange Emanuelle Volpato

    2009-12-01

    Full Text Available INTRODUÇÃO: A anemia é um problema comum na admissão dos pacientes nas unidades de terapia intensiva, sendo a prática de transfusão de concentrado de hemácias uma terapêutica freqüente. As causas de anemia em pacientes críticos que realizam transfusão de concentrado de hemácias são várias: perda aguda de sangue após trauma, hemorragia gastrointestinal, cirurgia, dentre outras. Atualmente, poucos estudos são disponibilizados sobre o uso de hemocomponentes em pacientes sob cuidados intensivos. Embora as transfusões sangüíneas sejam freqüentes em unidades de terapia intensiva, os critérios de manejo otimizados não são claramente definidos, não existindo, inclusive, guidelines específicos. OBJETIVOS: Analisar as indicações clínicas do uso do concentrado hemácia na unidade de terapia intensiva. MÉTODOS: Foram analisados os prontuários dos pacientes internados na unidade de terapia intensiva que realizaram transfusão de concentrado de hemácias no período de 1º de janeiro de 2005 a 31 de dezembro de 2005. O trabalho foi aceito pelo Comitê de Ética em Pesquisa da Universidade do Sul de Santa Catarina (UNISUL. RESULTADOS: A taxa de transfusão foi de 19,33%, tendo predomínio do gênero masculino. Prevalência de paciente com idade superior ou igual a 60 anos. A taxa de óbitos nos pacientes transfundidos com concentrado de hemácias foi de 38,22%. O critério de indicação de transfusão mais freqüente foi por baixa concentração de hemoglobina (78% com média da hemoglobina pré-transfusional de 8,11g/dl. CONCLUSÕES: Os diagnósticos pré-transfusão mais frequentes são politrauma e sepse/choque séptico. Baixa concentração de hemoglobina é o principal critério clínico com média pré-transfusional de 8,11g/dl.BACKGROUND: The anemia is a common problem upon admission of the patients in the intensive care unit being the red blood cell transfusion a frequent therapeutic. The causes of anemia in critical

  19. Fatal hyperkalemia due to rapid red cell transfusion in a critically ill patient.

    Science.gov (United States)

    Tsukamoto, Sakiko; Maruyama, Koichi; Nakagawa, Hideyuki; Iwase, Yoshinori; Kitamura, Akira; Hayashida, Masakazu

    2009-10-01

    A 60-year-old woman in severe hemorrhagic shock underwent urgent laparotomy to control massive hematemesis. Severe metabolic acidosis due to hemorrhagic shock and hyperkalemia as well as hypocalcemia associated with rapid blood transfusion were aggressively corrected with administration of sodium bicarbonate, insulin, and calcium chloride. Following rapid transfusion of the last 8 units of red cell concentrate (RCC), however, cardiac arrest occurred because of hyperkalemia and did not respond to cardiopulmonary resuscitation. Blood gas analysis revealed that the serum K(+) concentration had increased from 4.05 to 8.24 mEq/L over a 7-minute period, while the Ca(2+) concentration had decreased from 1.43 to 0.53 mmol/L. Rapid transfusion of irradiated RCC containing a high concentration of K(+), an extreme decrease in the circulating blood volume to dilute the exogenously administered K(+) and citrate, and severe metabolic acidosis impeding the intracellular shift of K(+) seemed to have contributed to the extremely rapid development of fetal hyperkalemia accompanied by hypocalcemia. Anesthesiologists must be aware that hyperkalemia due to rapid blood transfusion can develop extremely rapidly in patients in severe hemorrhagic shock.

  20. Evaluation of Hematological Parameters in Partial Exchange and Packed Cell Transfusion in Treatment of Severe Anemia in Pregnancy

    Directory of Open Access Journals (Sweden)

    Sudha Salhan

    2012-01-01

    Full Text Available Objectives. Anemia is a major public health problem throughout the world which assumes prominence in pregnant mothers. Patients with severe anemia continue to present themselves at term or in labor. This study was conducted to compare the improvements in hematological parameters of patients receiving partial exchange blood transfusion and transfusion of packed cells without exchange. Methods. One hundred and twenty-five severely anemic antenatal mothers were admitted from outpatient service. Partial exchange transfusion was given to sixty-six patients while fifty-nine received transfusion of packed cells with frusemide cover. Results. The two groups were comparable in terms of age, height, weight, religion, diet, education, occupation of self and husband, and income. Hemoglobin level in Group 1 was comparatively less than Group 2 at prelevel (5.2±1.5 versus 6.6±2.3, P=0.001 and postlevel (7.2±1.5 versus 8.6±1.8, P=0.001, respectively, but there was no significant difference between the two modes of transfusion (2.09±1.6 versus 2.01±1.5, P=0.78. Conclusion. The study produced an equally significant improvement in hematological parameters in partial exchange and packed cell transfusion. Platelet counts were significantly less in partial exchange as compared with packed cell transfusion.

  1. Evaluation of hematological parameters in partial exchange and packed cell transfusion in treatment of severe anemia in pregnancy.

    Science.gov (United States)

    Salhan, Sudha; Tripathi, Vrijesh; Singh, Rajvir; Gaikwad, Harsha S

    2012-01-01

    Objectives. Anemia is a major public health problem throughout the world which assumes prominence in pregnant mothers. Patients with severe anemia continue to present themselves at term or in labor. This study was conducted to compare the improvements in hematological parameters of patients receiving partial exchange blood transfusion and transfusion of packed cells without exchange. Methods. One hundred and twenty-five severely anemic antenatal mothers were admitted from outpatient service. Partial exchange transfusion was given to sixty-six patients while fifty-nine received transfusion of packed cells with frusemide cover. Results. The two groups were comparable in terms of age, height, weight, religion, diet, education, occupation of self and husband, and income. Hemoglobin level in Group 1 was comparatively less than Group 2 at prelevel (5.2 ± 1.5 versus 6.6 ± 2.3, P = 0.001) and postlevel (7.2 ± 1.5 versus 8.6 ± 1.8, P = 0.001), respectively, but there was no significant difference between the two modes of transfusion (2.09 ± 1.6 versus 2.01 ± 1.5, P = 0.78). Conclusion. The study produced an equally significant improvement in hematological parameters in partial exchange and packed cell transfusion. Platelet counts were significantly less in partial exchange as compared with packed cell transfusion.

  2. Health-related quality of life in children with sickle cell anemia: impact of blood transfusion therapy.

    Science.gov (United States)

    Beverung, Lauren M; Strouse, John J; Hulbert, Monica L; Neville, Kathleen; Liem, Robert I; Inusa, Baba; Fuh, Beng; King, Allison; Meier, Emily Riehm; Casella, James; DeBaun, Michael R; Panepinto, Julie A

    2015-02-01

    The completion of the Multicenter Silent Infarct Transfusion Trial demonstrated that children with pre-existing silent cerebral infarct and sickle cell anemia (SCA) who received regular blood transfusion therapy had a 58% relative risk reduction of infarct recurrence when compared to observation. However, the total benefit of blood transfusion therapy, as assessed by the parents, was not measured against the burden of monthly blood transfusion therapy. In this planned ancillary study, we tested the hypothesis that a patient centered outcome, health-related quality of life (HRQL), would be greater in participants randomly assigned to the blood transfusion therapy group than the observation group. A total of 89% (175 of 196) of the randomly allocated participants had evaluable entry and exit HRQL evaluations. The increase in Change in Health, measured as the child's health being better, was significantly greater for the transfusion group than the observation group (difference estimate = -0.54, P ≤ 0.001). This study provides the first evidence that children with SCA who received regular blood transfusion therapy felt better and had better overall HRQL than those who did not receive transfusion therapy.

  3. Transfusion medicine

    Energy Technology Data Exchange (ETDEWEB)

    Murawski, K.; Peetoom, F.

    1986-01-01

    These proceedings contain 24 selections, including papers presented at the conference of American Red Cross held in May 1985, on the Subject of transfusion medicine. Some of the titles are: Fluosol/sup R/-DA in Radiation Therapy; Expression of Cloned Human Factor VIII and the Molecular Basis of Gene Defects that Cause Hemophilia; DNA-Probing Assay in the Detection of Hepatitis B Virus Genome in Human Peripheral Blood Cells; and Monoclonal Antibodies: Convergence of Technology and Application.

  4. Admission red cell distribution width: a novel predictor of massive transfusion after injury.

    Science.gov (United States)

    Paulus, Elena M; Weinberg, Jordan A; Magnotti, Louis J; Sharpe, John P; Schroeppel, Thomas J; Fabian, Timothy C; Croce, Martin A

    2014-07-01

    Admission red cell distribution width (aRDW) has been shown to predict mortality in trauma patients by an unclear mechanism. It has been speculated that aRDW is a marker of chronic health status, but elevated RDW may also reflect recent hemorrhage. We hypothesized that aRDW is a predictor of major hemorrhage in trauma patients. Shock trauma patients at a Level I trauma center over 6.5 years were evaluated. Patients were stratified by aRDW quintile (Q1: less than 13%, Q2: 13.1 to 13.5%, Q3: 13.6 to 14.0%, Q4: 14.1 to 14.9%, Q5: 15.0% or greater). Massive transfusion (MT) was defined as 10 or more packed red blood cells in the first 24 hours. From multiple logistic regression, odds ratios with 95 per cent confidence intervals (CIs) were determined to evaluate the association between aRDW quintile and MT. Three thousand nine hundred ninety-four met study criteria. Overall MT incidence was 10 per cent and in-hospital mortality was 17 per cent. MT and mortality increased in a stepwise fashion by aRDW quintile (P < 0.0001). From logistic regression, a threefold increased odds of MT was associated with aRDW Q4 (CI, 1.81 to 4.92), and a 3.5-fold increased odds of MT was associated with aRDW Q5 (CI, 2.70 to 5.83). aRDW independently predicted MT, suggesting that elevated aRDW is an indicator of major hemorrhage in trauma patients. The association between aRDW and mortality in trauma patients may be explained by acute hemorrhage rather than chronic health status.

  5. Non-invasive spectroscopy of transfusable red blood cells stored inside sealed plastic blood-bags.

    Science.gov (United States)

    Buckley, K; Atkins, C G; Chen, D; Schulze, H G; Devine, D V; Blades, M W; Turner, R F B

    2016-03-07

    After being separated from (donated) whole blood, red blood cells are suspended in specially formulated additive solutions and stored (at 4 °C) in polyvinyl chloride (PVC) blood-bags until they are needed for transfusion. With time, the prepared red cell concentrate (RCC) is known to undergo biochemical changes that lower effectiveness of the transfusion, and thus regulations are in place that limit the storage period to 42 days. At present, RCC is not subjected to analytical testing prior to transfusion. In this study, we use Spatially Offset Raman Spectroscopy (SORS) to probe, non-invasively, the biochemistry of RCC inside sealed blood-bags. The retrieved spectra compare well with conventional Raman spectra (of sampled aliquots) and are dominated by features associated with hemoglobin. In addition to the analytical demonstration that SORS can be used to retrieve RCC spectra from standard clinical blood-bags without breaking the sterility of the system, the data reveal interesting detail about the oxygenation-state of the stored cells themselves, namely that some blood-bags unexpectedly contain measurable amounts of deoxygenated hemoglobin after weeks of storage. The demonstration that chemical information can be obtained non-invasively using spectroscopy will enable new studies of RCC degeneration, and points the way to a Raman-based instrument for quality-control in a blood-bank or hospital setting.

  6. Hyperkalemia after irradiation of packed red blood cells: Possible effects with intravascular fetal transfusion

    Energy Technology Data Exchange (ETDEWEB)

    Thorp, J.A.; Plapp, F.V.; Cohen, G.R.; Yeast, J.D.; O' Kell, R.T.; Stephenson, S. (St. Luke' s Perinatal Center, Kansas City, MO (USA))

    1990-08-01

    Plasma potassium, calcium, and albumin concentrations in irradiated blood, and in fetal blood before and after transfusion, were measured. Dangerously high plasma potassium levels were observed in some units of irradiated packed red blood cells (range, 13.9 to 66.5 mEq/L; mean, 44.7 mEq/L) and could be one possible explanation for the high incidence of fetal arrhythmia associated with fetal intravascular transfusion. There are many factors operative in the preparation of irradiated packed red blood cells that may predispose to high potassium levels: the age of the red blood cells, the number of procedures used to concentrate the blood, the duration of time elapsed from concentration, the duration of time elapsed from irradiation, and the hematocrit. Use of fresh blood, avoidance of multiple packing procedures, limiting the hematocrit in the donor unit to less than or equal to 80%, and minimizing the time between concentration, irradiation and transfusion may minimize the potassium levels, and therefore making an additional washing procedure unnecessary.

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

    Science.gov (United States)

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

    2015-02-01

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

  8. Evaluation of a filter-syringe set for preparation of packed cell aliquots for neonatal transfusion.

    Science.gov (United States)

    Chambers, L A

    1995-09-01

    A closed-system filter-syringe set designed for preparation of prefiltered aliquots of packed red cells for neonatal transfusion was evaluated. In three experiments, filter-syringe sets were sterile-connected, and aliquots were prepared at six intervals during 35-day storage of CPDA-1 packed cells. Hemoglobin (HGB), supernatant potassium (K+), and free hemoglobin (fHGB) in the aliquot and primary storage container were compared. There was no tubing weld failure, filter-occlusion, or bacterial contamination of the units. Hemoglobin remained stable over 35 days of storage, with comparable values in the primary collection container and syringe aliquot. Supernatant potassium in the units increased to an average of 89.5 mEq/L at 35 days, and levels in the aliquots closely matched those in the primary containers at each storage interval (maximum average 91.8 mEq/L). Free hemoglobin also progressively and comparably increased in both the primary containers and syringe aliquots. The gentle negative pressure and turbulence during use of the filter-syringe set apparently causes little hemolysis. The set simplifies preparation of aliquots for neonatal small volume and syringe-pump transfusion at costs comparable to alternative preparation methods. When sterile-connected, the filter-syringe set facilitates "assigned unit" inventory management for neonatal transfusion, which has been shown to be highly effective in limiting donor exposures.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

    Hogman, CF; Meryman, HT

    2006-01-01

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

  11. Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

    Science.gov (United States)

    Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

    2016-02-01

    Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (pvolume from 39.7 to 64.1 ml/m2 (pvolume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children.

  12. Cost-effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial.

    Science.gov (United States)

    Spackman, Eldon; Sculpher, Mark; Howard, Jo; Malfroy, Moira; Llewelyn, Charlotte; Choo, Louise; Hodge, Renate; Johnson, Tony; Rees, David C; Fijnvandraat, Karin; Kirby-Allen, Melanie; Davies, Sally; Williamson, Lorna

    2014-03-01

    The study's objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Sß(0) thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the 'within-trial' analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from -£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY.

  13. [Transfusions in geriatrics].

    Science.gov (United States)

    Moulias, Sophie; Lesure, Christine

    2015-01-01

    Elderly people are Darticularlv Drone to anaemia and the need for transfusions. However, in response to the known adverse effects of red blood cell transfusions, particularly in the context of chronic anaemia, new recommendations have been issued. it is always necessary to consider this procedure on a case-by-case basis, analysing the risk-benefit ratio.

  14. A randomized trial of washed red blood cell and platelet transfusions in adult acute leukemia [ISRCTN76536440

    Directory of Open Access Journals (Sweden)

    Rowe Jacob M

    2004-12-01

    Full Text Available Abstract Background Platelet transfusion is universally employed in acute leukemia. Platelet concentrate supernatants contain high concentrations of biologic mediators that might impair immunity. We investigated whether washed platelet and red cell transfusions could improve clinical outcomes in adult patients with acute leukemia. Methods A pilot randomized trial of washed, leukoreduced ABO identical transfusions versus leukoreduced ABO identical transfusions was conducted in 43 adult patients with acute myeloid or lymphoid leukemia during 1991–94. Primary endpoints to be evaluated were platelet transfusion refractoriness, infectious and bleeding complications and overall survival. Results There were no significant differences in infectious or major bleeding complications and only one patient required HLA matched platelet transfusions. Minor bleeding was more frequent in the washed, leukoreduced arm of the study. Confirmed transfusion reactions were more frequent in the leukoreduced arm of the study. Overall survival was superior in the washed arm of the study (40% versus 22% at 5 years, but this difference was not statistically significant (p = 0.36. A planned subset analysis of those ≤50 years of age found that those in the washed, leukoreduced arm (n = 12 had a 75% survival at five years compared with 30% in the leukoreduced arm (n = 10 (p = 0.037 Conclusion This study provides the first evidence concerning the safety and efficacy of washed platelets, and also raises the possibility of improved survival. We speculate that transfusion of stored red cell and platelet supernatant may compromise treatment, particularly in younger patients with curable disease. Larger trials will be needed to assess this hypothesis.

  15. Red cell transfusion trigger-avoiding the highs and the lows

    Institute of Scientific and Technical Information of China (English)

    Paul M.Ness

    2010-01-01

    @@ One of the most vexing problems in AIHA is handling the acute situation where all blood is incompatible and the patient has severe,worsening anemia.Since the panagglutinin in the patient's serum typically reacts with all donor red cells,crossmatching donor blood is a difficult and time consuming process and probably of little benefit.The most pressing problem in a patient with previous pregnancies or transfusions is detecting alloantibody which may be hidden by the autoantibody.Sophisticated immunohematology laboratories can use a combination of procedures including differential adsorption and warm autoadsorption to identify underlying alloantibodies.

  16. Alloimmune refractoriness to platelet transfusions.

    Science.gov (United States)

    Sandler, S G

    1997-11-01

    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  17. CD8+ T cells mediate antibody-independent platelet clearance in mice.

    Science.gov (United States)

    Arthur, Connie M; Patel, Seema R; Sullivan, H Cliff; Winkler, Annie M; Tormey, Chris A; Hendrickson, Jeanne E; Stowell, Sean R

    2016-04-07

    Platelet transfusion provides an important therapeutic intervention in the treatment and prevention of bleeding. However, some patients rapidly clear transfused platelets, preventing the desired therapeutic outcome. Although platelet clearance can occur through a variety of mechanisms, immune-mediated platelet removal often plays a significant role. Numerous studies demonstrate that anti-platelet alloantibodies can induce significant platelet clearance following transfusion. In fact, for nearly 50 years, anti-platelet alloantibodies were considered to be the sole mediator of immune-mediated platelet clearance in platelet-refractory individuals. Although nonimmune mechanisms of platelet clearance can often explain platelet removal in the absence of anti-platelet alloantibodies, many patients experience platelet clearance following transfusion in the absence of a clear mechanism. These results suggest that other processes of antibody-independent platelet clearance may occur. Our studies demonstrate that CD8(+)T cells possess the unique ability to induce platelet clearance in the complete absence of anti-platelet alloantibodies. These results suggest a previously unrecognized form of immune-mediated platelet clearance with significant implications in the appropriate management of platelet-refractory individuals.

  18. International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Cancun report (2012).

    Science.gov (United States)

    Storry, J R; Castilho, L; Daniels, G; Flegel, W A; Garratty, G; de Haas, M; Hyland, C; Lomas-Francis, C; Moulds, J M; Nogues, N; Olsson, M L; Poole, J; Reid, M E; Rouger, P; van der Schoot, E; Scott, M; Tani, Y; Yu, L-C; Wendel, S; Westhoff, C; Yahalom, V; Zelinski, T

    2014-07-01

    The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

  19. Prediction of escape red blood cell transfusion in expectantly managed women with acute anaemia after postpartum haemorrhage

    NARCIS (Netherlands)

    Prick, B. W.; Schuit, E.; Mignini, L.; Jansen, A. J. G.; van Rhenen, D. J.; Steegers, E. A. P.; Mol, B. W.; Duvekot, J. J.

    2015-01-01

    ObjectiveTo determine clinical predictors of escape red blood cell (RBC) transfusion in postpartum anaemic women, initially managed expectantly, and the additional predictive value of health-related quality of life (HRQoL) measures. DesignSecondary analysis of women after postpartum haemorrhage, eit

  20. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    Science.gov (United States)

    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

  1. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  2. Transfusion practices in trauma

    Directory of Open Access Journals (Sweden)

    V Trichur Ramakrishnan

    2014-01-01

    Full Text Available Resuscitation of a severely traumatised patient with the administration of crystalloids, or colloids along with blood products is a common transfusion practice in trauma patients. The determination of this review article is to update on current transfusion practices in trauma. A search of PubMed, Google Scholar, and bibliographies of published studies were conducted using a combination of key-words. Recent articles addressing the transfusion practises in trauma from 2000 to 2014 were identified and reviewed. Trauma induced consumption and dilution of clotting factors, acidosis and hypothermia in a severely injured patient commonly causes trauma-induced coagulopathy. Early infusion of blood products and early control of bleeding decreases trauma-induced coagulopathy. Hypothermia and dilutional coagulopathy are associated with infusion of large volumes of crystalloids. Hence, the predominant focus is on damage control resuscitation, which is a combination of permissive hypotension, haemorrhage control and haemostatic resuscitation. Massive transfusion protocols improve survival in severely injured patients. Early recognition that the patient will need massive blood transfusion will limit the use of crystalloids. Initially during resuscitation, fresh frozen plasma, packed red blood cells (PRBCs and platelets should be transfused in the ratio of 1:1:1 in severely injured patients. Fresh whole blood can be an alternative in patients who need a transfusion of 1:1:1 thawed plasma, PRBCs and platelets. Close monitoring of bleeding and point of care coagulation tests are employed, to allow goal-directed plasma, PRBCs and platelets transfusions, in order to decrease the risk of transfusion-related acute lung injury.

  3. Post-transfusion and maternal red blood cell alloimmunization in Uganda

    NARCIS (Netherlands)

    Natukunda, Bernard

    2013-01-01

    Over the last two decades, there has been substantial progress in the area of blood safety in Uganda. In contrast, little attention has been paid to transfusion safety in Uganda and there are gaps in laboratory and clinical transfusion practices within hospitals. Assessment of the current practice a

  4. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

    Science.gov (United States)

    de Montalembert, Mariane; Ribeil, Jean-Antoine; Brousse, Valentine; Guerci-Bresler, Agnes; Stamatoullas, Aspasia; Vannier, Jean-Pierre; Dumesnil, Cécile; Lahary, Agnès; Touati, Mohamed; Bouabdallah, Krimo; Cavazzana, Marina; Chauzit, Emmanuelle; Baptiste, Amandine; Lefebvre, Thibaud; Puy, Hervé; Elie, Caroline

    2017-01-01

    The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation. PMID:28257476

  5. High multi-cytokine levels are not a predictive marker of alloimmunization in transfused sickle cell disease patients.

    Science.gov (United States)

    Tatari-Calderone, Zohreh; Fasano, Ross M; Miles, Megan R; Pinto, Ligia A; Luban, Naomi L C; Vukmanovic, Stanislav

    2014-07-01

    Patients with sickle cell disease (SCD) receive multiple red blood cell (RBC) transfusions for both prevention of and therapy for disease-related complications. In some patients, transfusion results in development of both allo- and auto-antibodies to RBC antigens. What precipitates the antibody formation is currently unclear. It has been hypothesized that a pro-inflammatory state preceding the therapeutic transfusion may be a predisposing factor. Plasma levels of ten cytokines were evaluated upon recruitment to the study of 83 children with SCD undergoing therapeutic RBC transfusions. The levels of cytokines were correlated with development of anti-RBC antibodies prior, or during seven years post recruitment. Twelve subjects displayed significantly higher levels of all cytokines examined, with pro-, as well as anti-inflammatory properties. Surprisingly, the elevated levels of cytokines were preferentially found in patients without anti-RBC allo- and/or auto-antibodies. Further, presence of high cytokine levels was not predictive of anti-RBC antibody development during the subsequent seven year follow up. These data suggest that the increased concentration of multiple cytokines is not a biomarker of either the presence of or susceptibility to the development of RBC alloimmunization.

  6. Establishment of Adoptive Immunotherapy Transfusion Time of Cytokine-induced Killer Cells

    Institute of Scientific and Technical Information of China (English)

    Wu Changping; Deng Haifeng; Jiang Jingting

    2013-01-01

    Objective:To investigate the variation of immunophenotype and cytotoxic activity of autologous cytokine-induced killer (CIK) cells in patients with malignant tumors, and explore the best time of adoptive immunotherapy infusion of CIK cells. Methods:Peripheral blood mononuclear cells (PBMC) in 40 patients with malignant tumors were collected and cultivated into CIK cells in vitro by biotechnology under induction of several kinds of cytokines including interferon γ (IFN-γ), recombinant human interleukin 1α (rhIL-1α), CD3 monoclonal antibody (CD3McAb) and recombinant human interleukin 2 (rhIL-2). Immunophenotypes were dynamically monitored by lfow cytometry (FCM), and cytotoxic activity was analyzed by methyl thiazolyl tetrazolium (MTT) method. Results:After induction and expansion at different time, CD3+, CD3+CD8+and CD3+CD56+in mononuclear cells (MNC) had an up-regulated tendency. CD3+CD4+reached the peak on day 7, and then decreased slowly;CD25 reached the peak in earlier period of cultivation (3-7 days), and decreased slowly in 7-14 days, and then decreased rapidly in 14-21 days. Human leukocyte antigen DR (HLA-DR) was on the rise in 0-14 days, and decreased rapidly after reaching the peak on day 14. The cytotoxic activity of mature CIK cells was signiifcantly higher than that of non-activated PBMC, and the difference was statistically signiifcant (P Conclusion:PBMC can be induced into typical CIK cells for about 14 days when CD3+CD56+cells are at the logarithmic phase. The best time of CIK cell adoptive immunotherapy transfusion for the patients with malignant tumors is on day 14.

  7. Safety, tolerability, and outcomes of regular automated red cell exchange transfusion in the management of sickle cell disease.

    Science.gov (United States)

    Tsitsikas, Dimitris A; Sirigireddy, Bala; Nzouakou, Ruben; Calvey, Alexander; Quinn, Joanne; Collins, Janine; Orebayo, Funmilayo; Lewis, Natasha; Todd, Sophie; Amos, Roger J

    2016-12-01

    We report here our experience with regular automated red cell exchange transfusion for the management of chronic complications of sickle cell disease in 50 patients in our institution from June 2011 to December 2014. The mean sickle hemoglobin level was 44% and 8.5% pre- and post-transfusion, respectively. Platelets were reduced by a mean 70% during the procedure with a count of less than 50 × 10(9) /l in 6% of cases. The alloimmunization rate was 0.065/100 units of red cells with no hemolytic reactions. Patients with no iron overload at baseline showed no evidence of iron accumulation with a mean liver iron concentration of 1.6 mg/g dry tissue and 1.9 mg/g dry tissue at baseline and 36 months, respectively. All six patients with pre-existing iron overload and on chelation therapy, showed a gradual reduction of their liver iron concentration and two patients could discontinue chelation during the follow-up period. Seventy percentage of patients who were on the programme for recurrent painful crises showed a sustained reduction in the number of emergency hospital attendances; the mean number of days in hospital for emergency treatment was 103 in the year prior to commencing ARCET and reduced to 62 (40%) after the first 12 months, 51 (50%) after 24 months, and 35 days (66%) after 36 months. J. Clin. Apheresis 31:545-550, 2016. © 2015 Wiley Periodicals, Inc.

  8. Cryopreserved red blood cells for pediatric transfusion. Frozen storage of small aliquots in polyvinyl chloride (PVC) plastic bags.

    Science.gov (United States)

    Valeri, C R; Valeri, D A; Gray, A; Melaragno, A J; Vecchione, J J; Dennis, R C; Emerson, C P

    1981-01-01

    Human nonrejuvenated and rejuvenated red bood cells were prepared for cryopreservation and subsequent pediatric transfusion. Glycerol was added to the red blood cells in the primary polyvinyl chloride plastic collection bag to achieve a concentration of 40 per cent W/V. The red blood cells were concentrated by centrifugation, and the supernatant glycerol was discarded. Each glycerolized unit was divided into four equal aliquots in the individual 600-ml bags of a dry quadruple polyvinyl chloride plastic system, and each aliquot was frozen and stored at -80 C. After thawing, sodium chloride solutions were used to wash the aliquots in the IBM Blood Processor 2991-1 or 2991-2 or the Haemonetics Blood Processor 115, and the washed aliquots were stored in a sodium chloride-glucose-phosphate solution at 4 C for 24 hours. Freeze-thaw recovery of the red blood cells was about 97 per cent, and freeze-thaw-wash recovery was about 84 per cent. Twenty-four-hour posttransfusion survival values were about 92 per cent for both nonrejuvenated and indated-rejuvenated red blood cells. Nonrejuvenated red blood cells, those frozen within three to five days of collection without biochemical modification, had normal oxygen transport function at the time of transfusion; rejuvenated red blood cells, those biochemically treated with PIGPA Solution A after three to five days of storage at 4 C, had improved oxygen transport function at the time of transfusion.

  9. Focal Adhesion-Independent Cell Migration.

    Science.gov (United States)

    Paluch, Ewa K; Aspalter, Irene M; Sixt, Michael

    2016-10-06

    Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion-independent migration, and highlight the remaining open questions for the future.

  10. Infusion pumps and red blood cell damage in transfusion therapy: an integrative revision of the academic literature 1

    Science.gov (United States)

    Wilson, Ana Maria Miranda Martins; Peterlini, Maria Angélica Sorgini; Pedreira, Mavilde da Luz Gonçalves

    2016-01-01

    ABSTRACT Objectives: to obtain information from scientific literature concerning infusion pumps used in administering erythrocyte (red blood cells) and to evaluate the implications in the practical use of this equipment by nurses when conducting transfusions. Method: an integrative revision of the following scientific databases: Pubmed/Medline, Scopus, the Virtual Library for Health, SciELO, Web of Science and Cochrane. The following descriptors were used: "infusion pumps", "blood transfusion", "transfused erythrocyte" and "hemolyis". There were no restrictions on the scope of the initial data and it was finalized in December 2014. 17 articles were identified in accordance with the inclusion and exclusion criteria. Results: all of the publications included in the studies were experimental in vitro and covered the use of infusion pumps in transfusion therapy. A summary of the data was presented in a synoptic chart and an analysis of it generated the following categories: cellular damage and the infusion mechanism. Conclusion: infusion pumps can be harmful to erythrocytes based on the infusion mechanism that is used, as the linear peristaltic pump is more likely to cause hemolysis. Cellular damage is related to the plasmatic liberation of markers that largely dominate free hemoglobin and potassium. We reiterate the need for further research and technological investments to guide the development of protocols that promote safe practices and that can contribute to future clinical studies. PMID:27533272

  11. Infusion pumps and red blood cell damage in transfusion therapy: an integrative revision of the academic literature

    Directory of Open Access Journals (Sweden)

    Ana Maria Miranda Martins Wilson

    Full Text Available ABSTRACT Objectives: to obtain information from scientific literature concerning infusion pumps used in administering erythrocyte (red blood cells and to evaluate the implications in the practical use of this equipment by nurses when conducting transfusions. Method: an integrative revision of the following scientific databases: Pubmed/Medline, Scopus, the Virtual Library for Health, SciELO, Web of Science and Cochrane. The following descriptors were used: "infusion pumps", "blood transfusion", "transfused erythrocyte" and "hemolyis". There were no restrictions on the scope of the initial data and it was finalized in December 2014. 17 articles were identified in accordance with the inclusion and exclusion criteria. Results: all of the publications included in the studies were experimental in vitro and covered the use of infusion pumps in transfusion therapy. A summary of the data was presented in a synoptic chart and an analysis of it generated the following categories: cellular damage and the infusion mechanism. Conclusion: infusion pumps can be harmful to erythrocytes based on the infusion mechanism that is used, as the linear peristaltic pump is more likely to cause hemolysis. Cellular damage is related to the plasmatic liberation of markers that largely dominate free hemoglobin and potassium. We reiterate the need for further research and technological investments to guide the development of protocols that promote safe practices and that can contribute to future clinical studies.

  12. Blood transfusions

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000431.htm Blood transfusions To use the sharing features on this ... several sources of blood which are described below. Blood From the Public (Volunteer Blood Donation) The most ...

  13. Alloimmunization screening after transfusion of red blood cells in a prospective study Pesquisa de aloimunização após transfusão de concentrados de hemácias em um estudo prospectivo

    Directory of Open Access Journals (Sweden)

    Vitor Mendonça Alves

    2012-01-01

    Full Text Available BACKGROUND: Several irregular red blood cell alloantibodies, produced by alloimmunization of antigens in transfusions or pregnancies, have clinical importance because they cause hemolysis in the fetus and newborn and in transfused patients. OBJECTIVE: a prospective analysis of patients treated by the surgical and clinical emergency services of Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (HC/UFTM, Brazil was performed to correlate alloimmunization to clinical and epidemiological data. METHODS: Blood samples of 143 patients with initial negative antibody screening were collected at intervals for up to 15 months after the transfusion of packed red blood cells. Samples were submitted to irregular antibody testing and, when positive, to the identification and serial titration of alloantibodies. The Fisher Exact test and Odds Ratio were employed to compare proportions. RESULTS: Fifteen (10.49% patients produced antibodies within six months of transfusion. However, for 60% of these individuals, the titers decreased and disappeared by 15 months after transfusion. Anti-K antibodies and alloantibodies against antigens of the Rh system were the most common; the highest titer was 1:32 (anti-K. There was an evident correlation with the number of transfusions. CONCLUSIONS: Given the high incidence of clinically important red blood cell alloantibodies in patients transfused in surgical and clinical emergency services, we suggest that phenotyping and pre-transfusion compatibilization for C, c, E, e (Rh system and K (Kell system antigens should be extended to all patients with programmed surgeries or acute clinical events that do not need emergency transfusions.OBJETIVO: Vários aloanticorpos irregulares antieritrocitários, produzidos por sensibilizações a antígenos estranhos durante gestações ou transfusões, possuem importância clínica por provocarem hemólise no feto ou recém-nascido e/ou no receptor de sangue. Diante

  14. Side Effects during Treatment of Advanced Gastric Carcinoma by Chemotherapy Combined with CIK-cell Transfusion in Elderly People

    Institute of Scientific and Technical Information of China (English)

    Jingting Jiang; Changping Wu; Liangrong Shi; Ning Xu; Haifeng Deng; Mingyang Lu; Mei Ji; Yibei Zhu; Xueguang Zhang

    2008-01-01

    OBJECTIVE To study the side effects and therapeutic results of autologous cytokine-induced killer (CIK) cell treatment in elderly patients with advanced gastric cancer.METHODS CIK cells were induced and cultured using biotechnics in vitro, and then the ceils were infused back into the patients. Sixty elderly gastric cancer patients treated by chemotherapy (FOLFOX4 protocol) were followed-up. Among them, 29 patients were treated with CIK cells during application of chemotherapy. Short-term curative effects and adverse events from the CIK transfusion and chemotherapy were observed.RESULTS Eight cases developed partial remission (PR), 9 cases moderate remission (MR), 7 cases stable disease(SD) and 5 cases progressive disease (PD). Out of a total of 29 patients who received chemotherapy combined with autologous CIK therapy,the total remission rate (PR + MR) was 58.6%. The total remission rate following chemotherapy alone was 45.2%, including 5 PR cases, 9 MR cases, 7 SD cases, and 10 PD cases. There was a relatively lower rate of severe chemotherapic toxicities in the CIK-cell transfusion group. Side effects of autologous CIK transfusion included chilis (13 cases), fever (9 cases), nausea and vomiting(1 case) and general malaise (3 cases). Side effects were treated with conventional therapy resulting in their amelioration. No patients developed shock, blood capillary leakage syndrome, or abnormalities in routine blood, urine, liver and renal function tests.CONCLUSION Adoptive immunotherapy with autologous CIK cells may decrease the clinical signs and symptoms of elderly patients who suffer from advanced gastric cancer. Adverse reactions of patients can be alleviated by conventional therapy.Autologous CIK-cell transfusion may improve endurance to chemotherapy.

  15. Transfusion Medicine

    Directory of Open Access Journals (Sweden)

    Smit Sibinga CT

    2013-07-01

    Full Text Available Cees Th. Smit Sibinga ID Consulting, Zuidhorn, The NetherlandsTransfusion Medicine is a bridging science, spanning the evidence-based practice at the bedside with the social sciences in the community.     Transfusion Medicine starts at the bedside. Surprisingly, only recently that has become rediscovered with the development of ‘patient blood management’ and ‘patient centered’ approaches to allow the growth of an optimal and rational patient care through supportive hemotherapy – safe and effective, affordable and accessible.1    Where transfusion of blood found its origin in the need of a patient, it has drifted away for a long period of time from the bedside and has been dominated for almost a century by laboratory sciences. At least the first ten editions of the famous and well reputed textbook Mollison’s Blood Transfusion in Clinical Medicine contained only a fraction on the actual bedside practice of transfusion medicine and did not focus at all on patient blood management.2    This journal will focus on all aspects of the transfusion chain that immediately relate to the bedside practice and clinical use of blood and its components, and plasma derivatives as integral elements of a human transplant tissue. That includes legal and regulatory aspects, medical, ethical and cultural aspects, pure science and pathophysiology of disease and the impact of transfusion of blood, as well as aspects of the epidemiology of blood transfusion and clinical indications, and cost-effectiveness. Education through timely and continued transfer of up to date knowledge and the application of knowledge in clinical practice to develop and maintain clinical skills and competence, with the extension of current educational approaches through e-learning and accessible ‘apps’ will be given a prominent place.

  16. Mechanisms of severe transfusion reactions.

    Science.gov (United States)

    Kopko, P M; Holland, P V

    2001-06-01

    Serious adverse effects of transfusion may be immunologically or non-immunologically mediated. Currently, bacterial contamination of blood products, particularly platelets, is one of the most significant causes of transfusion-related morbidity and mortality. Septic transfusion reactions can present with clinical symptoms similar to immune-mediated hemolytic transfusion reactions and transfusion-related acute lung injury. Extremely high fever and/or gastrointestinal symptoms, in a transfusion recipient, may be indicative of sepsis. The diagnosis is based upon culturing the same organism from both the patient and the transfused blood component. Numerous organisms have been implicated as the cause of septic transfusion reactions. Due to different storage conditions, gram negative organisms are more often isolated from red blood cell components; gram positive organisms are more often isolated from platelets. Prevention of septic transfusion reactions is primarily dependent on an adequate donor history and meticulous preparation of the donor phlebotomy site. Visual inspection of blood components prior to transfusion is also vital to preventing these reactions. Several methods of detection of bacterial contamination and inactivation of pathogens are currently under active investigation.

  17. Geographic Variability in Potentially Discretionary Red Blood Cell Transfusions After Coronary Artery Bypass Grafting Surgery

    Science.gov (United States)

    Likosky, Donald S.; Al-Attar, Paul M.; Malenka, David J.; Furnary, Anthony P.; Lehr, Eric J.; Paone, Gaetano; Kommareddi, Mallika; Helm, Robert; Jin, Ruyun; Maynard, Chuck; Hanson, Eric C.; Olmstead, Elaine M.; Mackenzie, Todd A.; Ross, Cathy S.; Zhang, Min

    2016-01-01

    We assessed regional differences in potentially discretionary [coronary artery bypass (CABG) surgery. Regional variation in overall RBC rates remained after risk adjustment, perhaps due to differences in regional practice environments. Objective A number of established regional quality improvement collaboratives have partnered to assess and improve care across their regions under the umbrella of the “Cardiac Surgery Quality IMPROVEment (IMPROVE) Network”. The first effort of the IMPROVE Network has been to assess regional differences in potentially discretionary [coronary artery bypass (CABG) surgery across 56 medical centers in four IMPROVE Network regions between January 2008 and June 2012. Each center submitted the most recent 200 patients who received 0, 1, or 2 units of RBC transfusion during the index admission. Patient and disease characteristics, intra-operative practices, and percentage of cases receiving RBC transfusions were collected. Region-specific transfusion rates were calculated, after adjusting for pre- and intra-operative factors among region-specific centers. Results There were small, but significant, differences in patient case mix across regions. RBC transfusions of 1 or 2 units occurred among 25.2% (2,826/11,200) of CABG procedures. Significant variation in use and number of RBCs existed across regions [None: 74.8% (min:max 70.0%, 84.1%), 1 unit: 9.7% (5.1%, 11.8%), 2 units: 15.5% (9.1%, 18.2%)], p<0.001. Variation in overall transfusion rates remained after adjustment (9.1% – 31.7%, p<0.001). Conclusions Delivery of small volumes of RBC transfusions was common, yet varied across geographic regions. These data suggest that differences in regional practice environments, including transfusion triggers and anemia management, may contribute to variability in RBC transfusion rates. PMID:25227699

  18. PARENTERAL IRON SUCROSE AS AN ALTERNATIVE TO PACKED CELLS/BLOOD TRANSFUSION IN MODERATE-TO-SEVERE ANAEMIA IN PREGNANCY

    Directory of Open Access Journals (Sweden)

    Rama Sarala

    2016-03-01

    Full Text Available AIM This case study focuses on the efficacy of iron sucrose in moderate-to-severe anaemia in pregnancy and to compare the efficacy of iron sucrose with packed cell transfusion and based on the study to establish whether iron sucrose could be an alternative to packed cells transfusion for the management of moderate-to-severe anaemia complicating pregnancy remote from the term gestation. MATERIALS AND METHODS It is a case control study for a period of 2 years. Women were randomly selected where for the study group 50 patients intravenous iron sucrose was given and for control group 50 patients packed cells transfusion was given. RESULTS The study group and the control group had 50 subjects each. On an average 80% were in the age group of 15-24 yrs. in both groups. In both groups, on an average 85% were with moderate anaemia (6-8 g/dL and 15% were with severe anaemia (<6 g/dL. Mean requirement of iron sucrose for moderate anaemia was 1100 mg and for severe anaemia it was 1300 mg. Mean requirement of packed cells for moderate anaemia was 3 units and for severe anaemia 4-5 units. In iron sucrose group, mean haemoglobin% at baseline 7.1±0.8 g/dL, after 1 week 7.9±0.6, after 4 weeks 11±0.5 g/dL and at delivery 11.7±0.6 g/dL. In packed cells group, mean haemoglobin% at baseline 7.0±0.7 g/dL, after 1 week 10.2±0.5 g/dL, after 4 weeks 10.3±0.5 g/dL and at delivery 10.4±0.4 g/dL. The mean haematocrit values in iron sucrose group at baseline 20.9±2.5%, after 1 week 25.3±2.2% and after 4 weeks 33.6±2.0%. The mean haematocrit values in packed cells group at baseline 20.8±2.3%, after 1 week 30.0±1.9% and after 4 weeks 30.2±2.0%. Mean rise of haematocrit from baseline to 1 week in iron sucrose and packed cells group were 4.4±1.3% and 9.1±2.0% respectively. Mean rise of haematocrit from baseline to 4 weeks in iron sucrose and packed cell group were 12.7±2.1% and 9.3±2.3 respectively. The mean ferritin values in iron sucrose group at baseline

  19. Solid Phase Red Cell Adherence Assay: a tubeless method for pretransfusion testing and other applications in transfusion science.

    Science.gov (United States)

    Ching, Eric

    2012-06-01

    Solid Phase Red Cell Adherence Assay (SPRCA) is one of the two tubeless methods developed to improve sensitivity and specificity in blood group serology. The SPRCA (solid phase) and the column agglutination (gel) technology have gained wide acceptance following successful adaptation to fully automated platforms, The purpose of this paper is to discuss the development, principle, procedures as well as laboratory and clinical applications of the SPRCA in transfusion medicine.

  20. Transfusão de hemácias em terapia intensiva: controvérsias entre evidências Red blood cell transfusion in the intensive care setting: controversies amongst evidence

    Directory of Open Access Journals (Sweden)

    Rubens Carmo Costa Filho

    2009-08-01

    com hemoglobina superiores a 7 g/dL. Não existe um consenso sobre o limiar transfusional em pacientes críticos. Os pacientes com doença cardiovascular parecem apresentar um maior risco de morte do que aqueles sem doença cardiovascular, para qualquer nível de hemoglobina. A transfusão guiada por níveis de hemoglobina e parâmetros fisiológicos, oxi-hemodinâmicos individualizados e contexto clínico parece ser atualmente estratégia mais aceita do que a correção arbitrária e isolada da hemoglobina.Anemia is a prevalent issue in intensive care units. It appears in the first days, and may continue or worsen during hospital stay. Its etiology is generally multifactorial. Red blood cell transfusion is the most common intervention for treating anemia. Approximately 12 million blood units are used for transfusions in the United States, 25% to 30% in the intensive care units. Due to reduction of transfusion infections the increased safety has allowed an expansion of clinical indications. However, transfusion therapy is associated with other adverse effects such as nosocomial infections, immunological impairment, lung injury, hemolytic reactions and higher cancer incidence. Various papers have tried to show an association between correction of anemia and mortality-morbidity, but no consensus has been reached in literature. One of the current World Health Organization's proposals is to reduce potentially unnecessary transfusions, promoting a rational transfusion attitude. The primary objective of this narrative review is to approach controversies regarding the transfusion threshold according to recent studies, and as a secondary objective, it aims to discuss iatrogenic anemia aspects and the different behaviors among intensivists on the best practices for implementation of transfusion practices. It is not within our objectives to discuss transfusion complications, although they are mentioned. A search was conducted on electronic literature databases (Pub

  1. Truth about Transfusions (For Kids)

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? The Truth About Transfusions KidsHealth > For Kids > The Truth About Transfusions A A A Every year, more ... loss, or have a certain disease, such as cancer or sickle cell anemia. Little babies that are ...

  2. Transfusion strategy

    DEFF Research Database (Denmark)

    Jakobsen, Carl-Johan

    2014-01-01

    Blood transfusion is associated with increased morbidity and mortality and numerous reports have emphasised the need for reduction. Following this there is increased attention to the concept of patient blood management. However, bleeding is relatively common following cardiac surgery and is furth....... In conclusion the evidence supports that each institution establishes its own patient blood management strategy to both conserve blood products and maximise outcome.......Blood transfusion is associated with increased morbidity and mortality and numerous reports have emphasised the need for reduction. Following this there is increased attention to the concept of patient blood management. However, bleeding is relatively common following cardiac surgery and is further...

  3. Factors affecting invalid red blood cell transfusion and countermeasures%红细胞输注无效的影响因素及对策

    Institute of Scientific and Technical Information of China (English)

    刘默; 杜瑜; 周宏伟; 刘芳; 彭朝津

    2012-01-01

    目的 探讨影响临床红细胞输注无效的因素,并就红细胞输注无效影响因素提出相应的临床对策.方法 采用回顾性分析的方法对2009年9月至2011年9月在解放军总医院第一附属医院血液科926份红细胞输注病例的临床资料进行整理和分析,分析临床红细胞输注无效的影响因素.结果 926份红细胞输注病例共输注红细胞1289次,194次为无效输注,无效输注率达到15.05%;而二分类Logistic回归分析发现:多次输血、多次妊娠、患有2种以上自身免疫系统疾病及红细胞制品的贮存时间长是影响红细胞输注效果的因素.结论 红细胞输注无效率较高,在临床工作中,严格掌握红细胞输注适应症,并采取针对性预防措施,可有效避免红细胞输注无效的发生.%Objective To investigate the clinical factors affecting RBC transfusion,and invalid red blood cell transfusion corresponding clinical counter measures. Methods A retrospective analysis of September 2009 - September 2011 Department of Hematology in our hospital 926 cases of red blood cell transfusion clinical data collation, analysis of clinical factors affecting red blood cell transfusion. Results A total of 926 patients were given red blood cell transfusion 1289 times, 194 times invalid infusion, invalid infusion rate 15.05% ;And two Logistic Regression analysis;multiple transfusions, multiple pregnancies,with 2 or more autoimmune diseases and red blood cell products storation time are factors affecting red blood cell transfusion. Conclusions Invalid red blood cell transfusion rate is high, in clinical work,strict control of red blood cell transfusion indications and take appropriate preventive measures can effectively prevent the occurrence of red blood cell transfusion.

  4. Use of Esophageal Hemoximetry to Assess the Effect of Packed Red Blood Cell Transfusion on Gastrointestinal Oxygenation in Newborn Infants.

    Science.gov (United States)

    Vora, Farha M; Gates, Judy; Gerard, Kimberley; Hanson, Shawn; Applegate, Richard L; Blood, Arlin B

    2017-01-18

    Objectives There are no widely accepted methods of continuously monitoring gut oxygenation in the newborn during packed red blood cell transfusion. We investigated the use of an orally inserted light spectroscopy probe to measure lower esophageal oxyhemoglobin saturations (eStO2) before, during, and after transfusion and made comparisons with abdominal near-infrared spectroscopy (NIRS) and superior mesenteric artery (SMA) flow. Study Design Thirteen neonates with corrected gestational ages ranging from 22 weeks, 0 day to 37 weeks, 5 days were enrolled. eStO2 and NIRS measurements were recorded continuously for a 25-hour period starting 1 hour prior to starting the 4-hour transfusion. Transabdominal ultrasound was used to measure SMA flow prior to, upon completion, and 20 hours after the transfusion. Results Twelve infants completed the study. eStO2 was well-tolerated and was weakly (r = 0.06) correlated (p < 0.001) with NIRS. Compared with NIRS, eStO2 demonstrated a markedly greater variation in oxyhemoglobin values. NIRS and SMA flow measurements did not change, while eStO2 increased from 48 ± 5% and 45 ± 5% in the pre- and intratransfusion periods to 57 ± 4% in the posttransfusion period (p = 0.03). Conclusion Measurement of eStO2 is feasible in neonates and may provide a continuous and sensitive index of rapid changes in mesenteric oxygenation in this patient population.

  5. Neonatal transfusion practices

    NARCIS (Netherlands)

    Lindern, Jeannette Susanne von

    2011-01-01

    Red blood cells (RBCs) are probably the most frequently used drug given to very preterm infants; more than 90% of infants with a birth weight <1000 grams receive one or more RBC transfusions. Except for reduction of the amount of blood drawn for laboratory tests and use of a single donor program, no

  6. Metabolomics in transfusion medicine.

    Science.gov (United States)

    Nemkov, Travis; Hansen, Kirk C; Dumont, Larry J; D'Alessandro, Angelo

    2016-04-01

    Biochemical investigations on the regulatory mechanisms of red blood cell (RBC) and platelet (PLT) metabolism have fostered a century of advances in the field of transfusion medicine. Owing to these advances, storage of RBCs and PLT concentrates has become a lifesaving practice in clinical and military settings. There, however, remains room for improvement, especially with regard to the introduction of novel storage and/or rejuvenation solutions, alternative cell processing strategies (e.g., pathogen inactivation technologies), and quality testing (e.g., evaluation of novel containers with alternative plasticizers). Recent advancements in mass spectrometry-based metabolomics and systems biology, the bioinformatics integration of omics data, promise to speed up the design and testing of innovative storage strategies developed to improve the quality, safety, and effectiveness of blood products. Here we review the currently available metabolomics technologies and briefly describe the routine workflow for transfusion medicine-relevant studies. The goal is to provide transfusion medicine experts with adequate tools to navigate through the otherwise overwhelming amount of metabolomics data burgeoning in the field during the past few years. Descriptive metabolomics data have represented the first step omics researchers have taken into the field of transfusion medicine. However, to up the ante, clinical and omics experts will need to merge their expertise to investigate correlative and mechanistic relationships among metabolic variables and transfusion-relevant variables, such as 24-hour in vivo recovery for transfused RBCs. Integration with systems biology models will potentially allow for in silico prediction of metabolic phenotypes, thus streamlining the design and testing of alternative storage strategies and/or solutions.

  7. Fluid shift from intravascular compartment during fetal red blood cell transfusion

    NARCIS (Netherlands)

    Kamping, M.A.; Pasman, S.A.; Bil-van den Brink, C.P.; Oepkes, D.; Adama van Scheltema, P.N.; Vandenbussche, F.P.H.A.

    2013-01-01

    OBJECTIVES: Intrauterine transfusion imposes a considerable burden on the fetal circulation by increasing volume and pressure, and a fluid shift from the fetal circulation occurs even during the procedure. The aim of this study was to quantify the intraprocedural fluid shift and to investigate the e

  8. PHYSIOLOGIC TRANSFUSION TRIGGERS AND MASSIVE TRANSFUSION

    OpenAIRE

    Tánczos Krisztián; Molnár Zsolt

    2013-01-01

    Blood transfusion is often a life saving intervention, but can also be harmful. Restrictive transfusion protocols have recently been developed with a post transfusion target haemoglobin level of 70–100 g/l. Whether haemoglobin level on its own is enough to guide our transfusion policy is an important issue. This review was aimed to look at other possible, so called physiological indicators of blood transfusion what clinicians can be used in addition to haemoglobin during their everyday practi...

  9. Does blood transfusion affect pituitary gonadal axis and sperm parameters in young males with sickle cell disease?

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2013-01-01

    Full Text Available Objective: We evaluated the effect of packed red cell transfusion (PCTx on serum concentrations of gonadotropins luteinizing hormone and follicle-stimulating hormone (LH and FSH and testosterone (T levels and measured sperm parameters in young adults with sickle cell disease (SCD on top-up transfusion (TTx and those on exchange transfusion (ETx regimen. Materials and Methods: Basal serum concentrations of FSH, LH, and T and semen parameters were evaluated before and 7 days after PCTx in 18 young adults with transfusion-dependent SCD, aged 20.7 ± 2.88 years. They had full pubertal development (Tanner′s stage 5, and capacity to ejaculate. They were regularly transfused since early childhood. Chelation therapy was started early during the first 2 years of life using desferrioxamine and was replaced by deferasirox for the last 4-5 years. Ten patients were on TTx and eight were on ETx regimen. Results: PCTx significantly increased hemoglobin (Hb from 8.5 ± 1.17 g/dl to 10.5 ± 0.4 g/dl, T from 12.3 ± 1.24 nmol/L to 14.23 ± 1.22 nmol/L and gonadotropins′ concentrations. Sperm parameters improved significantly after PCTx including: total sperm count from 87.4 ± 24.6 million/ml to 146.2 ± 51.25 million/ml, total progressive sperm motility (TPM from 40.8 ± 11.1 million/ml to 93.4 ± 38.3 million/ml, rapid progressive sperm motility (RPM progressive motility from 29.26 ± 8.75 million/ml to 67.4 ± 29 million/ml. After PCTx the total sperm count, TPM and RPM were significantly better in the ETx group versus the TTx group. Before and after PCTx, T concentrations were correlated significantly with sperm total count, volume, TPM and RPM (r = 0.53, 0.55, 0.42, and 0.38, respectively, P < 0.01. Hb concentrations were correlated significantly with sperm count, TPM, RPM, and % of sperms with normal morphology (r = 0.60, 0.69, 0.66, and 0.86, respectively, P < 0.001. Conclusion: Our study suggests that in males with SCD blood transfusion is associated

  10. [Research advance on clinical blood transfusion and tumor therapy].

    Science.gov (United States)

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  11. Blood Transfusion (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Blood Transfusions KidsHealth > For Parents > Blood Transfusions A A ... and help put your child at ease. About Blood Transfusions Blood is like the body's transportation system. ...

  12. A method to collect, store and issue multiple aliquots of packed red blood cells for neonatal transfusions.

    Science.gov (United States)

    Strauss, R G; Villhauer, P J; Cordle, D G

    1995-01-01

    Premature neonates require multiple red blood cell (RBC) transfusions. Single-donor programs have been proposed as a means to limit donor exposures, but methods must be developed to collect, store long-term and issue multiple aliquots of RBCs from a single donor. We evaluated a method by which RBCs could be collected, leukocyte depleted, repeatedly centrifuged for issuance as multiple small aliquots of high-hematocrit cells and then resuspended for continued storage throughout 42 days. The quality of RBCs handled by the method were compared to cells stored in standard fashion. Leakage of intracellular potassium, hemoglobin and lactic dehydrogenase into the extracellular fluid from RBCs processed by either method was comparable-indicating maintenance of RBC integrity. Multiple cultures, taken throughout the period of storage, were sterile to document that extensive handling did not introduce contamination. This new method appears promising as a means to provide RBCs for neonates.

  13. Red cell storage age policy for patients with sickle cell disease: A survey of transfusion service directors in the United States.

    Science.gov (United States)

    Karafin, Matthew S; Singavi, Arun K; Irani, Mehraboon S; Puca, Kathleen E; Baumann Kreuziger, Lisa; Simpson, Pippa; Field, Joshua J

    2016-02-01

    In patients with sickle cell disease (SCD), the effects of the red cell storage lesion are not well defined. The objective of this study was to determine the prevalence of transfusion services that limit red cell units by storage age for patients with SCD. We developed a 22 question survey of transfusion service director opinions and their corresponding blood bank policies. Target subjects were systematically identified on the AABB website. Responses were recorded in SurveyMonkey and summarized using standard statistical techniques. Ninety transfusion service directors responded to the survey. Response rate was 22%. Only 23% of respondents had storage age policies in place for patients with SCD, even though 36% of respondents consider older units to be potentially harmful in this patient population. Of those with a policy, a less-than 15 day storage age requirement was most often used (75%), but practices varied, and most respondents (65%) agreed that evidence-based guidelines regarding storage age are needed for patients with SCD. Policies, practices and opinions about the risks of older units for patients with SCD vary. As patients with SCD may have unique susceptibilities to features of the red cell storage lesion, prospective studies in this population are needed to determine best practice.

  14. Postoperative red blood cell transfusion strategy in frail anemic elderly with hip fracture. A randomized controlled trial.

    Science.gov (United States)

    Gregersen, Merete

    2016-04-01

    Hip fracture in the elderly is associated with poor recovery from physical disability and mortality. Perioperative blood loss is common, and anemia might be fatal in the frail elderly. Red blood cell transfusions might increase the risk of infection. In an observational study, a liberal transfusion strategy with hemoglobin (Hb) target of 7 mmol/l (11.3 g/dl) seemed to improve survival in nursing home residents with hip fracture compared to the recommended restrictive strategy with a Hb target of 6 mmol/l (9.7 g/dl) according to the Danish Health Authority. Our aim was to compare these two strategies in the frail elderly in a randomized controlled trial on the outcomes: recovery from physical disabilities, mortality, infection, infection biomarkers, and overall Quality of Life (OQoL). We included 284 elderly admitted to hospital for surgical hip fracture repair from nursing homes or sheltered housing facilities. The anemic patients were assigned postoperatively to the liberal or the restrictive transfusion strategy. Randomization divided each transfusion group into two equal blocks with regard to type of the residence. Hb was measured daily during the first three postoperative days, at least once during the following 4-6 days, then at least once a week during the subsequent three weeks. The transfusions were administered according to group assignments, but no later than 24 hours after the Hb determination, one unit at a time, and no more than two units per day. The intervention lasted for 30 days after surgery. Outcome measurements were performed on days 10, 30, 90, and 365. Blinded assessors evaluated physical performance and OQoL. The liberal transfusion strategy did not improve recovery from physical disabilities, mortality, infection rate, or OQoL compared to the restrictive strategy. However, in nursing home residents, 90-day mortality rate (20%) following the liberal strategy was statistically significantly lower than that (36%) after the restrictive strategy

  15. Initiation and Regulation of Complement during Hemolytic Transfusion Reactions

    Directory of Open Access Journals (Sweden)

    Sean R. Stowell

    2012-01-01

    Full Text Available Hemolytic transfusion reactions represent one of the most common causes of transfusion-related mortality. Although many factors influence hemolytic transfusion reactions, complement activation represents one of the most common features associated with fatality. In this paper we will focus on the role of complement in initiating and regulating hemolytic transfusion reactions and will discuss potential strategies aimed at mitigating or favorably modulating complement during incompatible red blood cell transfusions.

  16. Impact of Early Blood Transfusion After Kidney Transplantation on the Incidence of Donor-Specific Anti-HLA Antibodies.

    Science.gov (United States)

    Ferrandiz, I; Congy-Jolivet, N; Del Bello, A; Debiol, B; Trébern-Launay, K; Esposito, L; Milongo, D; Dörr, G; Rostaing, L; Kamar, N

    2016-09-01

    Little is known about the impact of posttransplant blood transfusion on the sensitization of anti-HLA antibodies and the formation of donor-specific antibodies (DSAs). The aims of our study were to determine the 1-year incidence of DSAs (assessed using a solid-phase assay) and antibody-mediated rejection (AMR) in kidney transplant patients who had or had not received a blood transfusion during the first year after transplantation. Included were 390 non-HLA-sensitized patients who had received an ABO-compatible kidney transplant and had not previously or simultaneously received a nonkidney transplant. Overall, 64% of patients received a red blood cell transfusion within the first year after transplantation, most within the first month. The overall 1-year incidence of DSAs was significantly higher in patients that had undergone transfusion (7.2% vs. 0.7% in patients with no transfusion, p transfusion group (n = 15, 6%) compared with the nontransfusion group (n = 2, 1.4%; p = 0.04). Blood transfusion was an independent predictive factor for de novo DSA formation but not for AMR. Patients who had a transfusion and developed DSAs were more often treated with cyclosporin A (n = 10, 55.5%) rather than tacrolimus (n = 45, 19.4%; p = 0.0001). In conclusion, early posttransplant blood transfusion may increase immunological risk, especially in underimmunosuppressed patients.

  17. An overview of unresolved inherent problems associated with red cell transfusion and potential use of artificial oxygen carriers and ECO-RBC: current status/future trends.

    Science.gov (United States)

    Seghatchian, Jerard; de Sousa, Gracinda

    2007-12-01

    This manuscript deals with why we need alternatives to liquid stored RBC highlighting some of the unresolved inherent problems related to red cell storage lesion and their potential impacts on the clinical outcomes and transfusion complications. The promise of several potential alternatives to red cell transfusions such as: Perfluorocarbon; Modified Hb-based oxygen carriers and newer design of Hb-based oxygen carriers are reviewed. It is noteworthy to say that since the first introduction of these oxygen carriers, almost five decades ago, the only successful drive has been to prepare safer and more convenient oxygen carriers, for enhancing the quality of life of recipients and their usage, either as substitutes to red cell transfusion or even as the bridge, remains patchy. Moreover, as new products with better characteristics become available the older products from the competitors are withdrawn. Finally, the current progress on universal RBC, known as ECO-cells is highlighted and, in the future perspectives, some of the current efforts in making the red cells transfusion safer and more efficacious are briefly addressed.

  18. Impact of autologous blood transfusion on the use of pack of red blood cells in coronary artery bypass grafting surgery

    Directory of Open Access Journals (Sweden)

    Leonardo Leiria de Moura da Silva

    2013-06-01

    Full Text Available OBJECTIVE: To evaluate the impact of Cell Saver autologous blood transfusion system (CS on the use of packed red blood cells (pRBC in coronary artery bypass grafting (CABG surgery. METHODS: We carried out a retrospective cross-sectional study in 87 patients undergoing primary elective CABG with miniaturized cardiopulmonary bypass (miniCPB, divided in two groups: 44 without-CS and 43 with-CS. We investigated the necessity of absolute use and the volume of packed red blood cells (pRBC in each group, as well as cardiovascular risk factors, presurgical variables and intraoperative surgical parameters. All data were collected from medical records and there was no randomization or intervention on group selection. Statistical analysis was performed with Student t-test, Mann-Whitney U-test and χ² test, with a 5% significance level. RESULTS: There were no significant differences between the two groups in terms of cardiovascular risk factors and pre and intraoperative variables. Evaluating the absolute use of pRBC during surgery, there was a statistically significant difference (P=0.00008 between the groups without-CS (21/44 cases; 47.7% and with-CS (4/43 cases; 9.3%. There was also a statistically significant difference (P=0.000117 in the volumes of pRBC between the groups without-CS (198.651258.65ml and with-CS (35.061125.67ml. On the other hand, in the early postoperative period (up to 24h there was no difference regarding either the absolute use or the volumes of pRBC between both studied groups. CONCLUSION: Autologous erythrocyte transfusion with CS use reduces the use of intraoperative homologous pRBC in coronary artery bypass grafting surgeries associated with miniCPB.

  19. Transfusion associated circulatory overload

    Directory of Open Access Journals (Sweden)

    Naveen Agnihotri

    2014-01-01

    Full Text Available Transfusion associated circulatory overload (TACO is an established, but grossly under diagnosed and underreported complication of blood transfusion. We present the case of a 46-year-old diabetic and hypertensive patient admitted to our hospital for recurrent episodes of urinary retention. Over initial 3 days of the admission, the patient received multiple units of packed red blood cells (RBC and fresh frozen plasma, uneventfully. However, the patient developed signs and symptoms suggestive of TACO with only small amount of the 4 th unit of RBC. The patient had to be shifted to the Intensive Care Unit for further management of this complication. Etiology of TACO is more complex than a mere circulatory overload and is still not completely understood. TACO leads to a prolonged hospital stay and morbidity in the patients developing this complication. TACO thus needs to be suspected in patients at risk for this complication.

  20. The Association of Hemodilution and Transfusion of Red Blood Cells with Biochemical Markers of Splanchnic and Renal Injury During Cardiopulmonary Bypass

    NARCIS (Netherlands)

    Huybregts, Rien A. J. M.; de Vroege, Roel; Jansen, Evert K.; van Schijndel, Anne W.; Christiaans, Herman M. T.; van Oeveren, Willem

    2009-01-01

    BACKGROUND: Hemodilution is the main Cause of a low hematocrit concentration during cardiopulmonary bypass. This low hematocrit may be insufficient for optimal tissue oxygen delivery and often results in packed cell transfusion. Our objective in this study was to find a relationship between intraope

  1. Efeito da transfusão de concentrado de hemácias sobre parâmetros de inflamação e estresse oxidativo em pacientes criticamente enfermos Effect of red blood cell transfusion on parameters of inflammation and oxidative stress in critically ill patients

    Directory of Open Access Journals (Sweden)

    Samuel Diomário da Rosa

    2011-03-01

    Full Text Available INTRODUÇÃO: Transfusão de concentrado de hemácias é freqüentemente prescrita nas unidades de terapia intensiva. Durante muito tempo a transfusão de hemácias era vista como tendo benefícios clínicos óbvios. Entretanto nos últimos anos a prática de transfusão sanguínea tem sido examinada de uma forma mais cautelosa, levando a investigações a respeito dos benefícios transfusionais, incluindo aqui o fato de os efeitos imunomoduladores relacionados à transfusão podem aumentar o risco de morbimortalidade dos pacientes. OBJETIVOS: Avaliar o efeito da transfusão de concentrado de hemácias e sua relação com a produção de citocinas inflamatórias e dano oxidativo em pacientes criticamente enfermos admitidos em uma unidade de terapia intensiva. MÉTODOS: Foram analisados durante 6 meses, no ano de 2008, pacientes internados na unidade de terapia intenvia que realizaram transfusão de concentrado de hemácias. Foram analisados os níveis séricos pré e pós transfusionais de interleucina-6 (IL-6, proteínas carboniladas e substâncias reativas ao ácido tiobarbitúrico (TBARS. RESULTADOS: Houve diminuição dos níveis séricos de IL-6 pós-transfusionais e um aumento significativo tanto para TBARS quanto para proteínas carboniladas. No entanto não houve significância estatística entre os níveis séricos de IL-6, TBARS antes e após transfusão de concentrado de hemácias e a taxa de mortalidade. Contudo ocorreu significância da relação dos níveis pós transfusionais de proteínas carboniladas e mortalidade. CONCLUSÃO: Transfusão de concentrado de hemácias é associada a aumento dos marcadores de dano oxidativo e diminuição de IL-6 em pacientes criticamente enfermos.INTRODUCTION: Red blood cell transfusions are common in intensive care units. For many years, transfusions of red blood were thought to have obvious clinical benefits. However, in recent years, the risks and benefits of blood transfusions have been

  2. Integrin-independent movement of immune cells

    OpenAIRE

    Pinner, Sophie E; Sahai, Erik

    2009-01-01

    Cell motility requires the temporal and spatial coordination of the actin cytoskeleton with cell-matrix adhesions. Since their discovery more than 20 years ago, integrins have been at the center of cell-matrix adhesion research. Integrin-mediated adhesions link the actin network to the extracellular matrix and are commonly observed as cells migrate across rigid two-dimensional substrates. However, as more cell motility studies are being conducted in three-dimensional (3D) culture systems and ...

  3. Reduction of exposure to blood donors in preterm infants submitted to red blood cell transfusions using pediatric satellite packs

    Directory of Open Access Journals (Sweden)

    Cristina Lika Uezima

    2013-09-01

    Full Text Available OBJECTIVE: In preterm newborn infants transfused with erythrocytes stored up to 28 days, to compare the reduction of blood donor exposure in two groups of infants classified according to birth weight. METHODS: A prospective study was conducted with preterm infants with birth weight <1000g (Group 1 and 1000-1499g (Group 2, born between April, 2008 and December, 2009. Neonates submitted to exchange transfusions, emergency erythrocyte transfusion, or those who died in the first 24 hours of life were excluded. Transfusions were indicated according to the local guideline using pediatric transfusion satellite bags. Demographic and clinical data, besides number of transfusions and donors were assessed. . Logistic regression analysis was performed to determine factors associated with multiple transfusions. RESULTS: 30 and 48 neonates were included in Groups 1 and 2, respectively. The percentage of newborns with more than one erythrocyte transfusion (90 versus 11%, the median number of transfusions (3 versus 1 and the median of blood donors (2 versus 1 were higher in Group 1 (p<0.001, compared to Group 2. Among those with multiple transfusions, 14 (82% and one (50% presented 50% reduction in the number of blood donors, respectively in Groups 1 and 2. Factors associated with multiple transfusions were: birth weight <1000g (OR 11.91; 95%CI 2.14-66.27 and presence of arterial umbilical catheter (OR 8.59; 95%CI 1.94-38.13, adjusted for confounders. CONCLUSIONS: The efficacy of pediatrics satellites bags on blood donor reduction was higher in preterm infants with birth weight <1000g.

  4. Transfusão de sangue em terapia intensiva: um estudo epidemiológico observacional Blood transfusion in intensive care: an epidemiological observational study

    Directory of Open Access Journals (Sweden)

    José Rodolfo Rocco

    2006-09-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A transfusão de concentrado de hemácias (CHA é muito freqüente no centro de tratamento intensivo (CTI, mas as conseqüências da anemia nos pacientes gravemente enfermos ainda são obscuras. Os objetivos desse estudo foram avaliar a freqüência, as indicações, os limiares transfusionais e o prognóstico dos pacientes criticamente enfermos que receberam CHA. MÉTODO: Estudo prospectivo de coorte realizado no CTI médico-cirúrgico de um Hospital Universitário durante 16 meses. Foram coletados dados demográficos, clínicos e os relacionados a transfusão de CHA. Regressão logística binária foi utilizada após as análises univariadas. RESULTADOS: Dos 698 pacientes internados, 244 (35% foram transfundidos com CHA. Os pacientes clínicos e em pós-operatório de urgência foram mais transfundidos. Os limiares transfusionais foram: hematócrito = 22,8% ± 4,5% e hemoglobina = 7,9 ± 1,4 g/dL. Os pacientes transfundidos receberam em média 4,4 ± 3,7 CHA e apresentaram maior letalidade no CTI (39,8% versus 13,2%; p 5 unidades e escore SAPS II. CONCLUSÕES: A transfusão de CHA é freqüente no CTI, particularmente nos pacientes internados por problemas clínicos e após cirurgias de emergência, com internação prolongada, em VM e com cirrose hepática. O limiar transfusional observado foi mais baixo que aquele assinalado pela literatura. A transfusão de CHA foi associada com maior letalidade.BACKGROUND AND OBJECTIVES: Packed red blood cell (PRBC transfusion is frequent in intensive care unit (ICU. However, the consequences of anemia in ICU patients are poorly understood. Our aim was to evaluate the prevalence, indications, pre-transfusion hematocrit and hemoglobin levels, and outcomes of ICU patients transfused with PRBC. METHODS: Prospective cohort study conducted at a medical-surgical ICU of a teaching hospital during a 16-month period. Patients' demographic, clinical, laboratory and transfusion-related data

  5. [Blood components and good practices in transfusion].

    Science.gov (United States)

    Andreu, Georges

    2015-02-01

    Each year, more than three millions of blood components are transfused to more than five hundred thousand patients in France. The optimal use of blood components requires that physicians prescribing blood components master the clinical indications of red blood cells concentrates, platelet concentrates and fresh frozen plasma. In addition, physicians in charge of blood component prescription should provide adequate pre- and post-transfusion information to their patients. Compliance of blood components administration in patients with safety guidelines contributes as well to their optimal use. In addition, for each blood component transfused, a proper evaluation of its safety and its efficacy should be done. Finally, a regular evaluation of transfusion practice in hospital services were blood components are used, through audits made in cooperation with their blood component provider, either blood transfusion centre or the hospital blood bank, enables to appreciate the level of compliance with safety and clinical guidelines, and more globally how the transfusion process is mastered.

  6. Non-transfusion-dependent thalassemias.

    Science.gov (United States)

    Musallam, Khaled M; Rivella, Stefano; Vichinsky, Elliott; Rachmilewitz, Eliezer A

    2013-06-01

    Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration.

  7. Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells.

    Directory of Open Access Journals (Sweden)

    Eva Maria Weissinger

    2015-04-01

    Full Text Available Allogeneic stem cell transplantation (allo-HSCT is one of the curative treatments for hematologic malignancies, but is hampered by severe complications, such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD and infections. CD34-selcetion of stem cells reduces the risk of aGvHD, but also leads to increased infectious complications and relapse. Thus, we studied the efficacy, safety and feasibility of transfer of gene modified donor T-cells shortly after allo-HSCT in two clinical trials between 2002 and 2007 and here we compare the results to unmodified donor leukocyte transfusion (DLI. The aim of these trials was to provide patients with the protection of T-cells after T-cell-depleted allo-HSCT in the matched or mismatched donor setting with an option to delete transduced T-cells, if severe aGvHD occurred within the trial period. Donor-T-cells were transduced with the replication-deficient retrovirus SFCMM-3, expressing HSV-Tk and the truncated LNGFR for selection of transduced cells. Transduced cells were transfused either after day +60 (matched donors or on day +42 (haploidentical donors.Nine patients were included in the first trial (MHH; 2002 until 2007 2 were included in TK007 (2005-2009 and 6 serve as a control group for outcome after haploidentical transplantation without HSV-TK-transduced DLI. Three patients developed acute GvHD, two had grade I of the skin, one had aGvHD on day +131 (post-HSCT; +89 post-HSV-Tk DLI grade II, which was successfully controlled by ganciclovir (GCV. Donor chimerism was stabilized after transfusion of the transduced cells in all patients treated. Functionality of HSV-Tk gene expressing T-cells was shown by loss of bcr-abl gene expression as well as by control of cytomegalovirus-reactivation. To date, 6patients have relapsed and died, 2 after a second HSCT without T-cell depletion or administration of unmodified T-cells. Eleven patients (7 post-HSV-Tk DLI are alive and well to date.

  8. Transfusion of blood and blood products: indications and complications.

    Science.gov (United States)

    Sharma, Sanjeev; Sharma, Poonam; Tyler, Lisa N

    2011-03-15

    Red blood cell transfusions are used to treat hemorrhage and to improve oxygen delivery to tissues. Transfusion of red blood cells should be based on the patient's clinical condition. Indications for transfusion include symptomatic anemia (causing shortness of breath, dizziness, congestive heart failure, and decreased exercise tolerance), acute sickle cell crisis, and acute blood loss of more than 30 percent of blood volume. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Platelet transfusion is indicated to prevent hemorrhage in patients with thrombocytopenia or platelet function defects. Cryoprecipitate is used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy. Transfusion-related infections are less common than noninfectious complications. All noninfectious complications of transfusion are classified as noninfectious serious hazards of transfusion. Acute complications occur within minutes to 24 hours of the transfusion, whereas delayed complications may develop days, months, or even years later.

  9. Ventilator associated pneumonia and transfusion, is there really an association? (the NAVTRA study

    Directory of Open Access Journals (Sweden)

    Gonzalez Marco

    2006-07-01

    Full Text Available Abstract Background Anemic syndrome is a frequent problem in intensive care units. The most probable etiology is the suppression of the erythropoietin response due to the direct effects of cytokines, as well as frequent blood sampling. Transfusions are not free of complications, therefore transfusion reactions are estimated to occur in 2% of the total packed red blood cells (pRBCs transfused. In the past several years, several trials had tried to compare the restrictive with the more liberal use of transfusions, and they were found to be equally effective. Nosocomial pneumonia is the most common nosocomial infection in intensive care units; the prevalence is 47% with an attributive mortality of 33%. There are multiple risk factors for the development of nosocomial pneumonia. Colonization of the upper airways is the most important pathophysiological factor but there are other factors implicated like, sedation techniques, inappropriate use of antibiotics and recumbent positioning. A secondary analysis of the CRIT study describes transfusion therapy and its practices in the United States. They found that transfusion practice is an independent risk factor for the development of nosocomial pneumonia. Methods This is a multicenter, prospective cohort study in different intensive care units in Colombia. A total of 474 patients were selected who had more than 48 hours of mechanical ventilation. The primary objective is to try to demonstrate the hypothetical relationship between the use of transfusions and nosocomial pneumonia. Secondly, we will try to determine which other factors are implicated in the development of pneumonia in intensive care units and describe the incidence of pneumonia and transfusion practices. Discussion Ventilator associated pneumonia is a primary problem in the intensive care unit, multiple factors have been associated with its presence in this study we try to explore the possible association between pneumonia and transfusion

  10. Case report: massive postpartum transfusion of Jr(a+) red cells in the presence of anti-Jra.

    Science.gov (United States)

    Yuan, S; Armour, R; Reid, A; Abdel-Rahman, K F; Rumsey, D M; Phillips, M; Nester, T

    2005-01-01

    Jr(a) is a high-prevalence antigen. The rare Jr(a-) individuals can form anti-Jr(a) after exposure to the Jr(a) antigen through transfusion or pregnancy. The clinical significance of anti-Jr(a) is not well established. This study reports a case of a 31-year-old woman with a previously identified anti-Jr(a) who required massive transfusion of RBCs after developing life-threatening postpartum disseminated intravascular coagulopathy. Despite the emergent transfusion of 15 units of Jr(a) untested RBCs, she did not develop laboratory or clinical evidence of acute hemolysis. The patient's anti-Jr(a) had a pretransfusion titer of 4 and a monocyte monolayer assay (MMA) reactivity of 68.5% (reactivity > 5% is considered capable of shortening the survival of incompatible RBCs). The titer increased fourfold to 64 and the MMA reactivity was 72.5% on Day 10 posttransfusion. Review of laboratory data showed evidence of a mild delayed hemolytic transfusion reaction by Day 10 posttransfusion. Despite rare reports of hemolytic transfusion reactions due to anti-Jr(a) in the literature, most cases, including this one, report that this antibody is clinically insignificant or causes only mild delayed hemolysis. Clinicians should be advised to balance the risks of withholding transfusion with the small chance of significant hemolysis after transfusion of Jr(a+) RBCs in the presence of anti-Jr(a).

  11. Intraoperative transfusion of packed red blood cells in microvascular free tissue transfer patients: assessment of 30-day morbidity using the NSQIP dataset.

    Science.gov (United States)

    Kim, Bobby D; Ver Halen, Jon P; Mlodinow, Alexei S; Kim, John Y S

    2014-02-01

    Although often a life-saving therapeutic maneuver, there is minimal data available that details the effects of intraoperative packed red blood cell transfusion (IOT) after microvascular free tissue transfer. The National Surgical Quality Improvement Program database was queried to identify all patients who underwent microvascular free tissue transfer between 2006 and 2010. Multivariate logistic regression models were used to determine the association between intraoperative transfusion and outcomes. Upon bivariate and multivariate analyses, IOT was significantly associated with higher rates of overall complications (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.12-3.63), medical complications (OR, 3.35; 95% CI, 1.75-6.42), postoperative transfusion (OR, 6.02; 95% CI, 2.02-17.97), and reoperation (OR, 2.24; 95% CI, 1.24-4.04). IOT was not associated with either surgical complications or free flap loss. IOT significantly increases risk for adverse overall and medical complications. However, IOT was not associated with surgical complications or free flap loss. Transfusion practices in the operating room should be reevaluated to improve overall outcomes.

  12. Hemolytic Transfusion Reactions

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2011-12-01

    Full Text Available The prevalence of fatal hemolytic transfusion reactions (HTRs is approximately 1:200000 per unit. Acute HTRs occur during or within 24 h after administration of a blood product. Transfusion of incompatible red blood cells (RBCs, and, more rarely, of a large volume of incompatible plasma usually are the causative agents. Delayed HTRs are caused by a secondary immune response to an antigen on the donor’s RBCs. Different mechanisms lead to intra- and extravascular hemolysis, such as complete complement activation, phagocytosis of RBCs covered with C3b by macrophages after incomplete complement activation, or destruction of RBCs covered only with IgG by direct cell to cell contact with K cells. The clinical consequences of HTRs are triggered via several pathophysiological pathways. Formation of anaphylatoxins, release of cytokines causing a systemic inflammatory response syndrome, activation of the kinin system, the intrinsic clotting cascade and fibrinolysis result in hypotension, disseminated intravascular coagulation, diffuse bleeding, and disruption of microcirculation leading to renal failure and shock. In this review, the symptoms of HTR are introduced, laboratory investigations and treatment are described, and some recommendations for prevention are given. (Journal of Current Pediatrics 2011; 9: 127-32

  13. Blood Transfusions (For Teens)

    Science.gov (United States)

    ... many precautions to confirm a patient's and donor's blood are compatible before giving a transfusion. In almost every situation, the benefits of having a blood transfusion far outweigh the risks. The Red Cross ...

  14. GRID INDEPENDENT FUEL CELL OPERATED SMART HOME

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Mohammad S. Alam

    2003-12-07

    A fuel cell power plant, which utilizes a smart energy management and control (SEMaC) system, supplying the power need of laboratory based ''home'' has been purchased and installed. The ''home'' consists of two rooms, each approximately 250 sq. ft. Every appliance and power outlet is under the control of a host computer, running the SEMaC software package. It is possible to override the computer, in the event that an appliance or power outage is required. Detailed analysis and simulation of the fuel cell operated smart home has been performed. Two journal papers has been accepted for publication and another journal paper is under review. Three theses have been completed and three additional theses are in progress.

  15. Epidemiology of Massive Transfusion

    DEFF Research Database (Denmark)

    Halmin, Märit; Chiesa, Flaminia; Vasan, Senthil K;

    2016-01-01

    OBJECTIVE: There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mort...

  16. Anemia of prematurity : time for a change in transfusion management?

    NARCIS (Netherlands)

    Khodabux, Chantal Muriel

    2013-01-01

    In this thesis we investigated clinical effects of allogeneic red blood cell (RBC) transfusions in premature infants, different transfusion volumes in relation to neonatal outcome in premature infants and the use of autologous cord blood (CB) as an alternative for allogeneic transfusions. Despite th

  17. Clinical Practice Guidelines for Transfusion of Patients in Critical Condition.

    Directory of Open Access Journals (Sweden)

    Rafael Alejandro Gómez Baute

    2009-03-01

    Full Text Available Clinical Practice Guidelines for Transfusion of Patients in Critical Condition. We stress transfusion criteria (blood cells, platelets, granulocyte concentrations, plasma and cryoprecipitate, doses, diagnosis and treatment of post-transfusion reactions. It includes assessment guidelines focused on the most important aspects to be accomplished.

  18. Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A;

    2017-01-01

    BACKGROUND AND OBJECTIVES: There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum...... and a higher Hb in weeks 3-12. CONCLUSION: This pilot study shows that intravenous iron could be an attractive alternative to RBC transfusion in severe postpartum anaemia, and that a larger trial is needed and feasible....

  19. Effect of Plasma and Red Blood Cell Transfusions on Survival in Patients with Combat Related Traumatic Injuries

    Science.gov (United States)

    2007-10-01

    2006;46:2014–2027. 21. Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288:1499–1507. 22...N, Moore EE, Sauaia A, Kenny -Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient...is on acute mortality and does not represent effects on causes of mortality that occur beyond that point. We agree that the total amount of blood

  20. Storage time of intraoperative transfused allogeneic red blood cells is not associated with new-onset postoperative atrial fibrillation in cardiac surgery

    DEFF Research Database (Denmark)

    Gu, Jiwei; Skals, Regitze Kuhr; Torp-Pedersen, Christian

    2017-01-01

    BACKGROUND: Allogeneic red blood cell (RBC) transfusion has been associated with new-onset postoperative atrial fibrillation (POAF) following cardiac surgery. Prolonged storage time of RBC may increase the risk. The primary aim of the study was to evaluate whether the storage time of RBC is assoc......BACKGROUND: Allogeneic red blood cell (RBC) transfusion has been associated with new-onset postoperative atrial fibrillation (POAF) following cardiac surgery. Prolonged storage time of RBC may increase the risk. The primary aim of the study was to evaluate whether the storage time of RBC...... is associated with development of POAF. MATERIALS AND METHODS: Pre-, per- and postoperative data were retrieved from the Western Denmark Heart Registry and local blood banks regarding patients who underwent coronary artery bypass surgery, valve surgery or combined procedures in Aalborg or Aarhus University...

  1. Alternate Fuel Cell Membranes for Energy Independence

    Energy Technology Data Exchange (ETDEWEB)

    Storey, Robson, F.; Mauritz, Kenneth, A.; Patton, Derek, L.; Savin, Daniel, A.

    2012-12-18

    The overall objective of this project was the development and evaluation of novel hydrocarbon fuel cell (FC) membranes that possess high temperature performance and long term chemical/mechanical durability in proton exchange membrane (PEM) fuel cells (FC). The major research theme was synthesis of aromatic hydrocarbon polymers of the poly(arylene ether sulfone) (PAES) type containing sulfonic acid groups tethered to the backbone via perfluorinated alkylene linkages and in some cases also directly attached to the phenylene groups along the backbone. Other research themes were the use of nitrogen-based heterocyclics instead of acid groups for proton conduction, which provides high temperature, low relative humidity membranes with high mechanical/thermal/chemical stability and pendant moieties that exhibit high proton conductivities in the absence of water, and synthesis of block copolymers consisting of a proton conducting block coupled to poly(perfluorinated propylene oxide) (PFPO) blocks. Accomplishments of the project were as follows: 1) establishment of a vertically integrated program of synthesis, characterization, and evaluation of FC membranes, 2) establishment of benchmark membrane performance data based on Nafion for comparison to experimental membrane performance, 3) development of a new perfluoroalkyl sulfonate monomer, N,N-diisopropylethylammonium 2,2-bis(p-hydroxyphenyl) pentafluoropropanesulfonate (HPPS), 4) synthesis of random and block copolymer membranes from HPPS, 5) synthesis of block copolymer membranes containing high-acid-concentration hydrophilic blocks consisting of HPPS and 3,3'-disulfonate-4,4'-dichlorodiphenylsulfone (sDCDPS), 6) development of synthetic routes to aromatic polymer backbones containing pendent 1H-1,2,3-triazole moieties, 7) development of coupling strategies to create phase-separated block copolymers between hydrophilic sulfonated prepolymers and commodity polymers such as PFPO, 8) establishment of basic

  2. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease...... as well as for cost-benefit estimation of new blood safety interventions....

  3. Liver Transplantation without Perioperative Transfusions Single-Center Experience Showing Better Early Outcome and Shorter Hospital Stay

    Directory of Open Access Journals (Sweden)

    Nicolás Goldaracena

    2013-01-01

    Full Text Available Background. Significant amounts of red blood cells (RBCs transfusions are associated with poor outcome after liver transplantation (LT. We report our series of LT without perioperative RBC (P-RBC transfusions to evaluate its influence on early and long-term outcomes following LT. Methods. A consecutive series of LT between 2006 and 2011 was analyzed. P-RBC transfusion was defined as one or more RBC units administrated during or ≤48 hours after LT. We divided the cohort in “No-Transfusion” and “Yes-Transfusion.” Preoperative status, graft quality, and intra- and postoperative variables were compared to assess P-RBC transfusion risk factors and postoperative outcome. Results. LT was performed in 127 patients (“No-Transfusion” = 39 versus “Yes-Transfusion” = 88. While median MELD was significantly higher in Yes-Transfusion (11 versus 21; P=0.0001 group, platelet count, prothrombin time, and hemoglobin were significantly lower. On multivariate analysis, the unique independent risk factor associated with P-RBC transfusions was preoperative hemoglobin (P<0.001. Incidence of postoperative bacterial infections (10 versus 27%; P=0.03, median ICU (2 versus 3 days; P=0.03, and hospital stay (7.5 versus 9 days; P=0.01 were negatively influenced by P-RBC transfusions. However, 30-day mortality (10 versus 15% and one- (86 versus 70% and 3-year (77 versus 66% survival were equivalent in both groups. Conclusions. Recipient MELD score was not a predictive factor for P-RBC transfusion. Patients requiring P-RBC transfusions had worse postoperative outcome. Therefore, maximum efforts must be focused on improving hemoglobin levels during waiting list time to prevent using P-RBC in LT recipients.

  4. [Indications and surveillance of platelet transfusions in surgery].

    Science.gov (United States)

    Coffe, C; Bardiaux, L; Couteret, Y; Devillers, M; Leroy, M; Morel, P; Pouthier-Stein, F; Hervé, P

    1995-01-01

    Surgery, after hematology, is the biggest consumer of homologous platelet concentrates. Platelet transfusion is indicated to prevent or control bleeding associated with deficiencies in platelet number or function. In surgery, general patterns (in function of pre-surgery platelet count) can be adopted in most of the indications for platelets. In emergency situations, and in some particular cases (related to the patient, the type of operation, etc.), the transfusion procedure depends on the team's experience, the results of the available clinical and biological tests, and the drugs. Strict monitoring is required during the transfusion procedure. The efficacy of the transfusion must be controlled 1 h and 24 hours after the transfusion, and a number of factors must be assessed, namely the immunological impact of the transfusion (on red blood cells, leukocytes and platelets) and the occurrence of infectious diseases transmitted via transfusion. In addition, for a possible future transfusion, a strategy must be proposed.

  5. Red cell alloimmunization and infectious marker status (human immunodeficiency virus, hepatitis B virus and hepatitis C virus in multiply transfused thalassemia patients of North India

    Directory of Open Access Journals (Sweden)

    Raj Nath Makroo

    2013-01-01

    Full Text Available Background: Patients with thalassemia major are largely transfusion dependent and are thus exposed to a variety of risks such as transmission of infectious diseases, iron overload and alloimmunization. This study was performed to determine the prevalence of human immune deficiency virus (HIV, hepatitis B virus (HBV, hepatitis C virus (HCV and red cell antibodies among multiple-transfused thalassemic patients in and around the national capital region. Materials and Methods: The Department of Transfusion Medicine, Indraprastha Apollo Hospitals, conducted this study in collaboration with the National Thalassemia Welfare Society over a period of 1 year starting February2011. Blood samples from the patients were tested for blood group, red cell alloantibody/ies, anti-HIV, anti-HCV and hepatitis B surface antigen (HBsAg by ELISA and for the respective viral ribonucleic acid (RNA or deoxyribonucleic acid (DNA by nucleic acid testing (NAT. Results: A total of 462 thalassemics which consists of 290 males and 172 females were tested. The overall alloimmunization rate was 4.1% and anti-Kell was the most common antibody identified. Thirteen cases (2.8% were positive for HBsAg by ELISA, 107 (23.1% were reactive for anti HCV and 11 (2.38% for anti HIV antibodies. Further screening and discriminatory assays by NAT confirmed the presence of HBV DNA in 11 cases, HIV RNA in 7 cases and HCV RNA in 48 cases. Conclusion: In spite of advances in Immunohematology and infectious marker testing in recent years, the rates of alloimmunization and infectious marker positivity remains high among multiply transfused patients like thalassemics. Provision of safe and adequate blood supply to these patients is a key to improving their quality-of-life and longevity.

  6. Washing of stored red blood cells by an autotransfusion device before transfusion

    NARCIS (Netherlands)

    de Vroege, R.; Wildevuur, W. R.; Muradin, J. A. G.; Graves, D.; van Oeveren, W.

    2007-01-01

    Background and Objectives The use of an autotransfusion device to wash blood of the incision site is increasing. After washing, this blood is retransfused without side effects caused by activated plasma factors and cell release products. This procedure could be extended to washing of donor blood, wh

  7. Ceramide mediates caspase-independent programmed cell death.

    Science.gov (United States)

    Thon, Lutz; Möhlig, Heike; Mathieu, Sabine; Lange, Arne; Bulanova, Elena; Winoto-Morbach, Supandi; Schütze, Stefan; Bulfone-Paus, Silvia; Adam, Dieter

    2005-12-01

    Although numerous studies have implicated the sphingolipid ceramide in the induction of cell death, a causative function of ceramide in caspase-dependent apoptosis remains a highly debated issue. Here, we show that ceramide is a key mediator of a distinct route to programmed cell death (PCD), i.e., caspase-independent PCD. Under conditions where apoptosis is either not initiated or actively inhibited, TNF induces caspase-independent PCD in L929 fibrosarcoma cells, NIH3T3 fibroblasts, human leukemic Jurkat T cells, and lung fibroblasts by increasing intracellular ceramide levels prior to the onset of cell death. Survival is significantly enhanced when ceramide accumulation is prevented, as demonstrated in fibroblasts genetically deficient for acid sphingomyelinase, in L929 cells overexpressing acid ceramidase, by pharmacological intervention, or by RNA interference. Jurkat cells deficient for receptor-interacting protein 1 (RIP1) do not accumulate ceramide and therefore are fully resistant to caspase-independent PCD whereas Jurkat cells overexpressing the mitochondrial protein Bcl-2 are partially protected, implicating RIP1 and mitochondria as components of the ceramide death pathway. Our data point to a role of caspases (but not cathepsins) in suppressing the ceramide death pathway under physiological conditions. Moreover, clonogenic survival of tumor cells is clearly reduced by induction of the ceramide death pathway, promising additional options for the development of novel tumor therapies.

  8. Blood Transfusion Strategies in Patients Undergoing Extracorporeal Membrane Oxygenation

    Directory of Open Access Journals (Sweden)

    Hyoung Soo Kim

    2017-02-01

    Full Text Available Extracorporeal membrane oxygenation (ECMO is frequently associated with bleeding and coagulopathy complications, which may lead to the need for transfusion of multiple blood products. However, blood transfusions are known to increase morbidity and mortality, as well as hospital cost, in critically ill patients. In current practice, patients on ECMO receive a transfusion, on average, of 1-5 packed red blood cells (RBCs/day, with platelet transfusion accounting for the largest portion of transfusion volume. Generally, adult patients require more transfusions than neonates or children, and patients receiving venovenous ECMO for respiratory failure tend to need smaller transfusion volumes compared to those receiving venoarterial ECMO for cardiac failure. Observation studies have reported that a higher transfusion volume was associated with increased mortality. To date, the evidence for transfusion in patients undergoing ECMO is limited; most knowledge on transfusion strategies was extrapolated from studies in critically ill patients. However, current data support a restrictive blood transfusion strategy for ECMO patients, and a low transfusion trigger seems to be safe and reasonable.

  9. Patient inclusion in transfusion medicine: current perspectives

    Directory of Open Access Journals (Sweden)

    Friedman MT

    2015-01-01

    blood transfusions via measures such as preoperative anemia management, intraoperative cell salvage, and improved transfusion guidelines. PBM strategies also focus on enhanced requirements for transfusion education and shared decision making, including informed consent and, thus, promote a patient-centered approach as defined by the Institute of Medicine. Keywords: informed consent, patient blood management, patient-centered approach, patient communication, shared decision making

  10. Importância dos carreadores de oxigênio livre de células Oxygen carriers free of cells in transfusion medicine

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Z. Novaretti

    2007-12-01

    Full Text Available Os procedimentos necessários para redução de efeitos adversos associados à transfusão de sangue, em especial aqueles decorrentes da transmissão de agentes infecciosos e da aloimunização leucócito-mediada têm impacto nos custos de produção de hemocomponentes. Paralelamente, as necessidades transfusionais têm aumentado globalmente, ficando evidente a necessidade de um substituto seguro e amplamente disponível para o sangue, chamado de sangue artificial ou de substituto do sangue. Visto que o seu desenvolvimento tem se concentrado na função de carrear oxigênio aos tecidos, daí utilizarmos, nesse texto, a denominação "Carreadores de oxigênio livre de células". Atualmente, dois tipos de carreadores de oxigênio livre de células têm sido testados: as soluções de hemoglobina modificadas (de origem humana ou bovina e os perfluorocarbonos (PFCs. Entretanto, esses produtos não são isentos de efeitos adversos e um grande número de pesquisas clínicas está em andamento para testar sua eficácia e segurança. O maior conhecimento desses carreadores de oxigênio livre de células e seus mecanismos de ação permitiu que aplicações outras, até mesmo não clínicas, estivessem em teste com as novas gerações desses produtos, expandindo assim as fronteiras da medicina transfusional.The procedures needed to reduce transfusion-associated adverse effects, especially those related to transfusion-transmitted diseases and leukocyte-mediated alloimmunization, have a great impact on the production cost of blood components. Additionally, blood transfusion has increased worldwide making the need for a safe substitute for blood evident. These products have been named artificial blood or blood substitutes. Based on the fact that their focus has been oxygen delivery to tissues, "free oxygen carrying cells" is more appropriate. Two major groups of free oxygen carring cells have been tested: modified hemoglobin solutions (bovine or human and

  11. Severe hyperkalemia following blood transfusions: Is there a link?

    Science.gov (United States)

    Rizos, Christos V; Milionis, Haralampos J; Elisaf, Moses S

    2017-01-01

    Patients with gastrointestinal bleeding often require large volume blood transfusion. Among the various side effects of blood transfusion, the increase of potassium levels is a serious one which is often overlooked. We report a case of severe hyperkalemia in a patient with gastric bleeding after large volume transfusion of packed red blood cells. The patient had hyperkalemia at baseline associated with his receiving medication as well as acute renal failure following hypovolemia. The baseline hyperkalemia was further aggravated after massive transfusions of packed red blood cells in a short period of time. The associated pathogenetic mechanisms resulting in the increase of potassium levels are presented. A number of risk factors which increase the risk of hyperkalemia after blood transfusion are discussed. Moreover, appropriate management strategies for the prevention of blood transfusion associated hyperkalemia are also presented. Physicians should always keep in mind the possibility of hyperkalemia in cases of blood transfusion. PMID:28101452

  12. One-year period prevalence of blood transfusion

    DEFF Research Database (Denmark)

    Madsen, J T; Kimper-Karl, M L; Sprogøe, U;

    2010-01-01

    Transfusion practice is reported to differ considerably between countries. Comparisons often rely on transfusion rates, incidence - or prevalence rates. In this paper, the one-year period prevalence rate (1-YPPR) of transfusion of red cells (RBC) is presented. Transfusion data, demographic data...... was 9.2/1000 citizens. Most of the transfused patients had a main diagnosis of neoplasm (22% of recipients), diseases of the circulatory system (15%), the digestive system (15%), injuries (13%) and diseases of the blood (8%). Age standardization reversed the relation between sex specific 1-YPPRs...

  13. Anemia and Blood Transfusions in Critically Ill Patients

    Directory of Open Access Journals (Sweden)

    M. Kamran Athar

    2012-01-01

    Full Text Available Anemia is common in critically ill patients. As a consequence packed red blood cell (PRBC transfusions are frequent in the critically ill. Over the past two decades a growing body of literature has emerged, linking PRBC transfusion to infections, immunosuppression, organ dysfunction, and a higher mortality rate. However, despite growing evidence that risk of PRBC transfusion outweighs its benefit, significant numbers of critically ill patients still receive PRBC transfusion during their intensive care unit (ICU stay. In this paper, we summarize the current literature concerning the impact of anemia on outcomes in critically ill patients and the potential complications of PRBC transfusions.

  14. [Allergic reactions to transfusion].

    Science.gov (United States)

    Hergon, E; Paitre, M L; Coeffic, B; Piard, N; Bidet, J M

    1987-04-01

    Frequent allergic reactions following transfusion are observed. Usually, they are benign but sometimes we observe severe allergic reactions. Adverse reactions may be brought about by least two mechanisms. First, immediate-type hypersensibility reactions due to IgE. Secondly, anaphylactic-type reactions due to interaction between transfused IgA and class specific anti IgA in the recipient's plasma. They are characterized by their severest form (anaphylactic shock). The frequency of severe reactions following the transfusion blood plasma is very low. These transfusion reactions are complement-mediated and kinins-mediated. Prevention of allergic reactions is necessary among blood donors and recipients.

  15. Predictors and patterns of red blood cell transfusion use among newly diagnosed cancer patients with chemotherapy-associated anemia in Western Denmark (1998–2003

    Directory of Open Access Journals (Sweden)

    Mellissa Yong

    2011-03-01

    Full Text Available Mellissa Yong1, Anders H. Riis3, Jon P. Fryzek2, Bjarne K. Møller4, Søren P. Johnsen3 1Department of Global Biostatistics and Epidemiology, Amgen Inc, Thousand Oaks, CA, USA; 2Department of Epidemiology and Computational Biology, Exponent, Alexandria, VA, USA; 3Department of Clinical Epidemiology; 4Department of Clinical Immunology, Aarhus University Hospital, Aarhus, DenmarkObjective: Cancer patients receiving chemotherapy are at increased risk of anemia. We conducted a population-based historical cohort study in newly diagnosed cancer patients with chemotherapy-associated anemia in order to characterize red blood cell transfusion (RBCT use.Design: This study evaluated cancer patients diagnosed between January 1, 1998 and December 31, 2003 using Danish National Patient Registry data. Patients were receiving chemotherapy and had a hemoglobin level ≤10.9 g/dL during the 4 months following cancer diagnosis. We characterized patterns of RBCT use and inpatient and outpatient hospitalization for transfusion. Adjusted Poisson regression models were used to evaluate the likelihood of RBCT, estimated by relative risk (RR, based on demographic and clinical factors.Results: Women constituted 58% of 1782 patients studied; the median age was 58 years. Two-thirds (67% had solid tumors; 67% had stage III or IV disease at diagnosis. Overall, 713 (40% patients received an RBCT within 120 days of cancer diagnosis, of which 94% were administered in the inpatient setting; 84% of these patients required subsequent transfusions. The median (Q1, Q3 pretransfusion hemoglobin level was 9.0 (8.4, 9.8 g/dL. Patients aged <20 years were more likely to receive an RBCT than older patients (RR 1.89; 95% confidence interval [CI] 1.44–2.49. Compared with stage IV disease, those with stage II or III disease had a lower likelihood of RBCT (stage II: RR 0.52, 95% CI: 0.37–0.72; stage III: RR 0.68, 95% CI: 0.55–0.83. Patients diagnosed with breast cancer were less likely

  16. A case of hyperkalemia after transfusion of irradiated red cell concentrate in mannitol-adenine-phosphate (RC-MAP)

    Energy Technology Data Exchange (ETDEWEB)

    Fukui, Akira; Yokota, Kimio; Aoki, Masanori; Sari, Atsuo [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1998-11-01

    A 72-year-old male, 45 kg in weight, underwent anterior and posterior fixations of the lumbar vertebra. Preanesthetic blood chemistry was within normal range. Following transfusion of 400 ml of RC-MAP in two hours (11 days after blood collection and 2 days after irradiation at a dose of 20 Gy), and then another 100 ml of 400 ml RC-MAP (12 days after blood collection and 2 days after irradiation at a dose of 20 Gy), the patient`s serum kalium value increased from 4.8 to 5.5 mEq/l. Even though the transfusion was immediately discontinued, the level continued to rise to 6.0 mEq/l. It subsequently fell to the normal level with glucose-insulin therapy. The hyperkalemia in this case could have been attributable to the period of storage after irradiation, the transfusion of salvaged autologous blood, and the storage state of RC-MAP. However, since the kalium values of RC-MAP and the salvaged autologous blood were not measured in this case, the exact cause was unknown. In conclusion, hyperkalemia can occur in patients during transfusion of irradiated blood. Therefore, kalium levels should be monitored carefully. (author)

  17. Addition of Sodium Pyruvate to Stored Red Blood Cells Attenuates Liver Injury in a Murine Transfusion Model

    Science.gov (United States)

    2016-01-01

    RBCs undergo numerous changes during storage and stored RBCs may induce adverse effects, ultimately resulting in organ injury in transfusion recipients. We tested the hypothesis that the addition of SP to stored RBCs would improve the quality of the stored RBCs and mitigate liver injury after transfusion in a murine model. RBCs were harvested from C57BL/6J mice and stored for 14 days in CPDA-1 containing either a solution of SP in saline or saline alone. Haemolysis, the 24-hour posttransfusion recovery, the oxygen-carrying capacity, and the SOD activity of stored RBCs were evaluated. The plasma biochemistry, hepatic MDA level, MPO activity, IL-6, TNF-α concentrations, and histopathology were measured two hours after the transfusion of stored RBCs. Compared with RBCs stored in CPDA-1 and saline, the addition of SP to stored RBCs restored their oxygen-carrying capacity and SOD activity, reduced the AST activity, BUN concentrations, and LDH activity in the plasma, and decreased the MDA level, MPO activity, and concentrations of IL-6 and TNF-α in the liver. These data indicate that the addition of SP to RBCs during storage has a beneficial effect on storage lesions in vitro and subsequently alleviates liver injury after the transfusion of stored RBCs in vivo.

  18. Net haemoglobin increase from reinfusion of refrigerated vs. frozen red blood cells after autologous blood transfusions

    DEFF Research Database (Denmark)

    Ashenden, M; Mørkeberg, Jakob Sehested

    2011-01-01

    objective was to examine which storage procedure yielded the largest increase in circulating haemoglobin after reinfusion compared to baseline. MATERIALS AND METHODS  Equal volumes of blood from 15 men were withdrawn and stored either frozen or refrigerated as packed red blood cells. Serial measures...... freezing. Nevertheless, frozen storage allowed haemoglobin to fully recover before reinfusion, while the haemoglobin was 10% lower in the refrigerated group compared with baseline. After reinfusion, the haemoglobin levels were 11·5% higher than the baseline values in the group reinfused with frozen blood......, while for the refrigerated group, haemoglobin levels were only 5·2% higher than baseline. CONCLUSION  The relatively larger recovery from anaemia in the frozen group during storage more than compensated for the larger loss of haemoglobin during freezing and resulted in a larger net gain in haemoglobin...

  19. Independent controls for neocortical neuron production and histogenetic cell death

    Science.gov (United States)

    Verney, C.; Takahashi, T.; Bhide, P. G.; Nowakowski, R. S.; Caviness, V. S. Jr

    2000-01-01

    We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm(2) was calculated and the proportionate cell death for each day of the 2-week interval was estimated. The data show that cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the 'inside-out' neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity. Copyright 2000 S. Karger AG, Basel.

  20. Smooth muscle cells largely develop independently of functional hemogenic endothelium

    Directory of Open Access Journals (Sweden)

    Monika Stefanska

    2014-01-01

    Full Text Available Vascular smooth muscle cells represent a major component of the cardiovascular system. In vitro studies have shown that FLK1+ cells derived from embryonic stem (ES cells can differentiate into both endothelial and smooth muscle cells. These FLK1+ cells also contain a mesodermal precursor, the hemangioblast, able to produce endothelial, blood and smooth muscle cells. The generation of blood precursors from the hemangioblast was recently shown to occur through a transient cell population of specialised endothelium, a hemogenic endothelium. To date, the lineage relationship between this cell population and smooth muscle cell progenitors has not been investigated. In this study, we generated a reporter ES cell line in which expression of the fluorescent protein H2B-VENUS is driven by the α-smooth muscle actin (α-SMA regulatory sequences. We demonstrated that this reporter cell line efficiently trace smooth muscle development during ES cell differentiation. Although some smooth muscle cells are associated with broad endothelial development, we established that smooth muscle cells are mostly generated independently from a specialised functional hemogenic endothelium. This study provides new and important insights into hematopoietic and vascular development, which may help in driving further progress towards the development of bioengineered vascular grafts for regenerative medicine.

  1. Platelet alloimmunization after transfusion

    DEFF Research Database (Denmark)

    Taaning, E; Simonsen, A C; Hjelms, E;

    1997-01-01

    BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patient...

  2. HIF-1α Promotes A Hypoxia-Independent Cell Migration.

    Science.gov (United States)

    Li, Liyuan; Madu, Chikezie O; Lu, Andrew; Lu, Yi

    2010-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects.

  3. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  4. [Ischemic Changes in the Electrocardiogram and Circulatory Collapse Accompanied by Severe Anemia Owing to the Delay of Red Blood Cell Concentrate Transfusion in Two Patients with Intraoperative Massive Bleeding].

    Science.gov (United States)

    Horiuchi, Toshinori; Noguchi, Teruo; Kurita, Naoko; Yamaguchi, Ayako; Takeda, Masafumi; Sha, Keiichi; Nagahata, Toshihiro

    2016-01-01

    We present two patients developing intraoperative massive bleeding and showed ischemic changes in the electrocardiogram and circulatory collapse accompanied by severe anemia owing to the delay of red blood cell concentrate transfusion. One patient underwent hepatectomy and the other pancreaticoduodenectomy. Their lowest hemoglobin concentration was around 2 g x dl(-1), and they showed ischemic changes in the electrocardiogram and severe decreases in blood pressure. The former received compatible red blood cell concentrate and the latter received uncrossmatched same blood group red blood cell concentrate immediately, and their electrocardiogram and blood pressure quickly improved. To avoid life-threatening anemia, emergency red blood cell concentrate transfusion including compatible different blood group transfusion should be applied for intraoperative massive bleeding.

  5. The Red Blood Cell Transfusion Trigger: Has the Sin of Commission Now Become a Sin of Omission?.

    Science.gov (United States)

    1997-05-01

    concentration of 10 to 12 g/dl. Human recombinant erythropoietin is also recommended for the reduction of allogeneic blood transfusions in surgical...patients. Human recombinant erythropoietin is recommended for anemic patients with hemoglobin concentrations of ■, greater than 10 g/dl and less than 13...with recombinant erythropoietin also reduces the defects in platelet adhesion and aggregation caused by uremic plasma. Thromb. Haemost. 1991;66:638

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

    Science.gov (United States)

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

    2013-08-01

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

  7. [Respiratory complications after transfusion].

    Science.gov (United States)

    Bernasinski, M; Mertes, P-M; Carlier, M; Dupont, H; Girard, M; Gette, S; Just, B; Malinovsky, J-M

    2014-05-01

    Respiratory complications of blood transfusion have several possible causes. Transfusion-Associated Circulatory Overload (TACO) is often the first mentioned. Transfusion-Related Acute Lung Injury (TRALI), better defined since the consensus conference of Toronto in 2004, is rarely mentioned. French incidence is low. Non-hemolytic febrile reactions, allergies, infections and pulmonary embolism are also reported. The objective of this work was to determine the statistical importance of the different respiratory complications of blood transfusion. This work was conducted retrospectively on transfusion accidents in six health centers in Champagne-Ardenne, reported to Hemovigilance between 2000 and 2009 and having respiratory symptoms. The analysis of data was conducted by an expert committee. Eighty-three cases of respiratory complications are found (316,864 blood products). We have counted 26 TACO, 12 TRALI (only 6 cases were identified in the original investigation of Hemovigilance), 18 non-hemolytic febrile reactions, 16 cases of allergies, 5 transfusions transmitted bacterial infections and 2 pulmonary embolisms. Six new TRALI were diagnosed previously labeled TACO for 2 of them, allergy and infection in 2 other cases and diagnosis considered unknown for the last 2. Our study found an incidence of TRALI 2 times higher than that reported previously. Interpretation of the data by a multidisciplinary committee amended 20% of diagnoses. This study shows the imperfections of our system for reporting accidents of blood transfusion when a single observer analyses the medical records.

  8. Scaffold-independent Patterning of Cells using Magnetic Nanoparticles

    Science.gov (United States)

    Ghosh, Suvojit; Biswas, Moanaro; Elankumaran, Subbiah; Puri, Ishwar

    2013-03-01

    Spatial patterning of cells in vitro relies on direct contact of cells on to solid surfaces. Scaffold independent patterning of cells has never been achieved so far. Patterning of cells has wide applications including stem cell biology, tissue architecture and regenerative medicine besides fundamental biology. Magnetized cells in a suspension can be manipulated using an externally applied magnetic field enabling directed patterning. We magnetized mammalian cells by internalization of superparamagnetic nanoparticles coated with bovine serum albumin (BSA). A magnetic field is then used to arrange cells in a desired pattern on a substrate or in suspension. The control strategy is derived from the self-assembly of magnetic colloids in a liquid considering magnetostatic interactions. The range of achievable structural features promise novel experimental methods investigating the influence of tissue shape and size on cell population dynamics wherein Fickian diffusion of autocrine growth signals are known to play a significant role. By eliminating the need for a scaffold, intercellular adhesion mechanics and the effects of temporally regulated signals can be investigated. The findings can be applied to novel tissue engineering methods.

  9. Comparison of Efficacy of Prestorage with Poststorage Leukocytoreduction Filters in Transfusion Dependent Thalassemic Patients

    Directory of Open Access Journals (Sweden)

    H. Isfahani

    2010-07-01

    Full Text Available Introduction & Objective: Cellular blood products such as whole blood, packed RBC and platelet concentrate may contain a large number of donor leukocytes. These transfused cells are responsible for several transfusion reactions which include febrile reactions, platelet refractoriness due to alloimmunization and some cell associated virus transmission, especially cytomegalovirus. Advances in biotechnology resulted in production of filters capable of depleting residual leukocytes below the threshold receded to prevent these complications. The aim of this study was to determine the efficacy of prestorage and poststorage leukocyte reduction filters.Materials & Methods: In this experimental study 140 leukocyte filters used in patients with major thalassemia with age range of 1 to 18 years old were studied. They received packed RBC with pre storage or post storage filtration in pediatric hematology clinic of Be’sat hospital, Hamadan,Iran. In addition to filter efficiency, some transfusion reactions such as hypotension, urticaria, flushing, fever and chills were analyzed with chi-square and independent t-test.Results: Calculated efficiencies of pre storage and post storage filtration were 99.70%±69% and 92.74%±12.47% respectively, which is statistically significant (P=0.000. Fever, chills, urticaria and flushing which are some transfusion reactions, were not seen in any patients received filtrated packed RBC. No transfusion complication except hypotension (which was seen in 14 patients in both groups was seen. Maximum remained leukocyte in pre storage packed RBC was 20/mm3 and 524/mm3 in post storage blood.Conclusion: According to the calculated standard deviation, pre storage leukocyte filters are superior to post storage filters, and so post storage filtration is not a reliable method to reduce remaining white blood cells in transfused blood.

  10. The Impact of Platelet Transfusion in Massively Transfused Trauma Patients

    Science.gov (United States)

    2010-11-01

    packed red blood cells [PRBC] within 24 hours of admission). Mortality was evaluated according to 4 apheresis platelet (aPLT):PRBC ratios: Low ratio (1...a massive transfusion, as the apheresis platelet-to-red cell ratio increased, a stepwise improvement in survival was seen. Prospective evaluation of...6.6 9.9 5.5 9.6 0.001 *FFP:PRBC ratio (%) (units FFP/units PRBC) 100. aPLT, apheresis platelets; FFP, fresh frozen plasma; PRBC, packed red

  11. Blood Transfusion and Donation

    Science.gov (United States)

    ... receiving the blood transfusion. To keep blood safe, blood banks carefully screen donated blood. The risk of catching ... one or more times before the surgery. A blood bank will store your blood for your use. NIH: ...

  12. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

    Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  13. Independent Stem Cell Lineages Regulate Adipose Organogenesis and Adipose Homeostasis

    Directory of Open Access Journals (Sweden)

    Yuwei Jiang

    2014-11-01

    Full Text Available Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult progenitors are specified during the developmental period and express PPARγ, they have distinct microanatomical, functional, morphogenetic, and molecular profiles. Furthermore, the two compartments derive from different lineages; whereas adult adipose progenitors fate-map from an SMA+ mural lineage, developmental progenitors do not. Remarkably, the adult progenitor compartment appears to be specified earlier than the developmental cells and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide a discrete therapeutic target for childhood and adult obesity.

  14. Age of transfused blood is not associated with increased postoperative adverse outcome after cardiac surgery.

    LENUS (Irish Health Repository)

    McKenny, M

    2011-05-01

    This study investigated the hypothesis that storage age of transfused red blood cells (RBCs) is associated with adverse outcome after cardiac surgery, and examined association between volume of RBC transfusions and outcome after cardiac surgery.

  15. Transfusion-related mortality after primary hip arthroplasty - an analysis of mechanisms and confounders

    DEFF Research Database (Denmark)

    Jans, O; Kehlet, H; Johansson, P I

    2012-01-01

    Background and Objectives Bleeding and postoperative anaemia after total hip arthroplasty (THA) may trigger transfusion of red blood cells (RBC). However, large observational studies have reported associations between RBC transfusion and increased postoperative morbidity and mortality. As major b...

  16. Blood transfusion indications in neurosurgical patients: A systematic review.

    Science.gov (United States)

    Bagwe, Shefali; Chung, Lawrance K; Lagman, Carlito; Voth, Brittany L; Barnette, Natalie E; Elhajjmoussa, Lekaa; Yang, Isaac

    2017-04-01

    Neurosurgical procedures can be complicated by significant blood losses that have the potential to decrease tissue perfusion to critical brain tissue. Red blood cell transfusion is used in a variety of capacities both inside, and outside, of the operating room to prevent untoward neurologic damage. However, evidence-based guidelines concerning thresholds and indications for transfusion in neurosurgery remain limited. Consequently, transfusion practices in neurosurgical patients are highly variable and based on institutional experiences. Recently, a paradigm shift has occurred in neurocritical intensive care units, whereby restrictive transfusion is increasingly favored over liberal transfusion but the ideal strategy remains in clinical equipoise. The authors of this study perform a systematic review of the literature with the objective of capturing the changing landscape of blood transfusion indications in neurosurgical patients.

  17. Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F;

    1989-01-01

    The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...... ranitidine, 50 mg intravenously every 6 hours for 72 hours, received perioperative blood transfusion. Eleven of these patients could be matched to 11 transfused patients not receiving perioperative ranitidine. Ranitidine prevented postoperative reduction in skin test response (+6% vs -55%, p less than 0.......0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment....

  18. Serial haematology results in transfused and non-transfused dogs naturally infected with Babesia rossi

    Directory of Open Access Journals (Sweden)

    E. Scheepers

    2011-04-01

    Full Text Available This prospective longitudinal study investigated the progression of haematological changes in 32 transfused and 54 non-transfused dogs naturally infected with Babesia rossi over the 1st 6 days following diagnosis and treatment. The effect of patient age on the results of complete blood counts was determined. Haematology data were analysed at presentation and at 24 hours, 3 days and 6 days after presentation. Dogs were treated with diminazene aceturate at diagnosis and a blood transfusion was given if deemed clinically required. Mildly to moderately regenerative normocytic normochromic anaemia was observed in all dogs throughout the study period. Transfused dogs more often had an inflammatory leukogram at presentation and at 24 hours, than dogs that were not transfused. In dogs with a left shift, a concurrent normal or decreased segmented neutrophil count was found more commonly than neutrophilia. Severe thrombocytopenia that resolved within a week was common. Blood transfusion alleviated the anaemia, but had no significant effect on white blood cell or platelet responses. Blood cell responses were not significantly influenced by age. In conclusion, the red blood cell and white blood cell responses were less than expected in dogs with babesiosis, given the degree of anaemia and inflammation present. The magnitude of thrombocytopenia and rapid return of the platelet count to normal suggested a possible immune-mediated mechanism for the thrombocytopenia.

  19. Reappraising the concept of massive transfusion in trauma

    DEFF Research Database (Denmark)

    Stanworth, Simon J; Morris, Timothy P; Gaarder, Christine;

    2010-01-01

    transfusion requirements could allow early activation of blood bank protocols. METHODS : Datasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability......ABSTRACT : INTRODUCTION : The massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens...

  20. Perioperative transfusion threshold and ambulation after hip revision surgery

    DEFF Research Database (Denmark)

    Nielsen, Kamilla; Johansson, Pär I; Dahl, Benny;

    2014-01-01

    BACKGROUND: Transfusion with red blood cells (RBC) may be needed during hip revision surgery but the appropriate haemoglobin concentration (Hb) threshold for transfusion has not been well established. We hypothesized that a higher transfusion threshold would improve ambulation after hip revision...... received RBC. CONCLUSIONS: A Hb transfusion threshold of 8.9 g/dL was associated with a statistically significantly faster TUG after hip revision surgery compared to a threshold of 7.3 g/dL but the clinical importance is questionable and the groups did not differ in Hb at the time of testing....

  1. Laryngospasm after autologous blood transfusion.

    Science.gov (United States)

    Hong, Jung; Grecu, Loreta

    2006-07-01

    Although perioperative autologous blood transfusions are associated with few side effects, transfusion reactions can occur and can be life-threatening. We report the occurrence of postoperative laryngospasm in a patient who underwent spinal anesthesia for hip surgery. The laryngospasm could not be attributed to any cause other than the autologous blood transfusion and recurred when the transfusion was restarted. Laryngospasm was successfully treated both times with positive pressure ventilation. Autologous transfusions can trigger febrile nonhemolytic transfusion reactions, which may result in airway compromise.

  2. In-flight transfusion of packed red blood cells on a combat search and rescue mission: a case report from operation enduring freedom.

    Science.gov (United States)

    West, Brad C; Bentley, Richard; Place, Ronald J

    2004-03-01

    Injuries on the battlefield can occur far from the nearest medical treatment facility. This is especially likely for downed pilots and special operations personnel. Some of these injuries lead to significant blood loss requiring transfusion. We present two cases of injured coalition force members during Operation Enduring Freedom that illustrate the potential need for a transfusion capability at the site of injury to prevent death. Consideration should be given to augmenting transfusion capabilities in military environments with predictably long evacuation times.

  3. Acquired haemophilia A as a blood transfusion emergency

    Science.gov (United States)

    Tagariello, Giuseppe; Sartori, Roberto; Radossi, Paolo; Risato, Renzo; Roveroni, Giovanni; Tassinari, Cristina; Giuffrida, Annachiara; Gandini, Giorgio; Franchini, Massimo

    2008-01-01

    Introduction Acquired haemophilia is a rare autoimmune disorder caused by autoantibodies directed in the majority of the cases against clotting factor VIII. This disorder is characterised by the sudden onset of bleeding that not rarely may be life-threatening and need transfusion support. Most reports on this condition describe the need for blood transfusions during the acute, haemorrhagic phase, but the number of transfused red cell units is often unknown. Patients and methods In the last 5 years, 14 patients with acquired haemophilia A were identified in the transfusion and haemophilia centres of Verona and Castelfranco Veneto. The transfusion support for these 14 patients was analyzed in this retrospective survey. Results The 14 patients required a total of 183 red cell units. The average transfusion requirement was 13 red cells units/patient, with a range from 0 to 38 units. Conclusions Eleven of the 14 patients studied needed strong transfusion support to enable any further management of the haemorrhages, as well as for eradication treatment of the autoantibodies to factor VIII. A relevant part of the management of haemorrhagic symptoms as well as the first choice for any further treatment (bleeding or the cure of the underlying disease) is transfusion of red blood cells. PMID:18661918

  4. The increasing importance of Intellectual Property in Transfusion Medicine.

    Science.gov (United States)

    Hardie, Ian D; Rooney, Catherine

    2011-08-01

    The Scottish National Blood Transfusion Service (SNBTS) originated in Edinburgh in the 1920's by dentist Jack Copland. Since that time the scope of Transfusion Medicine has broadened significantly to accommodate advances in technologies such as cell isolation, culture and manipulation. Many transfusion services, including SNBTS, now provide expertise both in the traditional field of blood transfusion and the newer, wider field of human cell (including 'adult' and embryonic stem cells) and tissue procurement and culture - in all the new science of "regenerative medicine". This paper describes the importance of Intellectual Property in the provision of Transfusion Medicine today and provides guidance on the management of Intellectual Property so that advances in the field have the best chance of successful translation into clinical practice.

  5. Novel web-based real-time dashboard to optimize recycling and use of red cell units at a large multi-site transfusion service

    Directory of Open Access Journals (Sweden)

    Christopher Sharpe

    2014-01-01

    Full Text Available Background: Effective blood inventory management reduces outdates of blood products. Multiple strategies have been employed to reduce the rate of red blood cell (RBC unit outdate. We designed an automated real-time web-based dashboard interfaced with our laboratory information system to effectively recycle red cell units. The objective of our approach is to decrease RBC outdate rates within our transfusion service. Methods: The dashboard was deployed in August 2011 and is accessed by a shortcut that was placed on the desktops of all blood transfusion services computers in the Capital District Health Authority region. It was designed to refresh automatically every 10 min. The dashboard provides all vital information on RBC units, and implemented a color coding scheme to indicate an RBC unit′s proximity to expiration. Results: The overall RBC unit outdate rate in the 7 months period following implementation of the dashboard (September 2011-March 2012 was 1.24% (123 units outdated/9763 units received, compared to similar periods in 2010-2011 and 2009-2010: 2.03% (188/9395 and 2.81% (261/9220, respectively. The odds ratio of a RBC unit outdate postdashboard (2011-2012 compared with 2010-2011 was 0.625 (95% confidence interval: 0.497-0.786; P < 0.0001. Conclusion: Our dashboard system is an inexpensive and novel blood inventory management system which was associated with a significant reduction in RBC unit outdate rates at our institution over a period of 7 months. This system, or components of it, could be a useful addition to existing RBC management systems at other institutions.

  6. Pathophysiology of hemolytic transfusion reactions.

    Science.gov (United States)

    Davenport, Robertson D

    2005-07-01

    Hemolytic transfusion reactions (HTR) are systemic reactions provoked by immunologic red blood cell (RBC) incompatibility. Clinical and experimental observations of such reactions indicate that they proceed through phases of humoral immune reaction, activation of phagocytes, productions of cytokine mediators, and wide-ranging cellular responses. HTR have many features in common with the systemic inflammatory response syndrome (SIRS). Knowledge of the pathophysiologic mechanisms in HTR suggest that newer biological agents that target complement intermediates or proinflammatory cytokines may be effective agents in the treatment of severe HTRs.

  7. History of blood transfusion in sub-saharan Africa.

    Science.gov (United States)

    Schneider, William H

    2013-01-01

    The adequacy and safety of blood transfusion in sub-Saharan Africa is the subject of much concern, yet there have been very few studies of its history. An overview of that record finds that transfusions were first reported in Africa (sub-Saharan and excluding South Africa) in the early 1920s, and organized transfusion practices were established before the Second World War. Blood transfusion grew rapidly after 1945, along with the construction of new hospitals and expanded health services in Africa. Significant differences existed between colonial powers in the organization of transfusion services, but these converged after independence as their use continued to grow and decentralized and hospital-based practices were adopted. It was only after the oil crisis in the mid-1970s that health spending declined and the collection, testing, and transfusion of blood began to level off. Thus, when the AIDS crisis hit transfusion services, they were already struggling to meet the needs of patients. At this time, foreign assistance as well as the World Health Organization and the League of Red Cross Societies helped respond to both the immediate problem of testing blood, and for some countries, support existed for the broader reorganization of transfusion. Overall, the history shows that transfusion was adopted widely and quickly, limited mainly by the availability of knowledgeable doctors and hospital facilities. There was less resistance than expected by Africans to receive transfusions, and the record shows a remarkable flexibility in obtaining blood. The dangers of disease transmission were recognized from an early date but were balanced against the potential lifesaving benefits of transfusion.

  8. Effect observation on red blood cell transfusion for patients with chronic aplastic anemia%基于慢性再生障碍性贫血患者的红细胞输注治疗效果观察

    Institute of Scientific and Technical Information of China (English)

    吴瑞娟

    2014-01-01

    Objective To study the clinical efficacy of red cell transfusion for patients with chronic aplastic anemia (CAA). Methods From January 2012 to December 2013 year, 98 cases of patients with chronic aplastic anemia in our hospital, the red blood cell transfusion therapy, analysis of effect of transfusion of red blood cells. Results After the treatment, patients with obvious effect, correlation infusion treatment effect and red cell preparation, and had a certain relationship with the general data of patients. 98 cases were selected, 7 cases of invalid transfusion, no efficiency was 7.1%. Conclusion Chronic aplastic anemia patients with red blood cells transfusion treatment effect will be influenced by many factors, infusion treatment process should consider all relevant factors, increase the efficacy.%目的:探讨慢性再生障碍性贫血(CAA)患者红细胞输注临床疗效。方法选取本院2012年1月~2013年12月98例慢性再生障碍性贫血患者,对其进行红细胞输注治疗,分析红细胞输注效果。结果经治疗,患者效果明显,输注治疗效果与红细胞制剂存在相关性,且与患者一般资料具有一定关系。选取的98例患者中,7例无效输注,无效率为7.1%。结论慢性再生障碍性贫血患者应用红细胞输注治疗效果会因多种因素而受到影响,输注治疗过程中需综合考虑各相关因素,增加疗效。

  9. Economics of transfusion

    NARCIS (Netherlands)

    Yeh, JM; Botteman, M; Pashos, CL; Postma, MJ; Staginnus, U

    2002-01-01

    Despite recent advances in blood screening techniques, transfusions are not risk-free procedures. Screening for viral and bacterial infections as well as other newly emerging agents continues to attract attention in the medical and health policy communities. At the same time, as healthcare costs ris

  10. Logistics of massive transfusions.

    Science.gov (United States)

    DeLoughery, Thomas G

    2010-01-01

    Care of the patient with massive bleeding involves more than aggressive surgery and infusion of large amounts of blood products. The proper management of massive transfusions-whether they are in trauma patients or other bleeding patients-requires coordination of the personnel in the surgical suite or the emergency department, the blood bank, and laboratory.

  11. Blood transfusion practices in cancer surgery

    Directory of Open Access Journals (Sweden)

    Juan P Cata

    2014-01-01

    Full Text Available Cancer patients are commonly transfused with blood products immediately before, during or after major surgery. Blood loss and haemodilution are the most common causes of red blood cells (RBCs administration and coagulopathies are the indications for the infusion of fresh-frozen plasma (FFP, cryoprecipitates and platelets. Transfusion-related immune modulation is a complication associated with the administration of blood products. A decreased immune surveillance as a consequence of blood transfusions has been linked to cancer recurrence and progression. Moreover, soluble factors present in packed RBCs, platelets and FFP can directly stimulate tumour growth and spread. Two meta-analyses suggest that the administration of blood products is associated with shorter recurrence-free survival and overall survival after colorectal cancer surgery. More studies are needed to show such association in different cancer patient populations.

  12. Interventions to reduce wrong blood in tube errors in transfusion: a systematic review.

    Science.gov (United States)

    Cottrell, Susan; Watson, Douglas; Eyre, Toby A; Brunskill, Susan J; Dorée, Carolyn; Murphy, Michael F

    2013-10-01

    This systematic review addresses the issue of wrong blood in tube (WBIT). The objective was to identify interventions that have been implemented and the effectiveness of these interventions to reduce WBIT incidence in red blood cell transfusion. Eligible articles were identified through a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, Cinahl, BNID, and the Transfusion Evidence Library to April 2013. Initial search criteria were wide including primary intervention or observational studies, case reports, expert opinion, and guidelines. There was no restriction by study type, language, or status. Publications before 1995, reviews or reports of a secondary nature, studies of sampling errors outwith transfusion, and articles involving animals were excluded. The primary outcome was a reduction in errors. Study characteristics, outcomes measured, and methodological quality were extracted by 2 authors independently. The principal method of analysis was descriptive. A total of 12,703 references were initially identified. Preliminary secondary screening by 2 reviewers reduced articles for detailed screening to 128 articles. Eleven articles were eventually identified as eligible, resulting in 9 independent studies being included in the review. The overall finding was that all the identified interventions reduced WBIT incidence. Five studies measured the effect of a single intervention, for example, changes to blood sample labeling, weekly feedback, handwritten transfusion requests, and an electronic transfusion system. Four studies reported multiple interventions including education, second check of ID at sampling, and confirmatory sampling. It was not clear which intervention was the most effective. Sustainability of the effectiveness of interventions was also unclear. Targeted interventions, either single or multiple, can lead to a reduction in WBIT; but the sustainability of effectiveness is uncertain. Data on the pre- and postimplementation of

  13. Ammonia concentration and bacterial evaluation of feline whole blood and packed red blood cell units stored for transfusion

    Directory of Open Access Journals (Sweden)

    Eva Spada

    2014-10-01

    Full Text Available Ammonia concentrations increase in human, canine and equine WB and PRBC units during storage. The aim of this study was to determine the effect of storage on ammonia concentration in feline WB and PRBC units stored in a veterinary blood bank and to evaluate possible correlations with bacterial contamination. Ammonia concentration was evaluated in 15 WB units and 2 PRBC units on day 1 and at the end of storage after 35 and 42 days, respectively. In an additional 5 WB units and 4 PRBC units ammonia concentrations were determined daily until the day the normal reference range was exceeded and then weekly to the end of storage. All units were evaluated for bacterial contamination. Ammonia increased markedly during storage as a linear function over time. On the 35th and 42th day of storage at 4±2°C mean±SD ammonia concentration reached 909±158 µg/dl and 1058±212 µg/dl in WB and PRBC units, respectively. Bacterial culture was negative in all units. High ammonia concentrations in stored WB and PRBC units could result in toxicity, particularly in feline recipients with liver failure, portosystemic shunts or those receiving large transfusion volumes. Clinical in vivo studies evaluating the effects on recipients should be performed.

  14. Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project

    Directory of Open Access Journals (Sweden)

    Bernabeu-Wittel Máximo

    2012-02-01

    Full Text Available Abstract Background Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm versus i.v. ferric carboxymaltose (FE arm versus a placebo (PLACEBO arm in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. Methods/Design Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU, or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. Discussion We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. ClinicalTrials.gov identifier: NCT01154491.

  15. Intraoperative transfusion threshold and tissue oxygenation

    DEFF Research Database (Denmark)

    Nielsen, K; Dahl, B; Johansson, P I;

    2012-01-01

    Transfusion with allogeneic red blood cells (RBCs) may be needed to maintain oxygen delivery during major surgery, but the appropriate haemoglobin (Hb) concentration threshold has not been well established. We hypothesised that a higher level of Hb would be associated with improved subcutaneous...

  16. 原发疾病对新生儿红细胞输注效果影响%Effect of the primary diseases on transfusion about the newborn red blood cells

    Institute of Scientific and Technical Information of China (English)

    曾德理; 张清; 覃碧静; 袁茜茜

    2014-01-01

    Objective:Investigating the inlfuence of diseases on transfusion about the Newborns Red blood cells to ensure blood transfusion curative effect and provide a safe and effective clinical bolld transfusion. Methods:Select red cell suspension liquid of day-age in 0-30d in a total of 152cases (excluding exchange transfusion cases and cases with hemorrhagic). Cases according to diseases are divided into sepsis group,pneumonia group, ABO hemolytic disease group and Pure neonatal anemia group. Compare the changements of Hb values according to different group with in 24h after transfusion of red cell suspension liquid. Hb values do not rise or fall ,that is, the transfusion is invalid. Result:For sepsis group,ABO hemolytic disease, pneumonia group and pure neonatal anemia group it accounted for 0.24 per cent 1.51 per cent 12.75 per cent and 22.81 per cent of the rate of rise respectively. Rates of Transfusion invalid of those groups are 54.17 per cent,46.43 per cent,25 per cent, 16.67 per cent respectively. Compare with data of those groups, the rate of rise about Hb valuse:pure neonatal anemia group肺炎组>ABO溶血病组、败血病组。红细胞输注无效率比较:单纯新生儿贫血病组﹤肺炎组﹤ABO溶血病组、败血病组,组间差异有统计学意义。结论:新生儿红细胞输注效果与所患疾病有关,各种疾病输血均有一定比例无效。因此新生儿输血应做到合理输血,注意疾病本身影响,及时检测Hb,及时调整治疗方案,以提高治疗效果。

  17. Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch.

    Science.gov (United States)

    Seidel, Hannah S; Kimble, Judith

    2015-11-09

    Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells--including germline stem cells--become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions--GLP-1/Notch signaling--becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

  18. Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine.

    Science.gov (United States)

    Wu, Yu-Wen; Goubran, Hadi; Seghatchian, Jerard; Burnouf, Thierry

    2016-04-01

    Therapeutic and diagnostic applications of nanomedicine are playing increasingly important roles in human health. Various types of synthetic nanoparticles, including liposomes, micelles, and other nanotherapeutic platforms and conjugates, are being engineered to encapsulate or carry drugs for treating diseases such as cancer, cardiovascular disorders, neurodegeneration, and inflammations. Nanocarriers are designed to increase the half-life of drugs, decrease their toxicity and, ideally, target pathological sites. Developing smart carriers with the capacity to deliver drugs specifically to the microenvironment of diseased cells with minimum systemic toxicity is the goal. Blood cells, and potentially also the liposome-like micro- and nano-vesicles they generate, may be regarded as ideally suited to perform such specific targeting with minimum immunogenic risks. Blood cell membranes are "decorated" with complex physiological receptors capable of targeting and communicating with other cells and tissues and delivering their content to the surrounding pathological microenvironment. Blood cells, such as erythrocytes, have been developed as permeable carriers to release drugs to diseased tissues or act as biofactory allowing enzymatic degradation of a pathological substrate. Interestingly, attempts are also being made to improve the targeting capacity of synthetic nanoparticles by "decorating" their surface with blood cell membrane receptor-like biochemical structures. Research is needed to further explore the benefits that blood cell-derived microvesicles, as a Trojan horse delivery systems, can bring to the arsenal of therapeutic micro- and nanotechnologies. This short review focuses on the therapeutic roles that red blood cells and platelets can play as smart drug-delivery systems, and highlights the benefits that blood transfusion expertise can bring to this exciting and novel biomedical engineering field.

  19. [Intrauterine fetal transfusion in twin pregnancy with Rh isoimmunization].

    Science.gov (United States)

    Vasileva, Iu; Poissonier, M E

    1989-01-01

    Two women with twin pregnancy and with Rhesus isoimmunization were described. The disease of these women was so grave that intrauterine transfusions were made in both fetuses (from all 86 pregnancies treated with transfusions). Twins of one of the women were born alive, but the other twins died in utero. Difficulties and problems of this rarely encountered combination of two independent one from the other pathologies are discussed.

  20. Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses.

    Science.gov (United States)

    Li, Rui; Rezk, Ayman; Li, Hulun; Gommerman, Jennifer L; Prat, Alexandre; Bar-Or, Amit

    2017-03-08

    Fungal infections (e.g., Candida albicans) can manifest as serious medical illnesses, especially in the elderly and immune-compromised hosts. T cells are important for Candida control. Whether and how B cells are involved in antifungal immunity has been less clear. Although patients with agammaglobulinemia exhibit normal antifungal immunity, increased fungal infections are reported following B cell-depleting therapy, together pointing to Ab-independent roles of B cells in controlling such infections. To test how human B cells may contribute to fungal-associated human T cell responses, we developed a novel Ag-specific human T cell/B cell in vitro coculture system and found that human B cells could induce C. albicans-associated, MHC class II-restricted responses of naive T cells. Activated B cells significantly enhanced C. albicans-mediated Th1 and Th17 T cell responses, which were both strongly induced by CD80/CD86 costimulation. IL-6(+)GM-CSF(+) B cells were the major responding B cell subpopulation to C. albicans and provided efficient costimulatory signals to the T cells. In vivo B cell depletion in humans resulted in reduced C. albicans-associated T responses. Of note, the decreased Th17, but not Th1, responses could be reversed by soluble factors from B cells prior to depletion, in an IL-6-dependent manner. Taken together, our results implicate an Ab-independent cytokine-defined B cell role in human antifungal T cell responses. These findings may be particularly relevant given the prospects of chronic B cell depletion therapy use in lymphoma and autoimmune disease, as patients age and are exposed to serial combination therapies.

  1. RED BLOOD CELL TRANSFUSION IN VERY LOW BIRTH WEIGHT INFANTS AND/OR INFANTS LESS THAN 32 WEEKS OF GESTATIONAL AGE – 4 YEARS EXPERIENCE IN A NEONATAL INTENSIVE CARE UNIT

    Directory of Open Access Journals (Sweden)

    Cátia Rodrigues Correia

    2016-06-01

    Discussion and Conclusion: RBC transfusions were more frequently used in preterm infants with lower GA and BW. Transfusion criteria applied were consistent with National Neonatal Guidelines in 2004. The transfused preterm infants had higher morbidity.

  2. Post-transfusion red cell alloimmunisation in patients with acute disorders and medical emergencies Aloimunização após transfusão de concentrado de hemácias em pacientes atendidos em um serviço de emergência

    Directory of Open Access Journals (Sweden)

    Francisco W. R. Santos

    2007-12-01

    Full Text Available Alloimmunisation following red cell transfusion is a complication in patients with chronic diseases requiring multiple transfusions. The aim of this study was to determine the frequency of alloimmunisation, to identify involved alloantibodies, to establish risk factors and to quantify the alloimmunisation risk in patients with acute disorders who received red cell transfusion at the Instituto Dr. José Frota from January 1999 to January 2001. Of the 5,690 recipients who received 16,547 units of red blood cells, 4,025 were men and 1,665 were women. Recipients with previous alloimmunisation or with time of hospital stay less than one week were excluded (n = 501. Red cell alloantibodies were detected in 120 recipients (2.1%: 60 men (1.49% and 60 women (3.60%. Alloimmunisation was 2.4 fold more frequent in women and 93.33% of the women were pregnant prevously. The average number of units transfused in the alloimmunised recipients was 4.68: 4.97 units in men and 4.40 units in women. In non-alloimmunised recipients the average was 2.87 units and the risk of alloimmunisation was 0.83%: 0.59% in men and 1.44% in women. The most frequent allo-antibodies were: anti-E (18.25% and anti-D (16.06% from a total of 137 allo-antibodies detected. The median time for detection of allo-antibodies was 20.88 days. The risk of alloimmunisation detected was high considering the average number of units transfused. The age of recipients and the longer life expectancy increase the probability of further transfusion requirements in this group. Our findings point out the necessity of modifications in the current medical transfusion support indication, including in patients with acute disorders in order to prevent alloimmunisation.A aloimunização eritrocitária após transfusão de concentrado de hemácias é uma complicação em pacientes com doenças crônicas que necessitam de transfusões de repetição. Esse estudo objetivou determinar a freqüência de aloimuniza

  3. [Effects of perioperative blood transfusion on the severity of postoperative infection].

    Science.gov (United States)

    Zhuang, Yuan; Zhang, Dong-Qing; Wang, Shu-Ying; Zhou, Wu; Pan, Ji-Chun; Wang, De-Qing

    2013-02-01

    This study was purposed to explore whether the blood transfusion of surgical patients can increase the severity of postoperative infection by a retrospective analysis of patients with postoperative infection in Chinese PLA General Hospital. By using a software "clinical transfusion database" developed by our department, 150 infected surgical cases were retrieved and divided into deep infection group and superficial infection group according to the infected location. These two groups were compared in term of the patient's age, duration of hospitalization, red blood cell transfusion volume, none-red cell transfusion volume, transfusion frequency and average transfusion volume. The results showed that red blood cell transfusion volume or none-red cells transfusion volume of patients with superficial infection was 4.50 (0 - 59) U or 2.95 (0 - 119.6) U, and that of deep infection was 9.00 (0 - 153) U and 8.05 (0 - 136.6) U, the differences was significant (P transfusion frequency showed the most significant difference, median in the patients with superficial infection was about 2 (1 - 31) times, less than the deep infection group about 4 (1 - 49) times (P transfusion volume. It is concluded that perioperative blood transfusion volume and frequency of surgical patients seems to display a positive correlation with the degree of postoperative infection.

  4. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    Science.gov (United States)

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate.

  5. Haemostatic function and biomarkers of endothelial damage before and after platelet transfusion in patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Larsen, A M; Leinøe, E B; Johansson, P I;

    2015-01-01

    OBJECTIVES: The beneficial effect of platelet transfusion on haemostasis is well established, but there is emerging evidence that platelet transfusion induces an inflammatory response in vascular endothelial cells. BACKGROUND: We investigated haemostatic function and endothelial biomarkers before...

  6. The EASTR Study: indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service.

    Science.gov (United States)

    Wells, A W; Llewelyn, C A; Casbard, A; Johnson, A J; Amin, M; Ballard, S; Buck, J; Malfroy, M; Murphy, M F; Williamson, L M

    2009-12-01

    This study provides data on National Blood Service (NBS) red blood cell (RBC, n = 9142), platelet (PLT, n = 4232) and fresh frozen plasma (FFP, n = 3584) recipients independently sampled by monthly quota from 29 representative hospitals over 12 months in 2001-2002. Hospitals were stratified by size according to total yearly RBC issues. Transfusion indications were chosen from diagnostic and procedural codes, and recipients grouped into Epidemiology and Survival of Transfusion Recipients Case-mix Groups (E-CMGs). The main E-CMGs were digestive [19% of RBC recipients; including 5% gastrointestinal (GI) bleeds and 3% colorectal surgery], musculoskeletal (15%; 12% hip and knee replacement), haematology (13%) and obstetrics and gynaecology (10%). Renal failure, fractured neck of femur, cardiac artery by-pass grafting (CABG) and paediatrics, each accounted for 3-4% recipients. FFP recipients: the main E-CMGs were digestive (21% of FFP recipients; including 7% GI bleeds and 3% colorectal surgery), hepatobiliary (15%; 7% liver disease and 2% liver transplant), cardiac (12%) and paediatrics (9%) The renal, paediatrics, vascular and haematology E-CMGs each had 6-7% of recipients. PLT recipients: the main E-CMGs were haematology (27% of PLT recipients; including 9% lymphoma and 8% acute leukaemia), cardiac (17%), paediatrics (13%), hepatobiliary (10%) and digestive (9%). Back-weighting gave national estimates of 433 000 RBC, 57 500 FFP and 41 500 PLT recipients/year in England and North Wales, median age 69, 64 and 59 years, respectively. Digestive and hepatobiliary indications emerged as the top reason for transfusion in RBC and FFP recipients, and was also a frequent indication in PLT recipients.

  7. Scientific and forensic standards for homologous blood transfusion anti-doping analyses.

    Science.gov (United States)

    Giraud, Sylvain; Robinson, Neil; Mangin, Patrice; Saugy, Martial

    2008-07-18

    Since the introduction in 2001 of a urine-based detection method for recombinant erythropoietin (rHuEPO), transfusion-doping practices have regained interest. To address this problem, an efficient antidoping test designed to obtain direct proof of allogeneic blood transfusion was developed and validated. This test, based on flow cytometry analysis of red blood cell (RBCs) phenotypes, was used to determine the absence or the presence of numerous RBCs populations in a blood sample. A such, it may constitute a direct proof of an abnormal blood population resulting from homologous transfusion. Single-blind and single-site studies were carried out to validate this method as a forensic quality standard analysis and to allow objective interpretation of real cases. The analysis of 140 blood samples containing different percentages (0-5%) of a minor RBCs population were carried on by four independent analysts. Robustness, sensitivity, specificity, precision and stability were assessed. ISO-accredited controls samples were used to demonstrate that the method was robust, stable and precise. No false positive results were observed, resulting in a 100% specificity of the method. Most samples containing a 1.5% minor RBCs population were unambiguously detected, yielding a 78.1% sensitivity. These samples mimicked blood collected from an athlete 3 months after a homologous blood transfusion event where 10% of the total RBCs present in the recipient originated in the donor. The observed false negative results could be explained by differences in antigen expression between the donor and the recipient. False negatives were more numerous with smaller minor RBCs populations. The method described here fulfils the ISO-17025 accreditation and validation requirements. The controls and the methodology are solid enough to determine with certainty whether a sample contains one or more RBCs populations. This variable is currently the best indicator for homologous blood transfusion doping.

  8. Qualitative research in transfusion medicine.

    Science.gov (United States)

    Arnold, E; Lane, S

    2011-10-01

    Transfusion medicine research has traditionally employed quantitative methods to answer clinical research questions. Increasingly, qualitative research methods are being used in the field to address a wide variety of research questions in areas such as blood donation, transfusion practices and policy development. This article describes the key characteristics, methodologies and methods of qualitative research and draws on examples to show how qualitative research approaches have been applied in the field of transfusion medicine. It is hoped that this overview will inform and encourage the application of qualitative research in the field of transfusion medicine.

  9. 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)

  10. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

    Directory of Open Access Journals (Sweden)

    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  11. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.

    Science.gov (United States)

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins.

  12. Timing and Location of Blood Product Transfusion and Outcomes in Massively Transfused Combat Casualties

    Science.gov (United States)

    2012-01-01

    blood components in a 1:1:1 ratio of platelets:fresh frozen plasma:red blood cells (RBCs) is based on analyses of massive transfusion (MT, Q10 RBC units in 24 hours). These 24-hour analyses are weakened by survival bias and do not describe the timing and location of transfusions. Mortality outcomes associated with early (first 6 hours) resuscitation incorporating platelets, for combat casualties requiring MT, have not been reported. METHODS: We analyzed records for 8,618 casualties treated at the United States military hospital in Baghdad, Iraq, between January 2004 and

  13. Blood transfusion exposure in Denmark and Sweden

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Edgren, Gustaf; Rostgaard, Klaus

    2009-01-01

    Although essential for the evaluation of blood transfusion safety, the prevalence of blood transfusion in the general population is not presently known. This study estimated the exposure to blood transfusion in the general Scandinavian population....

  14. Circadian-independent cell mitosis in immortalized fibroblasts.

    Science.gov (United States)

    Yeom, Mijung; Pendergast, Julie S; Ohmiya, Yoshihiro; Yamazaki, Shin

    2010-05-25

    Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperature-compensated such that the period of the rhythm remains constant (approximately 24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is temperature-compensated. Twenty-four-hour fluctuations in cell division have also been observed in numerous species, suggesting that the circadian system is regulating the timing of cell division. We tested whether the cell-cycle rhythm was coupled to the circadian system in immortalized rat-1 fibroblasts by monitoring cell-cycle gene promoter-driven luciferase activity. We found that there was no consistent phase relationship between the circadian and cell cycles, and that the cell-cycle rhythm was not temperature-compensated in rat-1 fibroblasts. These data suggest that the circadian system does not regulate the cell-mitosis rhythm in rat-1 fibroblasts. These findings are inconsistent with numerous studies that suggest that cell mitosis is regulated by the circadian system in mammalian tissues in vivo. To account for this discrepancy, we propose two possibilities: (i) There is no direct coupling between the circadian rhythm and cell cycle but the timing of cell mitosis is synchronized with the rhythmic host environment, or (ii) coupling between the circadian rhythm and cell cycle exists in normal cells but it is disconnected in immortalized cells.

  15. TRANSFUSION REQUIREMENT AND COMPLICATION IN CHILDREN ADMITTED IN A TERTIARY HOSPITAL

    Directory of Open Access Journals (Sweden)

    Booma

    2016-05-01

    Full Text Available BACKGROUND Indications for transfusion include symptomatic anaemia, haemolytic anaemia, haematological malignancy, acute sickle cell crisis, and acute blood loss of more than 30 percent of blood volume, sepsis, etc. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Platelet transfusion is indicated to prevent haemorrhage in patients with thrombocytopenia or platelet function defects. Cryoprecipitate is used in cases of hyperfibrinogenaemia, which most often occurs in the setting of massive haemorrhage or consumptive coagulopathy, factor VIII deficiency and Von Willebrand disease as an alternate to specific component therapy. Transfusion-related infections are less common than non-infectious complications. All non-infectious complications of transfusion are classified as non-infectious serious hazards of transfusion. Acute complications occur within minutes to 24 hours of the transfusion, whereas delayed complications may develop days, months or even years later. Blood transfusion can be a lifesaving procedure, but it has risks, including infectious and non-infectious complications. There is debate in the medical literature concerning the appropriate use of blood and blood products. Clinical trials investigating their use suggest that waiting to transfuse at lower haemoglobin levels is beneficial. This study will consider the indications for transfusion of blood and blood products, and will discuss common non-infectious complications associated with transfusion. Requirement of blood and blood component transfusions in children admitted in a tertiary care hospital and its related complications. OBJECTIVE To evaluate the pattern of transfusion requirement in children admitted in a tertiary care hospital and the frequency of transfusion related complications. METHODS Children of various age groups presenting with clinical profile like symptomatic anaemia, haemolytic anaemia, haematological malignancy, acute sickle cell

  16. Circadian-independent cell mitosis in immortalized fibroblasts

    OpenAIRE

    Yeom, Mijung; Pendergast, Julie S.; Ohmiya, Yoshihiro; Yamazaki, Shin

    2010-01-01

    Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperature-compensated such that the period of the rhythm remains constant (~24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is ...

  17. Monitoring compliance with transfusion guidelines in hospital departments by electronic data capture

    DEFF Research Database (Denmark)

    Norgaard, Astrid; De Lichtenberg, Trine Honnens; Nielsen, Jens

    2014-01-01

    and per hospital admission. Transfusion practice was more liberal in surgical and intensive care units than in medical departments. DISCUSSION: We described pre-transfusion haemoglobin levels, transfusion rates and volumes at hospital and departmental levels, and in surgical subpopulations. Initial data...... volumes. RESULTS: The model dataset include 33,587 admissions, of which 10% had received at least one unit of red blood cells. Haemoglobin measurements preceded 96.7% of the units transfused. The median pre-transfusion haemoglobin was 8.9 g/dL (interquartile range 8.2-9.7) at the hospital level. In only 6......-transfusion haemoglobin levels at the departmental level. In a tertiary care hospital, no such data were produced before this study. Our aim was to establish a Patient Blood Management database based on electronic data capture in order to monitor compliance with transfusion guidelines at departmental and hospital levels...

  18. Contact-independent cell death of human microglial cells due to pathogenic Naegleria fowleri trophozoites.

    Science.gov (United States)

    Kim, Jong-Hyun; Kim, Daesik; Shin, Ho-Joon

    2008-12-01

    Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

  19. Prevention and management of transfusion-induced alloimmunization: current perspectives

    Directory of Open Access Journals (Sweden)

    Hauck-Dlimi B

    2014-08-01

    Full Text Available Barbara Hauck-Dlimi, Susanne Achenbach, Julian Strobel, Reinhold Eckstein, Robert Zimmermann Department of Transfusion Medicine and Haemostaseology, University Hospital Erlangen, Erlangen, Germany Abstract: Transfusion of blood components, transplantations, and exchange of blood between mother and child during pregnancy or at birth can lead to alloimmunization. Because of its clinical relevance, this review brings into focus alloimmunization against red blood cells, human platelet antigens, human leukocyte antigens, and human neutrophil antigens. In principle, an individual is able to develop antibodies after exposure to a nonautogenous antigen, but these cells actually induce alloimmunization only for a minority of patients. An individual producing alloantibodies after having contact with foreign antigens depends on various factors, such as genetic predisposition, underlying diseases, the patient's immune status, and clinical immune modulation. When alloimmunization has occurred, it could lead to problems for future transfusions or transplantations. Keywords: transfusion, alloimmunization, prevention

  20. Transfusion service disaster planning.

    Science.gov (United States)

    Bundy, K L; Foss, M L; Stubbs, J R

    2008-01-01

    The Mayo Clinic, in Rochester, Minnesota, recently set forth a directive to develop a Mayo Emergency Incident Command System (MEICS) plan to respond to major disasters. The MEICS plan that was developed interfaces with national response plans to ensure effective communication and coordination between our institution and local, state, and federal agencies to establish a common language and communication structure. The MEICS plan addresses multiple aspects of dealing with resource needs during a crisis, including the need for blood and transfusion medicine services. The MEICS plan was developed to supplement our current local emergency preparedness procedures and provide a mechanism for responding to the escalating severity of an emergency to deal with situations of a magnitude that is outside the normal experience. A plan was developed to interface the existing Transfusion Medicine disaster plan standard operating procedures (SOP) with the institutional and Department of Laboratory Medicine (DLMP) MEICS plans. The first step in developing this interface was defining MEICS. Other major steps were defining the chain of command, developing a method for visually indicating who is "in charge," planning communication, defining the actions to be taken, assessing resource needs, developing flowcharts and updating SOPs, and developing a blood rationing team to deal with anticipated blood shortages. Several key features of the interface and updated disaster plan that were developed are calling trees for response personnel, plans for relocating leadership to alternative command centers, and action sheets to assist with resource assessment. The action sheets also provide documentation of key actions by response personnel.

  1. Detrimental effects of perioperative blood transfusion

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1995-01-01

    Evidence suggests that perioperative allogeneic blood transfusion increases the risk of infectious complications after major surgery and of cancer recurrence after curative operation. This has been attributed to immunosuppression. Several authors have suggested that filtered whole blood and/or red...... similar postoperative infectious complications and cancer recurrence and/or survival rates in patients receiving autologous blood donated before operation and those receiving allogeneic blood. Future studies should identify common risk factors associated with blood storage....... cell concentrate, or leucocyte- and buffy coat-reduced red cells in artificial medium or their own plasma, may reduce postoperative immunosuppression. It was also anticipated that the use of autologous blood might minimize the risk of perioperative transfusion, but studies have unexpectedly shown...

  2. Detrimental effects of perioperative blood transfusion

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1995-01-01

    Evidence suggests that perioperative allogeneic blood transfusion increases the risk of infectious complications after major surgery and of cancer recurrence after curative operation. This has been attributed to immunosuppression. Several authors have suggested that filtered whole blood and/or red...... cell concentrate, or leucocyte- and buffy coat-reduced red cells in artificial medium or their own plasma, may reduce postoperative immunosuppression. It was also anticipated that the use of autologous blood might minimize the risk of perioperative transfusion, but studies have unexpectedly shown...... similar postoperative infectious complications and cancer recurrence and/or survival rates in patients receiving autologous blood donated before operation and those receiving allogeneic blood. Future studies should identify common risk factors associated with blood storage....

  3. Transfusion in critically ill children

    DEFF Research Database (Denmark)

    Secher, E L; Stensballe, J; Afshari, A

    2013-01-01

    Transfusion of blood products is a cornerstone in managing many critically ill children. Major improvements in blood product safety have not diminished the need for caution in transfusion practice. In this review, we aim to discuss the interplay between benefits and potential adverse effects...... of transfusion in critically ill children by including 65 papers, which were evaluated based on previously agreed selection criteria. Current practice on transfusing critically ill children is mainly founded on the basis of adult studies, common practices with cut-off values, and expert opinions, rather than...... evidence-based medicine. Paediatric patients have explicit physiological challenges and requirements to be addressed. Critically ill children often suffer from anaemia, have substantial iatrogenic blood loss with subsequent transfusions, and are at a higher risk of complications, often due to human errors...

  4. Fatores preditivos da transfusão de concentrado de hemácias em pacientes submetidos a cirurgias eletivas do aparelho digestivo: uma análise interinstitucional Predictive factors associated with packed red cell transfusions in patients submitted to elective surgery of the digestive tract: an inter-institutional analysis

    Directory of Open Access Journals (Sweden)

    Antonio Sergio Barcala Jorge

    2010-01-01

    Full Text Available O objetivo desse estudo foi compreender os fatores determinantes da prática transfusional de concentrado de hemácias em cirurgias eletivas do aparelho digestivo em quatro unidades hospitalares em Montes Claros, Minas Gerais, Brasil. Foi realizado um estudo descritivo, analítico e retrospectivo através do levantamento de dados em prontuários clínicos de quatro unidades hospitalares de onde foram catalogados os dados de pacientes a partir de junho de 2007 a dezembro de 2008, referentes às cirurgias citadas. Os resultados evidenciaram 81 casos, sendo 42% do gênero feminino e 58% do masculino. A idade média foi de 55,5 anos (±19,11 anos. As enfermidades de base reportadas mais comuns foram os processos neoplásicos (42%. Desses 81 pacientes, 38 (47% foram hemotransfundidos no pré-operatório imediato, 28 (18% foram transfundidos no transcirúrgico e 37 (45,7% no pós-operatório imediato. Na análise univariada houve diferenças entre a prática transfusional pré-cirúrgica interinstitucional. Na fase cirúrgica houve relação entre a prática transfusional com a citação de motivos, fator RH (Rhesus, prática institucional e doença de base. Na fase pós-cirúrgica não foram demonstradas relações. Em todas as fases, não houve associação da prática transfusional com os tipos de procedimentos cirúrgicos, com o índice ASA (American Society of Anesthesiology e valores de hemoglobina e hematócrito. Concluindo, esse estudo revelou que a prática transfusional foi heterogênea entre instituições hospitalares, careceu de valores laboratoriais específicos, relacionou-se com a patologia de base mas não com o tipo de procedimento cirúrgico e foi norteada pelo critério de escolha do profissional.The objective of this study was to understand the determinative factors for packed red cell transfusions in elective digestive tract surgeries in four hospital units in Montes Claros, Minas Gerais, Brazil. Retrospective analyses were

  5. Randomised comparison of leucocyte-depleted versus buffy-coat-poor blood transfusion and complications after colorectal surgery

    DEFF Research Database (Denmark)

    Jensen, L S; Kissmeyer-Nielsen, P; Wolff, B;

    1996-01-01

    surgery were randomised to receive buffy-coat poor (n = 299) or filtered leucocyte-depleted red-cells (n = 290) when transfusion was indicated. 260 patients actually received blood transfusion. Three patients were excluded from analysis. FINDINGS: The 142 patients randomised to and transfused with buffy...

  6. Dendritic planarity of Purkinje cells is independent of Reelin signaling.

    Science.gov (United States)

    Kim, Jinkyung; Park, Tae-Ju; Kwon, Namseop; Lee, Dongmyeong; Kim, Seunghwan; Kohmura, Yoshiki; Ishikawa, Tetsuya; Kim, Kyong-Tai; Curran, Tom; Je, Jung Ho

    2015-07-01

    The dendritic planarity of Purkinje cells is critical for cerebellar circuit formation. In the absence of Crk and CrkL, the Reelin pathway does not function resulting in partial Purkinje cell migration and defective dendritogenesis. However, the relationships among Purkinje cell migration, dendritic development and Reelin signaling have not been clearly delineated. Here, we use synchrotron X-ray microscopy to obtain 3-D images of Golgi-stained Purkinje cell dendrites. Purkinje cells that failed to migrate completely exhibited conical dendrites with abnormal 3-D arborization and reduced dendritic complexity. Furthermore, their spines were fewer in number with a distorted morphology. In contrast, Purkinje cells that migrated successfully displayed planar dendritic and spine morphologies similar to normal cells, despite reduced dendritic complexity. These results indicate that, during cerebellar formation, Purkinje cells migrate into an environment that supports development of dendritic planarity and spine formation. While Reelin signaling is important for the migration process, it does not make a direct major contribution to dendrite formation.

  7. Cell volume and membrane stretch independently control K+ channel activity

    DEFF Research Database (Denmark)

    Bomholtz, Sofia Hammami; Willumsen, Niels J; Olsen, Hervør L;

    2009-01-01

    A number of potassium channels including members of the KCNQ family and the Ca(2+) activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch....... To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current...... was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not mimicked by membrane stress induced by cell swelling, and (2) activation of KCNQ1 channels by cell volume increase is not mediated by local tension in the cell membrane. We conclude...

  8. Curcumin induces apoptosis-independent death in oesophageal cancer cells.

    LENUS (Irish Health Repository)

    O'Sullivan-Coyne, G

    2009-10-06

    Background:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.Results:Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.British Journal of Cancer advance online publication, 6 October 2009; doi:10.1038\\/sj.bjc.6605308 www.bjcancer.com.

  9. Curcumin induces apoptosis-independent death in oesophageal cancer cells.

    LENUS (Irish Health Repository)

    O'Sullivan-Coyne, G

    2012-01-31

    BACKGROUND: Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines. METHODS: MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting. RESULTS: Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug. CONCLUSION: Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.

  10. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

    Science.gov (United States)

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-09

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

  11. Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F;

    1989-01-01

    The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...... delayed-type antigens in 83 consecutive patients undergoing major elective abdominal surgery. Sixty-six of these patients were randomly divided into ranitidine or no-ranitidine-treatment groups, and the remaining 17 patients were operated on without ranitidine. Thus, 50 patients were operated on without.......0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment....

  12. Reappraising the concept of massive transfusion in trauma

    DEFF Research Database (Denmark)

    Stanworth, Simon J; Morris, Timothy P; Gaarder, Christine;

    2010-01-01

    ABSTRACT : INTRODUCTION : The massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens...... of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive...... : No threshold for definition exists at which a massive transfusion specifically results in worse outcomes. Even with a large sample size across multiple trauma datasets, it was not possible to develop a transportable and clinically useful prediction model based on available admission parameters. Massive...

  13. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn;

    2014-01-01

    BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care...... unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay...... were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion...

  14. Transfusion regimens in thalassemia intermedia

    Directory of Open Access Journals (Sweden)

    Z. Karakas

    2011-12-01

    Full Text Available Thalassemia intermedia (TI is a heterogeneous disease, in terms of both clinical manifestations and underlying molecular defects. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from early childhood. In contrast with patients with Thalassemia major (TM, the severity of anemia is less and the patients do not require transfusions during at least the first few years of life. Many patients with TI, especially older ones, have been exposed to the multiple long-term effects of chronic anemia and tissue hypoxia and their compensatory reactions, including enhanced erythropoiesis and increased iron absorption. Bone marrow expansion and extramedullary hematopoiesis lead to bone deformities and liver and spleen enlargement. Therapeutic strategies in TI are not clear and different criteria are used to decide the initiation of transfusion and chelation therapy, modulation of fetal hemoglobin production, and hematopoietic stem cell transplantation on an individual basis. The clinical picture of well-treated TM patients with regular transfusionchelation therapy is better from TI patients who have not received adequate transfusion therapy. There is a significant role of early blood transfusion to prevent and treat complications commonly associated with TI, such as extramedullary erythropoiesis and bone deformities, autoimmune hemolytic anemia, leg ulcers, gallstones, pseudoxantoma elasticum, hyperuricosuria, gout and pulmonary hypertension, which are rarely seen in thalassemia major. Nowadays, indications of transfusion in patients with TI are chronic anemia (Hb < 7 g/dL, bone deformities, growth failure, extramedullary erythropoiesis, heart failure, pregnancy and preparation for surgical procedures. Conclusion: Adequate (regular or tailored transfusion therapy is an important treatment modality for increasing the quality of life in patients with thalassemia intermedia during childhood. 就临床表象和潜在的分子缺

  15. PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Sophia Boyoung Lee

    Full Text Available PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.

  16. Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction.

    Science.gov (United States)

    Tezuka, Hiroyuki; Abe, Yukiko; Asano, Jumpei; Sato, Taku; Liu, Jiajia; Iwata, Makoto; Ohteki, Toshiaki

    2011-02-25

    Although both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) are present in the gut-associated lymphoid tissues (GALT), the roles of pDCs in the gut remain largely unknown. Here we show a critical role for pDCs in T cell-independent (TI) IgA production by B cells in the GALT. When pDCs of the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) (which are representative GALT) were cultured with naive B cells to induce TI IgA class switch recombination (CSR), IgA production was substantially higher than in cocultures of these cells with cDCs. IgA production was dependent on APRIL and BAFF production by pDCs. Importantly, pDC expression of APRIL and BAFF was dependent on stromal cell-derived type I IFN signaling under steady-state conditions. Our findings provide insight into the molecular basis of pDC conditioning to induce mucosal TI IgA production, which may lead to improvements in vaccination strategies and treatment for mucosal-related disorders.

  17. Transfusion-transmitted Chagas' disease.

    Science.gov (United States)

    Wendel, S

    1998-11-01

    Transfusion-transmitted Chagas' disease has been recognized since 1952. Until recently, no cases were reported outside of Latin America. However, emigration during the past 20 years expanded its transfusional geographic borders to North America. Trypanosoma cruzi-infected donors usually are asymptomatic, often for a lifetime. This situation complicates donor screening, particularly in regions where blood bank personnel are not familiar with the risk factors and natural history of this transfusion-transmitted infection. This review addresses the main aspects of epidemiology, risks of infection, clinical symptoms in donors and recipients, preventive measures, and blood donor screening to prevent transfusion-transmitted Chagas' disease.

  18. Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry.

    Science.gov (United States)

    Shimojima, Masayuki; Ströher, Ute; Ebihara, Hideki; Feldmann, Heinz; Kawaoka, Yoshihiro

    2012-02-01

    Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa virus receptors advances our understanding of Lassa virus cell entry.

  19. Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Jing Liu; Yi Gao; Shuan Wang; Er-Wei Sun; Yu Wang; Zhi Zhang; Yi-Qiang Shan; Shi-Zheng Zhong

    2005-01-01

    AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation.METHODS: Two of Wistar rats were chosen randomly for normal liver pathology control and ten of SD rats chosen randomly for liver function control as blank group (no operation). The rest of Wistar and SD rats were divided into four groups: control group (only liver transplantation),Dex group (donors receiving intraperitoneal injection of dexamethasone), SpC group (recipients receiving infusion of spleen cells of donors), Dex-SpC group (recipients receiving infusion of apoptotic spleen cells of donors),with each group except blank group, containing 10 SD rats and 10 Wistar rats, respectively. Wistar rats received liver transplantation from SD rats, in the meantime they received infusion of spleen cells of donors, which were induced by an intraperitoneal injection of dexamethasone The serum alanine transaminase (ALT), total bilirubin (T bili), liver pathological changes and survival time were analysed. Statistical analysis was carried out using SPSS 10.0 for Windows. Differences of the parametric data of ALT in means were examined by one-way ANOVA.Differences of ALT between two groups were examined by LSD. Differences of the nonparametric data of T bili in means and scores of pathology classification for acute rejection were examined by Kruskal-Willis H test. The correlations between ALT and T bili were analysed by Bivariate. Kaplan-Meier curves were used to demonstrate survival distribution. The log-rank test was used to compare the survival data.RESULTS: There were significant differences in ALT of the five groups (F= 23.164 P= 0.000), and ALT in DexSpC group was significantly higher than that in blank control, control, Dex, and SpC groups (P = 0.000), and ALT in SpC group was significantly higher than that in blank control (P = 0.000), control (P = 0.004), and Dex groups (P = 0.02). Results of

  20. Clinical assessment of quality of life of the patients with chronic blood transfusion and chelation therapy

    Directory of Open Access Journals (Sweden)

    Tamil Selvan

    2014-01-01

    Full Text Available Background: The patient with hemoglobinopathy like thalassemia major (TM, bone marrow dysfunction, and sickle cell disease are requiring chronic blood transfusion for their life time to survive. Among these, TM is one of the most common hemoglobinopathy worldwide. Objective: This study is done to assess the quality of life (QOL of the patients with chronic blood transfusion and chelation therapy. Materials and Methods: The QOL scores were obtained through the self-administered SF-36 questionnaire. The study subjects were asked to answer the SF-36 questionnaire once every 3 months. Results: After 6 months, the SF 36 general health mean score was 63.58 ± 12.98 (P < 0.05. The highest mean score was 69.37 ± 11.61. The mean difference after the final reviews was statistically significant. Conclusion: The preponderance of scores used to assess QOL suggests that there is a direct and independent effect on QOL when treated with transfusion and iron-chelation therapy.

  1. 儿童造血干细胞移植过程中影响血小板输注效果部分因素探讨%Influencing Factors of Platelet Transfusion during Stem Cell Transplantation of Children

    Institute of Scientific and Technical Information of China (English)

    张传仓; 胡波; 司英健; 吴涛

    2011-01-01

    Objective To observe the influencing factors of platelet transfusion during stem cell transplantation of children. Methods Three hundred and five times of platelet transfusions of patients in blank periods of bone marrow after stem cell transplantation were retrospectively analyzed. The relationship between the incidences of refractoriness of platelet transfusion (RPT) and the genders, platelet inventorial times, original diseases, types of transplantation, the adjusted corrected count increment (aCCI) and were compared respectively. Results Female and auto-HSCT had more effective platelet transfusion,whereas severe aplastic anemia and myelodysplastic syndrome had worse platelet transfusion; no significant meanings were found between the aCCI and the incidence of RPT in platelet inventorial times.Conclusion The genders, original diseases and types of transplantation were important factors in platelet transfusion. The platelet inventorial time had little effect on platelet transfusion.%目的 初步探讨儿童造血干细胞移植过程中影响血小板输注效果的因素.方法 回顾性分析了处于骨髓清空期的造血干细胞移植患儿的305次血小板输注情况,观察患儿性别、所患疾病、移植类型及血小板库存天数与调整后的血小板计数增加值校正指数(aCCI)和血小板无效输注的发生率之间的关系.结果 女性患儿血小板输注效果优于男性(F=2.101,P=0.037),无效输注发生率明显低于男性(χ2=5.968,P=0.015);有效期内的血小板库存天数对aCCI值及无效输注发生率没有显著影响(P=0.346及0.086);急性再生障碍性贫血及骨髓增生异常综合征患儿更易发生无效输注,而自体造血干细胞移植较少发生无效输注.结论 患儿性别、所患疾病及移植类型的不同是影响血小板输注效果的重要原因,而有效期内的库存天数,对血小板的输注效果没有显著影响.

  2. Double precision nonlinear cell for fast independent component analysis algorithm

    Science.gov (United States)

    Jain, V. K.

    2006-05-01

    Several advanced algorithms in defense and security objectives require high-speed computation of nonlinear functions. These include detection, localization, and identification. Increasingly, such computations must be performed in double precision accuracy in real time. In this paper, we develop a significance-based interpolative approach to such evaluations for double precision arguments. It is shown that our approach requires only one major multiplication, which leads to a unified and fast, two-cycle, VLSI architecture for mantissa computations. In contrast, the traditional iterative computations require several cycles to converge and typically these computations vary a lot from one function to another. Moreover, when the evaluation pertains to a compound or concatenated function, the overall time required becomes the sum of the times required by the individual operations. For our approach, the time required remains two cycles even for such compound or concatenated functions. Very importantly, the paper develops a key formula for predicting and bounding the worst case arithmetic error. This new result enables the designer to quickly select the architectural parameters without the expensive and intolerably long simulations, while guaranteeing the desired accuracy. The specific application focus is the mapping of the Independent Component Analysis (ICA) technique to a coarse-grain parallel-processing architecture.

  3. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  4. Transfusion in transplant patients: the good, the bad, and the ugly.

    Science.gov (United States)

    Klein, H G

    1993-01-01

    Several transfusion-related complications have particular relevance to the transplant setting. Transfusions reportedly improve solid organ graft survival, especially when the donor and recipient share at least one HLA-DR antigen. Whereas the mechanism for this effect is unclear, less favorable "immunomodulating" effects of transfusion may increase postoperative infections and shorten survival time and disease-free intervals in patients with a variety of malignancies who are undergoing surgery. The contribution of the different components of the blood transfusion to these outcomes remains speculative. Directed donations, especially from relatives and in the setting of a recipient who is immunosuppressed, may give rise to a severe but under-appreciated immunologic consequence of transfusion: graft-versus-host disease. Although still rarely reported, transfusional graft-versus-host disease is almost invariably fatal. This complication is entirely avoidable if the transfused blood product is appropriately gamma-irradiated. Infectious complications remain the most feared consequence of transfusion; the cytomegalovirus, the human immunodeficiency virus, and hepatitis B and C may run a more fulminant course in transplant patients who are immunosuppressed. Red cell substitutes, hematopoietic growth factors, and autologous transfusion are among the strategies for preventing complications of blood transfusion. With the advent of cyclosporine and more potent and specific immunosuppressive therapies, the desirability of preoperative transfusion for organ grafts warrants reevaluation.

  5. Perioperative blood transfusion does not decrease survival after surgical treatment of spinal metastases

    DEFF Research Database (Denmark)

    Clausen, Caroline; Lönn, Lars; Morgen, Søren Schmidt;

    2014-01-01

    PURPOSE: To assess whether perioperative allogenic blood transfusions in patients undergoing surgical treatment for spinal metastases independently influence patient survival. METHODS: A retrospective study including 170 consecutive patients undergoing surgical treatment for spinal metastases...

  6. Benchmarking: applications to transfusion medicine.

    Science.gov (United States)

    Apelseth, Torunn Oveland; Molnar, Laura; Arnold, Emmy; Heddle, Nancy M

    2012-10-01

    Benchmarking is as a structured continuous collaborative process in which comparisons for selected indicators are used to identify factors that, when implemented, will improve transfusion practices. This study aimed to identify transfusion medicine studies reporting on benchmarking, summarize the benchmarking approaches used, and identify important considerations to move the concept of benchmarking forward in the field of transfusion medicine. A systematic review of published literature was performed to identify transfusion medicine-related studies that compared at least 2 separate institutions or regions with the intention of benchmarking focusing on 4 areas: blood utilization, safety, operational aspects, and blood donation. Forty-five studies were included: blood utilization (n = 35), safety (n = 5), operational aspects of transfusion medicine (n = 5), and blood donation (n = 0). Based on predefined criteria, 7 publications were classified as benchmarking, 2 as trending, and 36 as single-event studies. Three models of benchmarking are described: (1) a regional benchmarking program that collects and links relevant data from existing electronic sources, (2) a sentinel site model where data from a limited number of sites are collected, and (3) an institutional-initiated model where a site identifies indicators of interest and approaches other institutions. Benchmarking approaches are needed in the field of transfusion medicine. Major challenges include defining best practices and developing cost-effective methods of data collection. For those interested in initiating a benchmarking program, the sentinel site model may be most effective and sustainable as a starting point, although the regional model would be the ideal goal.

  7. Autoimmune hemolytic anemia: transfusion challenges and solutions

    Directory of Open Access Journals (Sweden)

    Barros MM

    2017-03-01

    Full Text Available Melca M O Barros, Dante M Langhi Jr, José O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA is defined as the increased destruction of red blood cells (RBCs in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct ­antiglobulin test

  8. Strategies for the transfusion of subjects with complex red cell immunisation: the Bank of rare blood donors of the Region of Lombardy

    Science.gov (United States)

    Morelati, Fernanda; Arnaboldi, Piera; Barocci, Fiorella; Bodini, Umberto; Boiani, Elisa; Bresciani, Susanna; Cambiè, Giuseppe; Cazzaniga, Giovanni; Cocco, Ernesto; Copeta, Alessandro; Crotti, Massimo; D’Agostino, Francesco; D’Agostino, Marco; Focchiatti, Valeria; Fonti, Elena; Galassi, Luigi; Gazzola, Giambattista; Gelpi, Luigi; Greppi, Noemi; Inghilleri, Giovanni Battista; Isernia, Paola; Manera, Maria Cristina; Marini, Mirella; Monti, Rosalia; Morales, Rino; Moroni, Gianalessandro; Morra, Enrica; Pau, Maria Paola; Paccapelo, Cinzia; Pagliaro, Pasqualepaolo; Prati, Daniele; Revelli, Nicoletta; Rinaldini, Claudia; Rossi, Davide; Rossi, Fabio; Salvaneschi, Laura; Sciariada, Luca; Sergiacomo, Pierluigi; Tiburzi, Alessandra; Trotti, Roberta; Turdo, Rosalia; Velati, Claudio; Villa, Maria Antonietta; Vismara, Giuseppina; Vitali, Elisabetta; Marconi, Maurizio

    2007-01-01

    Introduction Selecting units of rare blood for transfusion to patients with complex immunisation is one of the most critical processes of a Transfusion Centre. In January 2005 the ‘Rare Blood Components Bank – Reference Centre of the Region of Lombardy’ w as established with the following goals: 1) identifying regional rare blood donors; 2) creating a regional registry of rare donors; 3) organising a regional bank of liquid and frozen rare blood units; 4) setting up a regional Immunohaematology Reference Laboratory (IRL) to type donors and resolve complex cases. Methods The key elements in establishing the Bank were periodic meetings organised by the directors and representatives of the regional Departments of Transfusion Medicine and Haematology (DTMH) and the institution of three working groups (informatics, regulations, finance). Results The regional IRL was set up, the relevant operating procedures were distributed region-wide, software features were defined and later validated upon activation, and the funds assigned were allocated to various cost items. The number and characteristics of the donors to be typed were identified and 14 regional DTMHs started to send samples. Overall, 20,714 donors were typed, for a total of 258,003 typings, and 2,880 rare donors were identified. Of these, 97% were rare donors because of combinations of antigens (2,139 negative for the S antigen and 659 negative for the s antigen) and 3% (n=82) because they were negative for high-frequency antigens. In the first 2 years of activity, the IRL carried out investigations of 140 complex cases referred from other Centres and distributed 2,024 units with rare phenotypes to 142 patients. Conclusions The main goal achieved in the first 24 months from the start of the project was to set up a regional network able to meet the transfusion needs of patients with complex immunisation. PMID:19204778

  9. Study on reducing red blood cell transfusion mechanism of Traditional Chinese Medicine%中医对减少红细胞输血作用的研究

    Institute of Scientific and Technical Information of China (English)

    陈震; 周俊; 韩聚强; 李捞摸; 张秋实; 王继升

    2014-01-01

    Objective: To explore the Chinese medicine to reduce red blood cell transfusion mechanism, anemia treatment and provide a theoretical basis for patients with severe hypoxic ischemic symptoms. Methods:in our hospital from 2012 May to 2013 May in our hospital were severe anemia in 96 cases, according to the order of admission, were randomly divided into study group(48 cases) and control group(48 cases), study group was treated with Chinese medicine Yiqi Buxue cream treatment, the control group using sugar iron injection treatment, treatment effects were compared between the two groups. Results:the treatment group the total effective rate was 97.9%in treatment group, the total effective rate was 87.5%, and there was significant difference between two groups(P<0.05). Study group Hb after treatment was (106.43±13.08) g/L, the control group after treatment Hb(98.69±14.25)g/L, there was significant difference between two groups(t=13.26, P<0.05). After treatment, study group MCV, MCH, MCHC improvement, compared with the control group with statistical significance;the two groups in the improvement of red blood cell morphology were obvious effect, and the study group was better than control group. Statistical significance of group SF after treatment and the control group at the same time difference(t=11.28, P<0.05). The control group had 10 cases of gastrointestinal discomfort, study group 1 cases of no adverse reaction. Conclusion:TCM symptoms of Chinese medicine Yiqi Buxue cream treatment can significantly improve the syndrome of blood deficiency of iron deficiency anemia, reduce the number and the number of red blood cell transfusion, clinical curative effect, less adverse reaction.%目的:探讨中医对减少红细胞输血作用机制,为重度贫血患者缺血缺氧症状治疗提供理论依据。方法:选择96例重度贫血患者,按照入院顺序号随机分成研究组与对照组,每组48例,研究组采用自拟中药益气补血膏治疗,

  10. Consequences of Transfusing Blood Components in Patients With Trauma: A Conceptual Model.

    Science.gov (United States)

    Jones, Allison R; Frazier, Susan K

    2017-04-01

    Transfusion of blood components is often required in resuscitation of patients with major trauma. Packed red blood cells and platelets break down and undergo chemical changes during storage (known as the storage lesion) that lead to an inflammatory response once the blood components are transfused to patients. Although some evidence supports a detrimental association between transfusion and a patient's outcome, the mechanisms connecting transfusion of stored components to outcomes remain unclear. The purpose of this review is to provide critical care nurses with a conceptual model to facilitate understanding of the relationship between the storage lesion and patients' outcomes after trauma; outcomes related to trauma, hemorrhage, and blood component transfusion are grouped according to those occurring in the short-term (≤30 days) and the long-term (>30 days). Complete understanding of these clinical implications is critical for practitioners in evaluating and treating patients given transfusions after traumatic injury.

  11. Complications of blood transfusion. How to recognize and respond to noninfectious reactions.

    Science.gov (United States)

    Sloop, G D; Friedberg, R C

    1995-07-01

    Severe transfusion reactions occur much less often than minor reactions, but it is difficult to discriminate clinically between impending severe reactions and minor reactions. Therefore, whenever a reaction occurs, the transfusion should be discontinued and a laboratory workup initiated to rule out an acute hemolytic transfusion reaction. At a minimum, a direct antiglobulin (Coombs') test should be performed, and specimens obtained before and after transfusion should be assayed for hemoglobinemia and hemoglobinuria. If the product transfused included red blood cells, then typing and crossmatching should be repeated on a posttransfusion blood specimen. Routine premedication with antipyretics is not recommended, since they may mask early signs and symptoms of more severe reactions and their efficacy is questionable. Recent insights into the mechanisms of transfusion reactions have suggested interventions that may help minimize or prevent potentially serious sequelae.

  12. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels;

    2009-01-01

    PURPOSE: We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 121 consecutive patients...... neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P .... CONCLUSION: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC....

  13. Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction.

    Science.gov (United States)

    Gupta, Sweta; Piefer, Cindy L; Fueger, Judy T; Johnson, Susan T; Punzalan, Rowena C

    2010-12-01

    A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction.

  14. Transfusion reaction in a case with the rare Bombay blood group

    Directory of Open Access Journals (Sweden)

    Hayedeh Javadzadeh Shahshahani

    2013-01-01

    Full Text Available Bombay phenotype is extremely rare in Caucasian with an incidence of 1 in 250,000. When individuals with the Bombay phenotype need blood transfusion, they can receive only autologous blood or blood from another Bombay blood group. Transfusing blood group O red cells to them can cause a fatal hemolytic transfusion reaction. In this study, we report a case with the rare Bombay blood group that was misdiagnosed as the O blood group and developed a hemolytic transfusion reaction. This highlights the importance of both forward and reverse typing in ABO blood grouping and standard cross-matching and performing standard pretransfusion laboratory tests in hospital blood banks.

  15. Transfusion reaction in a case with the rare Bombay blood group.

    Science.gov (United States)

    Shahshahani, Hayedeh Javadzadeh; Vahidfar, Mohamad Reza; Khodaie, Seyed Ali

    2013-01-01

    Bombay phenotype is extremely rare in Caucasian with an incidence of 1 in 250,000. When individuals with the Bombay phenotype need blood transfusion, they can receive only autologous blood or blood from another Bombay blood group. Transfusing blood group O red cells to them can cause a fatal hemolytic transfusion reaction. In this study, we report a case with the rare Bombay blood group that was misdiagnosed as the O blood group and developed a hemolytic transfusion reaction. This highlights the importance of both forward and reverse typing in ABO blood grouping and standard cross-matching and performing standard pretransfusion laboratory tests in hospital blood banks.

  16. Enhancing Transfusion Safety: Nurse’s Role

    Directory of Open Access Journals (Sweden)

    Kyriazi Vasiliki

    2011-01-01

    Full Text Available Background: Despite strict clinical measures, there are distinct steps in transfusion process which require acute attention.The nurse is responsible for insuring that the right unit is administered to the right patient. Knowledge of risks is essential toadminister and monitor transfusions safely.Aim: This study summarizes the available data concerning transfusion adverse events and provides theoretical and technicalaspects for improving transfusion practice.Methodology: A systematic review in PubMed, MedLine and MDConsult database was conducted. The research limitsincluded English texts, referring to transfusion risks and technological means aiming at transfusion safety.Results: Blood transfusion is a medical intervention that saves lives and improves the quality of life. The regulations forensuring the availability and assuring the quality of the blood component cannot avoid transfusion errors, placing patients atrisk. Most frequent errors are attributed to practitioners involved in the clinical transfusion process. Based on reports toSerious Hazards of Transfusion (SHOT the risk of transfusion error is estimated at 1:16,500. Over the last years severalcommittees have recommended guidance for enhancing the safety of blood ordering and administration. Moreover, newtechnology like barcode on patient wristband manages to improve the performance in each step.Conclusion: Safe transfusion process depends on a series of linked processes and nurses should take specific measuresreferring to pre- and post-transfusion stage. Technological innovations could help patients in need of transfusion therapy.

  17. Incompatible blood transfusion: Challenging yet lifesaving in the management of acute severe autoimmune hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Sudipta Sekhar Das

    2014-01-01

    Full Text Available Background and Aim: Autoimmune hemolytic anemia (AIHA is characterized by the production of autoantibodies directed against red cell antigens. Most patients of AIHA arrive in the emergency or out-patient department (OPD with severe anemia requiring urgent blood transfusion. Here we share our experience of managing these patients with incompatible blood transfusions and suggest the minimal test required to assure patient safety. Materials and Methods: A total of 14 patients admitted with severe anemia, diagnosed with AIHA and requiring blood transfusion urgently were included in the study. A series of immunohematological investigations were performed to confirm the diagnosis and issue "best match" packed red blood cells (PRBC to these patients. Results: A total of 167 PRBC units were crossmatched for 14 patients of which 46 units (28% were found to be best match ones and 26 (56.5% of these units were transfused. A mean turn around time of 222 min was observed in issuing the ′best match′ blood. Severe hemolysis was observed in all patients with a median hemoglobin increment of 0.88 g/dl after each unit PRBC transfusion. Conclusion: Decision to transfuse in AIHA should be based on the clinical condition of the patient. No critical patient should be denied blood transfusion due to serological incompatibility. Minimum investigations such as direct antiglobulin test (DAT, antibody screening and autocontrol should be performed to ensure transfusion safety in patients. All transfusion services should be capable of issuing "best match" PRBCs in AIHA.

  18. Detection of alloimmunization to ensure safer transfusion practice

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    Rashmi Sood

    2013-01-01

    Full Text Available Background: Serological safety is an integral part of overall safety for blood banks. Emphasis is on the use of routinue Red Blood Cell (RBC antibody screen test, at set time intervals, to reduce risks related to alloantibodies. Also emphasis is on importance of issuing antigen negative blood to alloantibody positive patients. Effect of using leucodepleted blood on the rate of alloimmunization is highlighted. The concept of provision of phenotypically matched blood is suggested. Materials and Methods: Antibody screen test is important to select appropriate blood for transfusion. Repeat antibody screen testing, except if time interval between the earlier and subsequent transfusion was less than 72 hours, followed by antibody identification, if required, was performed in patients being treated with repeat multiple blood transfusions. Between February 2008 and June 2009, repeat samples of 306 multi-transfused patients were analyzed. Search for irregular antibodies and reading of results was conducted using RBC panels (three-cell panel of Column Agglutination Technology (CAT and two cell panel of the Solid Phase Red Cell Adherence Technology (SPRCAT. Specificities of antibodies were investigated using appropriate panels, 11 cell panel of CAT and 16 cell panel of SPRCA. These technologies, detecting agglutination in columns and reactions in solid phase, evaluate the attachment of irregular incomplete antibody to antigen in the first phase of immunological reaction more directly and hence improve the reading of agglutination. Three to four log leuco reduced red blood cells were transfused to patients in the study using blood collection bags with integral filters. Results: Alloimmunization rate of 4.24% was detected from 306 multiply transfused patients tested and followed up. The Transfusion therapy may become significantly complicated. Conclusion: Red cell antibody screening and identification and subsequent issue of antigen negative blood have a

  19. Growth inhibiting effects of terazosin on androgen-independent prostate cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    许克新; 王向红; 凌明达; 王云川

    2003-01-01

    Objective To study the effects of an α1-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.Methods Two androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21WAF1 and p27KIP1.Results This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27KIP1.Conclusion This study provides evidence that the α1-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

  20. Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity.

    Science.gov (United States)

    Rouvier, E; Luciani, M F; Golstein, P

    1993-01-01

    Mechanisms of T cell-mediated cytotoxicity remain poorly defined at the molecular level. To investigate some of these mechanisms, we used as target cells, on the one hand, thymocytes from lpr and gld mouse mutants, and on the other hand, L1210 cells transfected or not with the apoptosis-inducing Fas molecule. These independent mutant or transfectant-based approaches both led to the conclusion that Fas was involved in the Ca(2+)-independent component of cytotoxicity mediated by at least two sources of T cells, namely nonantigen-specific in vitro activated hybridoma cells, and antigen-specific in vivo raised peritoneal exudate lymphocytes. Thus, in these cases, T cell-mediated cytotoxicity involved transduction via Fas of the target cell death signal.

  1. Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells.

    Directory of Open Access Journals (Sweden)

    Kosuke Kataoka

    Full Text Available Native cholera toxin (nCT as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs and nasal passages (NPs. Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs play a central role in the induction of B-1 B cell IgA class switch recombination (CSR for the enhancement of T cell-independent (TI mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ⁻/⁻ mice and wild-type mice given nasal trinitrophenyl (TNP-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA⁻ IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI.

  2. Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells.

    Science.gov (United States)

    Kataoka, Kosuke; Fujihashi, Keiko; Terao, Yutaka; Gilbert, Rebekah S; Sekine, Shinichi; Kobayashi, Ryoki; Fukuyama, Yoshiko; Kawabata, Shigetada; Fujihashi, Kohtaro

    2011-01-01

    Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell-independent (TI) mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ⁻/⁻ mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA⁻ IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI.

  3. Profile of Blood Transfusion Requests from Hospitals to Bandung Blood Transfusion Unit, Indonesian Red Cross in 2011

    Directory of Open Access Journals (Sweden)

    Syahla Nisaa Amalia

    2015-09-01

    Full Text Available Background: Blood transfusion as a part health services should be provided under appropriate indications and in a safe manner. In Indonesia, blood collection is run by the Blood Transfusion Unit of Indonesian Red Cross, where the blood is screened, processed into blood components, and finally distributed to hospitals. The purpose of this study was to describe the profile of blood transfusion requests from hospitals that do not have blood bank facility to the Bandung Blood Transfusion Unit, Indonesian Red Cross. Methods: A descriptive study was carried out using secondary data from Bandung Blood Transfusion Unit Indonesian Red Cross (UTD PMI Bandung. All blood request forms from hospitals during 2011 were collected and analyzed. Variables in this study were the amount of blood units, blood components, blood type, and indications of blood transfusion. Results: The number of blood units requested by hospitals were 35,841 units. The most blood units requested was in August 2011. The blood component requested was the packed red cell (61.1%, whole blood (17.4%, thrombocyte concentrate (10.6%, and fresh frozen plasma (7%. The total percentage of O, A, B and AB blood types were 36.1%, 28.6%, 27.5%, and 7.9% respectively. The most frequent indication for transfusion was anemia (61.7%, followed by surgery and other causes of bleeding. Conclusions: The total blood units requested by hospitals vary each month. The most blood component requested is Packed Red Cell and the type of blood is O blood type. The most frequent indication is anemia.

  4. LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6.

    Science.gov (United States)

    Ketscher, A; Jilg, C A; Willmann, D; Hummel, B; Imhof, A; Rüsseler, V; Hölz, S; Metzger, E; Müller, J M; Schüle, R

    2014-10-06

    Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.

  5. Pressure-aided transfusion of platelets: does it affect the platelets?

    DEFF Research Database (Denmark)

    Fischer-Nielsen, Anne; Stissing, Trine; Maansson, Charlotte;

    2010-01-01

    In massively bleeding patients, pressure infusers are used for transfusion of red blood cells and plasma but not for platelets (PLTs) due to an assumed negative effect on the PLTs. This study examined whether pressure-aided in vitro transfusion affected the number, activation state, and/or function...

  6. Modification of tumor growth by blood transfusion and perioperative procedures : a study in rats

    NARCIS (Netherlands)

    S.K. Singh

    1988-01-01

    textabstractA blood transfusion is a transplantation of all or part of the blood cells in the peripheral blood. The survival of grafted organ transplantation has been shown to be prolonged following blood transfusion. The mechanism is thought to be immunological in nature. The possibility of a relat

  7. Transfusion audit of blood products using the World Health Organization Basic Information Sheet in Qazvin, Islamic Republic of Iran.

    Science.gov (United States)

    Sheikholeslami, H; Kani, C; Fallah-Abed, P; Lalooha, F; Mohammadi, N

    2012-12-04

    We assessed the practicality of using the transfusion Basic Information Sheet (BIS) for data collection, to determine the overall adequacy of physician documentation of blood product transfusion, and to make an audit of the appropriateness of blood product transfusion. The transfusion process and clinical indications for transfusions administered to adult hospitalized patients in 3 tertiary care teaching hospitals in Qazvin were prospectively reviewed. Adequate documentation was achieved in 62.6% of all transfusion episodes, range 41%-73%, depending on the medical specialty; 15.7% of red blood cells and whole blood requests, 40.8% of platelet requests and 34.1% of fresh frozen plasma requests were inappropriate. BIS-based information along with data collection can be used to provide feedback regarding the effectiveness of and compliance with local and national transfusion guidelines.

  8. PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Tracy M Covey

    Full Text Available Porcupine (PORCN is a membrane-bound O-acyl transferase that is required for the palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for Wnt-Wntless (WLS binding, Wnt secretion, and Wnt signaling activity. We tested if PORCN was required for the proliferation of transformed cells. Knockdown of PORCN by multiple independent siRNAs results in a cell growth defect in a subset of epithelial cancer cell lines. The growth defect is transformation-dependent in human mammary epithelial (HMEC cells. Additionally, inducible PORCN knockdown by two independent shRNAs markedly reduces the growth of established MDA-MB-231 cancers in orthotopic xenografts in immunodeficient mice. Unexpectedly, the proliferation defect resulting from loss of PORCN occurs in a Wnt-independent manner, as it is rescued by re-expression of catalytically inactive PORCN, and is not seen after RNAi-mediated knockdown of the Wnt carrier protein WLS, nor after treatment with the PORCN inhibitor IWP. Consistent with a role in a Wnt-independent pathway, knockdown of PORCN regulates a distinct set of genes that are not altered by other inhibitors of Wnt signaling. PORCN protein thus appears to moonlight in a novel signaling pathway that is rate-limiting for cancer cell growth and tumorigenesis independent of its enzymatic function in Wnt biosynthesis and secretion.

  9. Transfusion related acute lung injury presenting with acute dyspnoea: a case report

    Directory of Open Access Journals (Sweden)

    Haji Altaf

    2008-10-01

    Full Text Available Abstract Introduction Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy. Case presentation We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours. Conclusion The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury.

  10. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells.

    Science.gov (United States)

    Poulin, Lionel Franz; Henri, Sandrine; de Bovis, Béatrice; Devilard, Elisabeth; Kissenpfennig, Adrien; Malissen, Bernard

    2007-12-24

    Langerhans cells (LCs) constitute a subset of dendritic cells (DCs) that express the lectin langerin and that reside in their immature state in epidermis. Paradoxically, in mice permitting diphtheria toxin (DT)-mediated ablation of LCs, epidermal LCs reappeared with kinetics that lagged behind that of their putative progeny found in lymph nodes (LNs). Using bone marrow (BM) chimeras, we showed that a major fraction of the langerin(+), skin-derived DCs found in LNs originates from a developmental pathway that is independent from that of epidermal LCs. This pathway, the existence of which was unexpected, originates in the dermis and gives rise to langerin(+) dermal DCs (DDCs) that should not be confused with epidermal LCs en route to LNs. It explains that after DT treatment, some langerin(+), skin-derived DCs reappear in LNs long before LC-derived DCs. Using CD45 expression and BrdU-labeling kinetics, both LCs and langerin(+) DDCs were found to coexist in wild-type mice. Moreover, DT-mediated ablation of epidermal LCs opened otherwise filled niches and permitted repopulation of adult noninflammatory epidermis with BM-derived LCs. Our results stress that the langerin(+) DC network is more complex than originally thought and have implications for the development of transcutaneous vaccines and the improvement of humanized mouse models.

  11. Blood transfusion in Europe: basic principles for initial and continuous training in transfusion medicine: an approach to an European harmonisation.

    Science.gov (United States)

    Mueller, M M; Seifried, E

    2006-11-01

    Over the past few decades, transfusion medicine and haemotherapy have evolved into complex medical disciplines comprising a broad field of subspecialties such as immunohaematology, blood component production, haemapheresis and haemostaseology. Transfusion medicine is thus an important qualification at the interfaces of analytical laboratory medicine, pharmaceutical production and clinical disciplines such as internal medicine, anaesthesiology or surgery. Physicians specialising in transfusion medicine are valuable and competent partners for these related disciplines when it comes to safe, effective and tailored haemotherapy. Why has transfusion medicine become so complex? On the one hand, one can discern problems such as infectious diseases like the HIV disaster in the past century, resulting in guidelines, directives and laws such as the transfusion law in Germany. Thereby, we now enjoy the highest level of blood product safety ever regarding viral transmission thanks to the broad implementation of PCR testing. On the other hand, there are numerous positive reasons for the increasing complexity of transfusion medicine: Modern medical therapies like stem cell transplantation, cellular therapy, transplantation of solid organs, regenerative medicine and surgery cannot exist without a safe supply of blood products and high quality standard as well as special blood products and laboratory services provided by blood banks and transfusion medicine specialists. Good laboratory practice (GLP), good manufacturing practice (GMP), quality management systems and quality control on the pharmaceutical manufacturer's level are only few examples of the standards in today's blood banking. European directives in the field of blood products, stem cell preparations and tissue have led to higher uniform quality standards for biological preparations in a unified Europe, which is the desired outcome, but which also increases the complexity of this field. In contrast, directives 93/16/EEC

  12. Blood Transfusion (For Parents)

    Science.gov (United States)

    ... or bleeding disorder , such as sickle cell disease , thalassemia, or anemia caused by kidney disease , hemophilia , or ... Kids For Parents MORE ON THIS TOPIC Beta Thalassemia Sickle Cell Disease Alpha Thalassemia von Willebrand Disease ...

  13. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells

    OpenAIRE

    2012-01-01

    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted...

  14. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

    Science.gov (United States)

    Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

    2006-02-01

    HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

  15. Calcium-independent phospholipase A₂, group VIA, is critical for RPE cell survival

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vohra, Rupali; Westlund, Barbro S.;

    2014-01-01

    PURPOSE: To investigate the significance of calcium-independent phospholipase A₂, group VIA (iPLA2-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures. METHODS: The human retinal pigment epithelium (RPE) cell line (ARPE-19) cells and primary mouse-RPE cultures were...... of iPLA₂-VIA after SI exposure. Inhibitors of iPLA₂-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA₂-VIA knockout mice and wild-type mice. The cultures were exposed to SI to investigate a possible increased protection against......-VIA-specific inhibitors in ARPE-19 cell cultures. RPE cultures from iPLA₂-VIA knockout mice were less vulnerable to SI-induced cell death compared to RPE cultures from wild-type mice. CONCLUSIONS: SI -induced RPE cell death involves iPLA₂-VIA upregulation and activation, and amelioration of SI...

  16. Direct antiglobulin test positivity in multi-transfused thalassemics

    Directory of Open Access Journals (Sweden)

    Ashish Jain

    2016-01-01

    Full Text Available Introduction: Red cell allo- and auto-immunization is a well recognized problem in multi-transfused thalassemic patients. We conducted this study on 301 multi-transfused thalassemic patients under the Thalassemia Transfusion Programme of Advanced Pediatric Centre of PGIMER. Aims and Objectives: The study was designed to determine the frequency of alloimmunization and autoimmunization in multi-transfused thalassemic patients and to establish the specificity of alloantibody to red cell antigens, if alloimmunization is detected. Materials and Methods: The antibody screening was performed by the conventional tube technique using commercially available three cell screening panel (Diamed Switzerland by saline, low ionic strength solution (LISS and albumin indirect antiglobulin test (IAT. Samples with alloantibodies were then tested with red cell identification panel to determine the alloantibody specificity. Autoantibody screening was performed by direct antiglobulin test (DAT during pre-transfusion testing. Results: Of the 301 patients, 52 (17.28% were found to have antibodies (-allo and –autoantibodies. A total of 11 red cell alloantibodies were detected in 10 patients and the specificities were anti-Kell in 6(54.5%, anti-D in 2(18.2%, anti-c in 1(9.1% and a combination of anti-E (9.1% and anti-Jkb in 1 (9.1% patients. DAT was positive in 48 (15.9% patients. The frequency of autoantibody was significantly higher in alloimmunized group as compared to non-alloimmunized group (60% V/s 14.4%. Also, the pre-transfusion hemoglobin was significantly lower in the immunized group (8.5 gm/dl V/s 9.0 gm/dl; p=0.03 than the non-immunized group. Conclusion: Based on these observations, we suggest antigen typing of all thalassemia major patients for ABO, Rh and Kell antigens before initiating transfusion therapy. Also, screening for allo- and auto-antibodies at regular intervals should be done prior to each transfusion.

  17. Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties.

    Science.gov (United States)

    Tong, Xinming; Yang, Fan

    2014-02-01

    Hydrogels have been widely used as artificial cell niche to mimic extracellular matrix with tunable properties. However, changing biochemical cues in hydrogels developed-to-date would often induce simultaneous changes in mechanical properties, which do not support mechanistic studies on stem cell-niche interactions. Here we report the development of a PEG-based interpenetrating network (IPN), which is composed of two polymer networks that can independently and simultaneously crosslink to form hydrogels in a cell-friendly manner. The resulting IPN hydrogel allows independently tunable biochemical and mechanical properties, as well as stable and more homogeneous presentation of biochemical ligands in 3D than currently available methods. We demonstrate the potential of our IPN platform for elucidating stem cell-niche interactions by modulating osteogenic differentiation of human adipose-derived stem cells. The versatility of such IPN hydrogels is further demonstrated using three distinct and widely used polymers to form the mechanical network while keeping the biochemical network constant.

  18. Anti-Kpa-induced severe delayed hemolytic transfusion reaction.

    Science.gov (United States)

    Koshy, R; Patel, B; Harrison, J S

    2009-01-01

    Kpa is a low-frequency antigen occurring in less than 2 percent of the Caucasian population. Mild to moderate delayed hemolytic transfusion reactions (DHTR) and hemolytic disease of the fetus and newborn attributable to anti-Kpa have been reported. Severe overt DHTR has not been reported with anti-Kpa. A case of a severe DHTR attributed to anti-Kpa after multiple RBC transfusions is being reported. A 52-year-old Caucasian woman received multiple units of RBCs for a lower gastrointestinal bleed. She was referred to our institution for hepatic and renal failure, which was supported by laboratory findings of peak LDH, bilirubin, BUN, and creatinine elevations. Hemoglobin had dropped on Day 10 after transfusion. The DAT and antibody screen (ABS) were negative. Initial workup and subsequent ABS were negative. Anti-Kpa was identified when an additional RBC panel was tested. One of the RBC units transfused was incompatible by antihuman globulin (AHG) crossmatch with the patient's plasma and typed positive for Kpa. DHTR was confirmed after extensive workup. The patient responded to supportive therapy and experienced an uneventful recovery. DHTR may not be considered when DAT and ABS are negative. However, correlation of recent transfusion with signs and symptoms should alert the clinician to entertain and investigate a DHTR that should include the AHG crossmatch of all implicated RBC units. The severity of the reaction also raises concerns as to when and what antigen specificity should be considered for inclusion in the antibody screening cells.

  19. Hemoglobin optimization and transfusion strategies in patients undergoing cardiac surgery

    Institute of Scientific and Technical Information of China (English)

    Mahdi; Najafi; David; Faraoni

    2015-01-01

    Although red blood cells(RBCs) transfusion is sometimes associated with adverse reactions,anemia could also lead to increased morbidity and mortality in highrisk patients. For these reasons,the definition of perioperative strategies that aims to detect and treat preoperative anemia,prevent excessive blood loss,and define "optimal" transfusion algorithms is crucial. Although the treatment with preoperative iron and erythropoietin has been recommended in some specific conditions,several controversies exist regarding the benefit-to-risk balance associated with these treatments. Further studies are needed to better define the indications,dosage,and route of administration for preoperative iron with or without erythropoietin supplementation. Although restrictive transfusion strategies in patients undergoing cardiac surgery have been shown to effectively reduce the incidence and the amount of RBCs transfusion without increase in side effects,some high-risk patients(e.g.,symptomatic acute coronary syndrome) could benefit from higher hemoglobin concentrations. Despite all efforts made last decade,a significant amount of work remains to be done to improve hemoglobin optimization and transfusion strategies in patients undergoing cardiac surgery.

  20. Soluble vascular endothelial growth factor in various blood transfusion components

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T;

    1999-01-01

    BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors....... The potential content of VEGF in various blood components for transfusion was evaluated. STUDY DESIGN AND METHODS: Soluble VEGF (sVEGF, isotype 165) was determined by an enzyme-linked immunosorbent assay (EIA) in serum and plasma samples and in lysed cells from healthy volunteers. Subsequently, total content...... of platelet-derived soluble plasminogen activator inhibitor type 1 (sPAI-1) was determined by an EIA in the same samples. Finally, the extracellular accumulation of sVEGF was determined in nonfiltered WB and SAGM blood during storage for 35 days and in BCP pools during storage for 7 days. RESULTS...

  1. Transplante autólogo de células-tronco hematopoiéticas sem uso de hemocomponentes Hematopoietic stem cell transplantation without the use of blood transfusions

    Directory of Open Access Journals (Sweden)

    Roberto L. Silva

    2006-06-01

    Full Text Available O transplante de células-tronco hematopoéticas (TCTH é terapia consolidada para tratamento de algumas doenças onco-hematológicas, e o suporte transfusional tem, tradicionalmente, sido fundamental para a realização do mesmo. Descrevemos um caso de paciente testemunha de Jeová, portadora de linfoma Hodgkin em terceira remissão parcial, que foi submetida a quimioterapia de altas doses com regime de condicionamento clássico (carmustina, etoposide, citarabina, melfalan e posterior infusão de células-tronco hematopoéticas sem o uso de hemocomponentes. A paciente apresentou toxicidade hematológica inerente ao procedimento e medidas clínicas de suporte tais como a utilização de eritropoetina, IL 11, antifibrinolítico, entre outras, foram utilizadas na tentativa de minimizar o risco de sangramento e anemia grave. O curso do transplante transcorreu sem complicações graves. Este caso demonstra que o transplante autólogo de células-tronco hematopoéticas sem o uso de hemocomponentes é factível em situações especiais, onde há clara expressão do desejo do paciente associado a condições clínicas favoráveis e acompanhamento médico especialista rigoroso.Hematopoietic stem cell transplantation (HSCT is standard therapy for the treatment of some hematological neoplasms and support with blood transfusions is considered essential for this procedure. Herein we describe the case of a Jeovah's witness who had Hodgkin's lymphoma in third partial remission and was submitted to high-dose chemotherapy using a classic conditioning regimen (carmustine, etoposide, cytarabine, melphalan with posterior infusion of autologous peripheral blood stem cells without the use of blood transfusions. The patient had the usual degree of hematological toxicity and was treated with clinical support measures, such as the use of erythropoietin, IL-11 and antifibrinolytics, with the goal of minimizing the risk of bleeding and serious anemia. The HSTC coursed

  2. Berberine induces caspase-independent cell death in colon tumor cells through activation of apoptosis-inducing factor.

    Directory of Open Access Journals (Sweden)

    Lihong Wang

    Full Text Available Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the mouse immorto-Min colonic epithelial (IMCE cells carrying the Apc(min mutation, and of normal colon epithelial cells, namely young adult mouse colonic epithelium (YAMC cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth.

  3. Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways.

    Science.gov (United States)

    Berkowska, Magdalena A; Driessen, Gertjan J A; Bikos, Vasilis; Grosserichter-Wagener, Christina; Stamatopoulos, Kostas; Cerutti, Andrea; He, Bing; Biermann, Katharina; Lange, Johan F; van der Burg, Mirjam; van Dongen, Jacques J M; van Zelm, Menno C

    2011-08-25

    Multiple distinct memory B-cell subsets have been identified in humans, but it remains unclear how their phenotypic diversity corresponds to the type of responses from which they originate. Especially, the contribution of germinal center-independent responses in humans remains controversial. We defined 6 memory B-cell subsets based on their antigen-experienced phenotype and differential expression of CD27 and IgH isotypes. Molecular characterization of their replication history, Ig somatic hypermutation, and class-switch profiles demonstrated their origin from 3 different pathways. CD27⁻IgG⁺ and CD27⁺IgM⁺ B cells are derived from primary germinal center reactions, and CD27⁺IgA⁺ and CD27⁺IgG⁺ B cells are from consecutive germinal center responses (pathway 1). In contrast, natural effector and CD27⁻IgA⁺ memory B cells have limited proliferation and are also present in CD40L-deficient patients, reflecting a germinal center-independent origin. Natural effector cells at least in part originate from systemic responses in the splenic marginal zone (pathway 2). CD27⁻IgA⁺ cells share low replication history and dominant Igλ and IgA2 use with gut lamina propria IgA+ B cells, suggesting their common origin from local germinal center-independent responses (pathway 3). Our findings shed light on human germinal center-dependent and -independent B-cell memory formation and provide new opportunities to study these processes in immunologic diseases.

  4. NOTE: Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

    Science.gov (United States)

    van Gemert, Martin J. C.; van den Wijngaard, Jeroen P. H. M.; Lopriore, Enrico; Pasman, Suzanne A.; Vandenbussche, Frank P. H. A.

    2008-04-01

    Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others.

  5. Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

    Energy Technology Data Exchange (ETDEWEB)

    Gemert, Martin J C van; Wijngaard, Jeroen P H M van den [Laser Centre and Department of Obstetrics, Laser Center, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Lopriore, Enrico [Division of Neonatology, Department of Pediatrics, Leiden University Medical Centre, Leiden (Netherlands); Pasman, Suzanne A; Vandenbussche, Frank P H A [Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Centre, Leiden (Netherlands)], E-mail: m.j.vangemert@amc.uva.nl

    2008-04-07

    Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others. (note)

  6. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  7. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  8. Polyamines regulate cell growth and cellular methylglyoxal in high-glucose medium independently of intracellular glutathione.

    Science.gov (United States)

    Kwak, Min-Kyu; Lee, Mun-Hyoung; Park, Seong-Jun; Shin, Sang-Min; Liu, Rui; Kang, Sa-Ouk

    2016-03-01

    Polyamines can presumably inhibit protein glycation, when associated with the methylglyoxal inevitably produced during glycolysis. Herein, we hypothesized a nonenzymatic interaction between putrescine and methylglyoxal in putrescine-deficient or -overexpressing Dictyostelium cells in high-glucose medium, which can control methylglyoxal production. Putrescine was essentially required for growth rescue accompanying methylglyoxal detoxification when cells underwent growth defect and cell cycle G1-arrest when supplemented with high glucose. Furthermore, methylglyoxal regulation by putrescine seemed to be a parallel pathway independent of the changes in cellular glutathione content in high-glucose medium. Consequently, we suggest that Dictyostelium cells need polyamines for normal growth and cellular methylglyoxal regulation.

  9. Adaptation of mammalian auditory hair cell mechanotransduction is independent of calcium entry.

    Science.gov (United States)

    Peng, Anthony W; Effertz, Thomas; Ricci, Anthony J

    2013-11-20

    Adaptation is a hallmark of hair cell mechanotransduction, extending the sensory hair bundle dynamic range while providing mechanical filtering of incoming sound. In hair cells responsive to low frequencies, two distinct adaptation mechanisms exist, a fast component of debatable origin and a slow myosin-based component. It is generally believed that Ca(2+) entry through mechano-electric transducer channels is required for both forms of adaptation. This study investigates the calcium dependence of adaptation in the mammalian auditory system. Recordings from rat cochlear hair cells demonstrate that altering Ca(2+) entry or internal Ca(2+) buffering has little effect on either adaptation kinetics or steady-state adaptation responses. Two additional findings include a voltage-dependent process and an extracellular Ca(2+) binding site, both modulating the resting open probability independent of adaptation. These data suggest that slow motor adaptation is negligible in mammalian auditory cells and that the remaining adaptation process is independent of calcium entry.

  10. Blood genotyping for improved outcomes in chronic transfusion patients: current and future perspectives

    Directory of Open Access Journals (Sweden)

    Kutner JM

    2014-09-01

    Full Text Available Jose Mauro Kutner,1 Mariza Mota,1 Fabiana Conti,1 Lilian Castilho1,2 1Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 2Hemocentro Unicamp, Campinas, SP, Brazil Abstract: Blood transfusions are life sustaining in chronically transfused patients. However, certain complications, such as alloimmunization to red blood cells, can create challenges in the management of those patients. Routine phenotyping of blood recipients and the use of phenotype-matched blood units for transfusion have been useful to lower the occurrence of red cell alloantibodies in chronically transfused individuals. Nevertheless, extensive phenotyping is expensive, laborious, and cannot be performed in certain situations. The molecular understanding of blood groups has enabled the design of assays that may be used to better guide matched red blood cell transfusions. This review summarizes key findings related to red cell alloimmunization, the already identified and potential future benefits of blood group genotyping, and how molecular typing is being incorporated in the blood bank's routine to improve clinical and long-term outcomes in chronically transfused patients. Keywords: blood group genotyping, chronically transfused patients, platelet genotyping, RBC alloimmunization

  11. Role of Ca2+-independent phospholipase A2 in cell growth and signaling

    OpenAIRE

    Hooks, Shelley B; Cummings, Brian S.

    2008-01-01

    Phospholipase A2(PLA2) are esterases that cleave glycerophospholipids to release fatty acids and lysophospholipids. Several studies demonstrate that PLA2 regulate growth and signaling in several cell types. However, few of these studies have focused on Ca2+-independent phospholipase A2(iPLA2 or Group VI PLA2). This class of PLA2 was originally suggested to mediate phospholipid remodeling in several cell types including macrophages. As such, it was labeled as a housekeeping protein and thought...

  12. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  13. Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Curry, Merril C.; Peters, Amelia A. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Kenny, Paraic A. [Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Roberts-Thomson, Sarah J. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Monteith, Gregory R., E-mail: gregm@uq.edu.au [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia)

    2013-05-10

    Highlights: •Some clinical breast cancers are associated with MCU overexpression. •MCU silencing did not alter cell death initiated with the Bcl-2 inhibitor ABT-263. •MCU silencing potentiated caspase-independent cell death initiated by ionomycin. •MCU silencing promoted ionomycin-mediated cell death without changes in bulk Ca{sup 2+}. -- Abstract: The mitochondrial calcium uniporter (MCU) transports free ionic Ca{sup 2+} into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca{sup 2+} levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca{sup 2+} levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

  14. Efficacy and Safety of Frozen Blood for Transfusion in Trauma Patients - A Multi-Center Trial

    Science.gov (United States)

    2015-04-01

    shown to be a major risk factor for post-injury multiple organ failure [24,26,27,29,46,47]. Koch et al. found associations between age of blood...of stay, acute respiratory distress syndrome, acute renal failure, transfusion reaction, deep venous thrombosis , and mortality) were recorded. Acute...Blackwell J, Ciesla DJ, et al. Age of transfused blood is an independent risk factor for postinjury multiple organ failure. Am J Surg. 1999; 178(6):570

  15. PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells.

    Science.gov (United States)

    Jilg, Cordula A; Ketscher, Anett; Metzger, Eric; Hummel, Barbara; Willmann, Dominica; Rüsseler, Vanessa; Drendel, Vanessa; Imhof, Axel; Jung, Manfred; Franz, Henriette; Hölz, Stefanie; Krönig, Malte; Müller, Judith M; Schüle, Roland

    2014-12-30

    The major threat in prostate cancer is the occurrence of metastases in androgen-independent tumor stage, for which no causative cure is available. Here we show that metastatic behavior of androgen-independent prostate tumor cells requires the protein-kinase-C-related kinase (PRK1/PKN1) in vitro and in vivo. PRK1 regulates cell migration and gene expression through its kinase activity, but does not affect cell proliferation. Transcriptome and interactome analyses uncover that PRK1 regulates expression of migration-relevant genes by interacting with the scaffold protein sperm-associated antigen 9 (SPAG9/JIP4). SPAG9 and PRK1 colocalize in human cancer tissue and are required for p38-phosphorylation and cell migration. Accordingly, depletion of either ETS domain-containing protein Elk-1 (ELK1), an effector of p38-signalling or p38 depletion hinders cell migration and changes expression of migration-relevant genes as observed upon PRK1-depletion. Importantly, a PRK1 inhibitor prevents metastases in mice, showing that the PRK1-pathway is a promising target to hamper prostate cancer metastases in vivo. Here we describe a novel mechanism controlling the metastatic behavior of PCa cells and identify PRK1 as a promising therapeutic target to treat androgen-independent metastatic prostate cancer.

  16. CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression.

    Directory of Open Access Journals (Sweden)

    Selena Viganò

    2014-09-01

    Full Text Available Expression of co-inhibitory molecules is generally associated with T-cell dysfunction in chronic viral infections such as HIV or HCV. However, their relative contribution in the T-cell impairment remains unclear. In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+ CD8 T cells may be independent of PD-1 expression. The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+ CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression.

  17. Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Curry, Merril C; Peters, Amelia A; Kenny, Paraic A; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2013-05-10

    The mitochondrial calcium uniporter (MCU) transports free ionic Ca(2+) into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca(2+) levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca(2+) levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

  18. LIGHT/TNFSR14 can regulate hepatic lipase expression by hepatocytes independent of T cells and Kupffer cells.

    Directory of Open Access Journals (Sweden)

    Bijoy Chellan

    Full Text Available LIGHT/TNFSF14 is a costimulatory molecule expressed on activated T cells for activation and maintenance of T cell homeostasis. LIGHT over expressed in T cells also down regulates hepatic lipase levels in mice through lymphotoxin beta receptor (LTβR signaling. It is unclear whether LIGHT regulates hepatic lipase directly by interacting with LTβR expressing cells in the liver or indirectly by activation of T cells, and whether Kupffer cells, a major cell populations in the liver that expresses the LTβR, are required. Here we report that LIGHT expression via an adenoviral vector (Ad-LIGHT is sufficient to down regulate hepatic lipase expression in mice. Depletion of Kupffer cells using clodronate liposomes had no effect on LIGHT-mediated down regulation of hepatic lipase. LIGHT-mediated regulation of hepatic lipase is also independent of LIGHT expression by T cells or activation of T cells. This is demonstrated by the decreased hepatic lipase expression in the liver of Ad-LIGHT infected recombination activating gene deficient mice that lack mature T cells and by the Ad-LIGHT infection of primary hepatocytes. Hepatic lipase expression was not responsive to LIGHT when mice lacking LTβR globally or only on hepatocytes were infected with Ad-LIGHT. Therefore, our data argues that interaction of LIGHT with LTβR on hepatocytes, but not Kupffer cells, is sufficient to down regulate hepatic lipase expression and that this effect can be independent of LIGHT's costimulatory function.

  19. Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sunga [Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747 (Korea, Republic of); Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Gangwon-do, 200701 (Korea, Republic of); Kim, Ki Mo [Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM), 305811, Daejeon (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Gangwon-do, 200701 (Korea, Republic of)

    2011-12-15

    Cordycepin (3-deoxyadenosine), found in Cordyceps spp., has been known to have many therapeutic effects including immunomodulatory, anti-inflammatory, antimicrobial, and anti-aging effects. Moreover, anti-tumor and anti-metastatic effects of cordycepin have been reported, but the mechanism causing cancer cell death is poorly characterized. The present study was designed to investigate whether the mechanisms of cordycepin-induced cell death were associated with estrogen receptor in breast cancer cells. Exposure of both MDA-MB-231 and MCF-7 human breast cancer cells to cordycepin resulted in dose-responsive inhibition of cell growth and reduction in cell viability. The cordycepin-induced cell death in MDA-MB-231 cells was associated with several specific features of the mitochondria-mediated apoptotic pathway, which was confirmed by DNA fragmentation, TUNEL, and biochemical assays. Cordycepin also caused a dose-dependent increase in mitochondrial translocation of Bax, triggering cytosolic release of cytochrome c and activation of caspases-9 and -3. Interestingly, MCF-7 cells showed autophagy-associated cell death, as observed by the detection of an autophagosome-specific protein and large membranous vacuole ultrastructure morphology in the cytoplasm. Cordycepin-induced autophagic cell death has applications in treating MCF-7 cells with apoptotic defects, irrespective of the ER response. Although autophagy has a survival function in tumorigenesis of some cancer cells, autophagy may be important for cordycepin-induced MCF-7 cell death. In conclusion, the results of our study demonstrate that cordycepin effectively kills MDA-MB-231 and MCF-7 human breast cancer cell lines in culture. Hence, further studies should be conducted to determine whether cordycepin will be a clinically useful, ER-independent, chemotherapeutic agent for human breast cancer. -- Highlights: Black-Right-Pointing-Pointer We studied the mechanism which cordycepin-induced cell death association with

  20. SAP-Dependent and -Independent Regulation of Innate T Cell Development Involving SLAMF Receptors.

    Science.gov (United States)

    De Calisto, Jaime; Wang, Ninghai; Wang, Guoxing; Yigit, Burcu; Engel, Pablo; Terhorst, Cox

    2014-01-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF) of receptors, whose expression is essential for T, NK, and B-cell responses. Additionally, the expression of SAP in double-positive thymocytes is mandatory for natural killer T (NKT) cells and, in mouse, for innate CD8(+) T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Slamf6, have been shown to positively cooperate during NKT cell differentiation in mouse. However, it is less clear whether other members of this family may also participate in the development of these innate T cells. Here, we show that Slamf[1 + 6](-/-) and Slamf[1 + 5 + 6](-/-) B6 mice have ~70% reduction of NKT cells compared to wild-type B6 mice. Unexpectedly, the proportion of innate CD8(+) T cells slightly increased in the Slamf[1 + 5 + 6](-/-) , but not in the Slamf[1 + 6](-/-) strain, suggesting that Slamf5 may function as a negative regulator of innate CD8(+) T cell development. Accordingly, Slamf5(-/-) B6 mice showed an exclusive expansion of innate CD8(+) T cells, but not NKT cells. Interestingly, the SAP-independent Slamf7(-/-) strain showed an expansion of both splenic innate CD8(+) T cells and thymic NKT cells. On the other hand, and similar to what was recently shown in Slamf3(-/-) BALB/c mice, the proportions of thymic promyelocytic leukemia zinc finger (PLZF(hi)) NKT cells and innate CD8(+) T cells significantly increased in the SAP-independent Slamf8(-/-) BALB/c strain. In summary, these results show that NKT and innate CD8(+) T cell development can be regulated in a SAP-dependent and -independent fashion by SLAMF receptors, in which Slamf1, Slamf6, and Slamf8 affect development of NKT cells, and that Slamf5, Slamf7, and Slamf8 affect the development of innate CD8(+) T cells.

  1. SAP-independent and -dependent regulation of innate T cell development involving SLAMF receptors

    Directory of Open Access Journals (Sweden)

    Jaime eDe Calisto

    2014-04-01

    Full Text Available Signaling lymphocytic activation molecule (SLAM-associated protein (SAP plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF of receptors, whose expression is essential for T, NK, and B cell responses. Additionally, the expression of SAP in double-positive (DP thymocytes is mandatory for natural killer T (NKT cells and, in mouse, for innate CD8+ T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Slamf6, have been shown to positively cooperate during NKT cell differentiation in mouse. However, it is less clear whether other members of this family may also participate in the development of these innate T cells. Here, we show that Slamf[1+6]-/- and Slamf[1+5+6]-/- B6 mice have an approximately 70% reduction of NKT cells compared to wild-type (WT B6 mice. Unexpectedly, the proportion of innate CD8+ T cells slightly increased in the Slamf[1+5+6]-/-, but not in the Slamf[1+6]-/- strain, suggesting that Slamf5 may function as a negative regulator of innate CD8+ T cell development. Accordingly, Slamf5-/- B6 mice showed an exclusive expansion of innate CD8+ T cells, but not NKT cells. Interestingly, the SAP-independent Slamf7-/- strain showed an expansion of both splenic innate CD8+ T cells and thymic NKT cells. On the other hand, and similar to what was recently shown in Slamf3-/- BALB/c mice, the proportions of thymic PLZFhi NKT cells and innate CD8+ T cells significatively increased in the SAP-independent Slamf8-/- BALB/c strain. In summary, these results show that NKT and innate CD8+ T cell development can be regulated in a SAP-dependent and -independent fashion by SLAMF receptors, in which Slamf1, Slamf6, and Slamf8 affect development of NKT cells, and that Slamf5, Slamf7, and Slamf8 affect the development of innate CD8+ T cells.

  2. Cell adhesion molecules regulate contractile ring-independent cytokinesis in Dictyostelium discoideum

    Institute of Scientific and Technical Information of China (English)

    Akira Nagasaki; Masamitsu Kanada; Taro QP Uyeda

    2009-01-01

    To investigate the roles of substrate adhesion in cytokinesis, we established cell lines lacking paxiUin (PAXB) or vinculin (VINA), and those expressing the respective GFP fusion proteins in Dictyostelium discoideum. As in mammalian cells, GFP-PAXB and GFP-VINA formed focal adhesion-like complexes on the cell bottom, paxB cells in suspension grew normally, but on substrates, often failed to divide after regression of the furrow. The efficient cytokinesis of paxB cells in suspension is not because of shear forces to assist abscission, as they divided normally in static suspension culture as well. Double knockout strains lacking mhcA, which codes for myosin I1, and paxB or vinA displayed more severe cytokinetic defects than each single knockout strain. In mitotic wild-type cells, GFP-PAXB was diffusely distributed on the basal membrane, but was strikingly condensed along the polar edges in mitotic mhcA cells. These results are consistent with our idea that Dictyostelium displays two forms of cytokinesis, one that is contractile ringdependent and adhesion-independent, and the other that is contractile ring-independent and adhesion-dependent, and that the latter requires PAXB and VINA. Furthermore, that paxB cells fail to divide normally in the presence of substrate adhesion suggests that this adhesion molecule may play additional signaling roles.

  3. A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

    Directory of Open Access Journals (Sweden)

    Joshua W Modell

    2014-10-01

    Full Text Available Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.

  4. A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

    Science.gov (United States)

    Modell, Joshua W; Kambara, Tracy K; Perchuk, Barrett S; Laub, Michael T

    2014-10-01

    Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.

  5. Advantage of autologous blood transfusion in surgery for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yoshito Tomimaru; Hiroaki Nagano; Hidetoshi Eguchi; Shigeru Marubashi; Hiroshi Wada; Shogo Kobayashi; Masahiro Tanemura; Koji Umeshita; Yuichiro Doki; Masaki Mori

    2011-01-01

    AIM: To evaluate the significance of autologous blood transfusion (AT) in reducing homologous blood trans-fusion (HT) in surgery for hepatocellular carcinoma (HCC).METHODS: The proportion of patients who received HT was compared between two groups determined by the time of AT introduction; period A (1991-1994, n = 93) and period B (1995-2000, n = 201). Multivariate logistic regression analysis was performed in order to identify independent significant predictors of the need for HT. We also investigated the impact of AT and HT on long-term postoperative outcome after curative sur-gery for HCC.RESULTS: The proportion of patients with HT was significantly lower in period B than period A (18.9% vs 60.2%, P < 0.0001). Multivariate logistic regression analysis identified AT administration as a significant independent predictor of the need for HT (P < 0.0001). Disease-free survival in patients with AT was com-parable to that without any transfusion. Multivariate analysis identified HT administration as an independent significant factor for poorer disease-free survival (P = 0.0380).CONCLUSION: AT administration significantly de-creased the need for HT. Considering the postoperative survival disadvantage of HT, AT administration could improve the long-term outcome of HCC patients.

  6. Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation.

    Directory of Open Access Journals (Sweden)

    Hongkai Ji

    Full Text Available The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP, global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs. We further document that a Myc core signature (MCS set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells.

  7. Analysis of Leakage Reduction Techniques in Independent-Gate DG FinFET SRAM Cell

    Directory of Open Access Journals (Sweden)

    Vandna Sikarwar

    2013-01-01

    Full Text Available Scaling of devices in bulk CMOS technology leads to short-channel effects and increase in leakage. Static random access memory (SRAM is expected to occupy 90% of the area of SoC. Since leakage becomes the major factor in SRAM cell, it is implemented using FinFET. Further, double-gate FinFET devices became a better choice for deep submicron technologies. With this consideration in our research work, 6T SRAM cell is implemented using independent-gate DG FinFET in which both the opposite sides of gates are controlled independently which provides better scalability to the SRAM cell. The device is implemented using different leakage reduction techniques such as gated-Vdd technique and multithreshold voltage technique to reduce leakage. Therefore, power consumption in the SRAM cell is reduced and provides better performance. Independent-gate FinFET SRAM cell using various leakage reduction techniques has been simulated using Cadence virtuoso tool in 45 nm technology.

  8. Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

    Science.gov (United States)

    Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

    2016-01-01

    Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

  9. Effects of massive transfusion on oxygen availability

    Directory of Open Access Journals (Sweden)

    José Otávio Costa Auler Jr

    Full Text Available OBJECTIVE: To determine oxygen derived parameters, hemodynamic and biochemical laboratory data (2,3 Diphosphoglycerate, lactate and blood gases analysis in patients after cardiac surgery who received massive blood replacement. DESIGN: Prospective study. SETTING: Heart Institute (Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brazil. PARTICIPANTS: Twelve patients after cardiac surgery who received massive transfusion replacement; six of them evolved to a fatal outcome within the three-day postoperative follow-up. MEASUREMENTS AND MAIN RESULTS: The non-survivors group (n=6 presented high lactate levels and low P50 levels, when compared to the survivors group (p<0.05. Both groups presented an increase in oxygen consumption and O2 extraction, and there were no significant differences between them regarding these parameters. The 2,3 DPG levels were slightly reduced in both groups. CONCLUSIONS: This study shows that patients who are massively transfused following cardiovascular surgery present cell oxygenation disturbances probably as a result of O2 transport inadequacy.

  10. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle;

    1999-01-01

    -assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

  11. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin

    OpenAIRE

    2015-01-01

    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34+ hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex...

  12. Hepatic Cell Apoptosis Was Triggerred by HBx Accumulation and Independent on Verapamil

    Institute of Scientific and Technical Information of China (English)

    王海平; 陈孝平; 白祥军

    2004-01-01

    Summary: In order to studythe roles of HBx and calcium inhibitor verapamil in apoptosis of human normal hepatic cells, L02-off, a pTet-off stably integrated human hepatic cell line was established,in which HBx expression was tightly induced by Doxycycline. The effect of different amounts of HBx and verapamil on apoptosis of human normal hepatic cells was detected. The study showed that apoptosis was triggered by accumulation of intracellular HBx, while verapamil had no effects on the apoptotic process. It was concluded that apoptosis mediated by HBx was dose-dependent but calcium-independent.

  13. Mammalian cryptochromes impinge on cell cycle progression in a circadian clock-independent manner.

    Science.gov (United States)

    Destici, Eugin; Oklejewicz, Małgorzata; Saito, Shoko; van der Horst, Gijsbertus T J

    2011-11-01

    By gating cell cycle progression to specific times of the day, the intracellular circadian clock is thought to reduce the exposure of replicating cells to potentially hazardous environmental and endogenous genotoxic compounds. Although core clock gene defects that eradicate circadian rhythmicity can cause an altered in vivo genotoxic stress response and aberrant proliferation rate, it remains to be determined to what extent these cell cycle related phenotypes are due to a cell-autonomous lack of circadian oscillations. We investigated the DNA damage sensitivity and proliferative capacity of cultured primary Cry1(-/- )|Cry2(-/-) fibroblasts. Contrasting previous in vivo studies, we show that the absence of CRY proteins does not affect the cell-autonomous DNA damage response upon exposure of primary cells in vitro to genotoxic agents, but causes cells to proliferate faster. By comparing primary wild-type, Cry1(-/-) |Cry2(-/-), Cry1(+/-)|Cry2(-/-) and Cry1(-/-)|Cry2(+/-) fibroblasts, we provide evidence that CRY proteins influence cell cycle progression in a cell-autonomous, but circadian clock-independent manner and that the accelerated cell cycle progression of Cry-deficient cells is caused by global dysregulation of Bmal1-dependent gene expression. These results suggest that the inconsistency between in vivo and in vitro observations might be attributed to systemic circadian control rather than a direct cell-autonomous control.

  14. Telomerase inhibition targets clonogenic multiple myeloma cells through telomere length-dependent and independent mechanisms.

    Directory of Open Access Journals (Sweden)

    Sarah K Brennan

    Full Text Available BACKGROUND: Plasma cells constitute the majority of tumor cells in multiple myeloma (MM but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC. These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities. METHODOLOGY/PRINCIPAL FINDINGS: Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1 as revealed by quantitative real-time PCR. CONCLUSIONS: Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms.

  15. Transfusion-transmitted parasitic infections

    Directory of Open Access Journals (Sweden)

    Singh Gagandeep

    2010-01-01

    Full Text Available The transmission of parasitic organisms through transfusion is relatively rare. Of the major transfusion-transmitted diseases, malaria is a major cause of TTIP in tropical countries whereas babesiosis and Chagas′ disease pose the greatest threat to donors in the USA In both cases, this is due to the increased number of potentially infected donors. There are no reliable serologic tests available to screen donors for any of these organisms and the focus for prevention remains on adherence to donor screening guidelines that address travel history and previous infection with the etiologic agent. One goal is the development of tests that are able to screen for and identify donors potentially infectious for parasitic infections without causing the deferral of a large number of non-infectious donors or significantly increasing costs. Ideally, methods to inactivate the infectious organism will provide an element of added safety to the blood supply.

  16. In vitro human embryonic stem cell hematopoiesis mimics MYB-independent yolk sac hematopoiesis.

    Science.gov (United States)

    Vanhee, Stijn; De Mulder, Katrien; Van Caeneghem, Yasmine; Verstichel, Greet; Van Roy, Nadine; Menten, Björn; Velghe, Imke; Philippé, Jan; De Bleser, Dominique; Lambrecht, Bart N; Taghon, Tom; Leclercq, Georges; Kerre, Tessa; Vandekerckhove, Bart

    2015-02-01

    Although hematopoietic precursor activity can be generated in vitro from human embryonic stem cells, there is no solid evidence for the appearance of multipotent, self-renewing and transplantable hematopoietic stem cells. This could be due to short half-life of hematopoietic stem cells in culture or, alternatively, human embryonic stem cell-initiated hematopoiesis may be hematopoietic stem cell-independent, similar to yolk sac hematopoiesis, generating multipotent progenitors with limited expansion capacity. Since a MYB was reported to be an excellent marker for hematopoietic stem cell-dependent hematopoiesis, we generated a MYB-eGFP reporter human embryonic stem cell line to study formation of hematopoietic progenitor cells in vitro. We found CD34(+) hemogenic endothelial cells rounding up and developing into CD43(+) hematopoietic cells without expression of MYB-eGFP. MYB-eGFP(+) cells appeared relatively late in embryoid body cultures as CD34(+)CD43(+)CD45(-/lo) cells. These MYB-eGFP(+) cells were CD33 positive, proliferated in IL-3 containing media and hematopoietic differentiation was restricted to the granulocytic lineage. In agreement with data obtained on murine Myb(-/-) embryonic stem cells, bright eGFP expression was observed in a subpopulation of cells, during directed myeloid differentiation, which again belonged to the granulocytic lineage. In contrast, CD14(+) macrophage cells were consistently eGFP(-) and were derived from eGFP-precursors only. In summary, no evidence was obtained for in vitro generation of MYB(+) hematopoietic stem cells during embryoid body cultures. The observed MYB expression appeared late in culture and was confined to the granulocytic lineage.

  17. Independent regulation of tumor cell migration by matrix stiffness and confinement

    Science.gov (United States)

    Pathak, Amit; Kumar, Sanjay

    2012-01-01

    Tumor invasion and metastasis are strongly regulated by biophysical interactions between tumor cells and the extracellular matrix (ECM). While the influence of ECM stiffness on cell migration, adhesion, and contractility has been extensively studied in 2D culture, extension of this concept to 3D cultures that more closely resemble tissue has proven challenging, because perturbations that change matrix stiffness often concurrently change cellular confinement. This coupling is particularly problematic given that matrix-imposed steric barriers can regulate invasion speed independent of mechanics. Here we introduce a matrix platform based on microfabrication of channels of defined wall stiffness and geometry that allows independent variation of ECM stiffness and channel width. For a given ECM stiffness, cells confined to narrow channels surprisingly migrate faster than cells in wide channels or on unconstrained 2D surfaces, which we attribute to increased polarization of cell-ECM traction forces. Confinement also enables cells to migrate increasingly rapidly as ECM stiffness rises, in contrast with the biphasic relationship observed on unconfined ECMs. Inhibition of nonmuscle myosin II dissipates this traction polarization and renders the relationship between migration speed and ECM stiffness comparatively insensitive to matrix confinement. We test these hypotheses in silico by devising a multiscale mathematical model that relates cellular force generation to ECM stiffness and geometry, which we show is capable of recapitulating key experimental trends. These studies represent a paradigm for investigating matrix regulation of invasion and demonstrate that matrix confinement alters the relationship between cell migration speed and ECM stiffness. PMID:22689955

  18. Bupivacaine induces apoptosis through caspase-dependent and -independent pathways in canine mammary tumor cells.

    Science.gov (United States)

    Chiu, Yi-Shu; Cheng, Yeong-Hsiang; Lin, Sui-Wen; Chang, Te-Sheng; Liou, Chian-Jiun; Lai, Yu-Shen

    2015-06-01

    Local anesthetics have been reported to induce apoptosis in various cell lines. In this study, we showed that bupivacaine also induced apoptosis in DTK-SME cells, a vimentin(+)/AE1(+)/CK7(+)/HSP27(+), tumorigenic, immortalized, canine mammary tumor cell line. Bupivacaine induced apoptosis in DTK-SME cells in a time- and concentration-dependent manner. Apoptosis-associated morphological changes, including cell shrinkage and rounding, chromatin condensation, and formation of apoptotic bodies, were observed in the bupivacaine-treated DTK-SME cells. Apoptosis was further confirmed with annexin V staining, TUNEL staining, and DNA laddering assays. At the molecular level, the activation of caspases-3, -8, and -9 corresponded well to the degree of DNA fragmentation triggered by bupivacaine. We also demonstrated that the pan-caspase inhibitor, z-VAD-fmk, only partially inhibited the apoptosis induced by bupivacaine. Moreover, treated cells increased expression of endonuclease G, a death effector that acts independently of caspases. Our data suggested that bupivacaine-induced apoptosis occurs through both caspase-dependent and caspase-independent apoptotic pathways.

  19. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

    Science.gov (United States)

    Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

    2015-01-01

    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential.

  20. Effect of miR-296 on the Apoptosis of Androgen-independent Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Pei CHENG; Run-sheng LI; Biao-yang LIN; Wei-qun WANG; Yu-hua LI; Yan GUO; Wei LI

    2009-01-01

    Objective To investigate the miR-296's function in prostate carcinoma(PCa) cells. Methods In order to profile the miRNA expression in LNCaP cells, the cultured cells were stimulated with androgen after 48-h starvation, miRNA microarray analysis and Q-RT-PCR assay were performed. To characterize the effects of miR296 on PCa cells, CL-1 and PC-3 cells were transfected with miR-296 and antisense-miR-296, cell growth and apoptosis were then analyzed. Results The miR-296-5p expression was up-regulated by 2.22 folds in the CL-1 cells, which do not express significantly androgen receptor, than in LNCaP cells. Knockdown of miR-296-Sp induced apoptosis of CL-1 cells, but not LNCaP cells. However, knockdown of miR-296-Sp inhibited the growth rate of LNCaP cells cultured in absence of androgen. Conclusion MiR-296-5p could be irnportant for development of prostate cancer from androgen dependence to androgen independence.

  1. Accuracy of continuous noninvasive hemoglobin monitoring for the prediction of blood transfusions in trauma patients.

    Science.gov (United States)

    Galvagno, Samuel M; Hu, Peter; Yang, Shiming; Gao, Cheng; Hanna, David; Shackelford, Stacy; Mackenzie, Colin

    2015-12-01

    Early detection of hemorrhagic shock is required to facilitate prompt coordination of blood component therapy delivery to the bedside and to expedite performance of lifesaving interventions. Standard physical findings and vital signs are difficult to measure during the acute resuscitation stage, and these measures are often inaccurate until patients deteriorate to a state of decompensated shock. The aim of this study is to examine a severely injured trauma patient population to determine whether a noninvasive SpHb monitor can predict the need for urgent blood transfusion (universal donor or additional urgent blood transfusion) during the first 12 h of trauma patient resuscitation. We hypothesize that trends in continuous SpHb, combined with easily derived patient-specific factors, can identify the immediate need for transfusion in trauma patients. Subjects were enrolled if directly admitted to the trauma center, >17 years of age, and with a shock index (heart rate/systolic blood pressure) >0.62. Upon admission, a Masimo Radical-7 co-oximeter sensor (Masimo Corporation, Irvine, CA) was applied, providing measurement of continuous non-invasive hemoglobin (SpHb) levels. Blood was drawn and hemoglobin concentration analyzed and conventional pulse oximetry photopletysmograph signals were continuously recorded. Demographic information and both prehospital and admission vital signs were collected. The primary outcome was transfusion of at least one unit of packed red blood cells within 24 h of admission. Eight regression models (C1-C8) were evaluated for the prediction of blood use by comparing area under receiver operating curve (AUROC) at different time intervals after admission. 711 subjects had continuous vital signs waveforms available, to include heart rate (HR), SpHb and SpO2 trends. When SpHb was monitored for 15 min, SpHb did not increase AUROC for prediction of transfusion. The highest ROC was recorded for model C8 (age, sex, prehospital shock index, admission

  2. Regulatory T Cells Occupy an Isolated Niche in the Intestine that Is Antigen Independent

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    Lisa L. Korn

    2014-12-01

    Full Text Available Regulatory T cells (Tregs are CD4+ T cells that maintain immune homeostasis and prevent autoimmunity. Like all CD4+ T cells, Tregs require antigen-specific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII interactions for their development. However, the requirement for MHCII in Treg homeostasis in tissues such as intestinal lamina propria (LP is unknown. We examined LP Treg homeostasis in a transgenic mouse model that lacks peripheral TCR-MHCII interactions and generation of extrathymic Tregs (iTregs. Thymically generated Tregs entered the LP of weanlings and proliferated independently of MHCII to fill the compartment. The adult LP was a closed niche; new thymic Tregs were excluded, and Tregs in parabiotic pairs were LP resident. The isolated LP niche was interleukin-2 (IL-2 independent but dependent on commensal bacteria. Thus, an LP Treg niche can be filled, isolated, and maintained independently of antigen signals and iTregs. This niche may represent a tissue-specific mechanism for maintaining immune tolerance.

  3. Enhanced adhesion of osteoblastic cells on polystyrene films by independent control of surface topography and wettability

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Seung Yun [National Creative Research Center for Block Copolymer Self-Assembly, Departments of Environmental Science and Engineering and Chemical Engineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Kim, Eung-Sam [School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Jeon, Gumhye [National Creative Research Center for Block Copolymer Self-Assembly, Departments of Environmental Science and Engineering and Chemical Engineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Choi, Kwan Yong, E-mail: kchoi@postech.ac.kr [School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Kim, Jin Kon, E-mail: jkkim@postech.ac.kr [National Creative Research Center for Block Copolymer Self-Assembly, Departments of Environmental Science and Engineering and Chemical Engineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of)

    2013-04-01

    We independently controlled surface topography and wettability of polystyrene (PS) films by CF{sub 4} and oxygen plasma treatments, respectively, to evaluate the adhesion and proliferation of human fetal osteoblastic (hFOB) cells on the films. Among the CF{sub 4} plasma-treated PS films with the average surface roughness ranging from 0.9 to 70 nm, the highest adhesion of hFOB cells was observed on a PS film with roughness of ∼ 11 nm. When this film was additionally treated by oxygen plasma to provide a hydrophilic surface with a contact angle less than 10°, the proliferation of bone-forming cell was further enhanced. Thus, the plasma-based independent modification of PS film into an optimum nanotexture for human osteoblast cells could be appplied to materials used in bone tissue engineering. Highlights: ► New approach based on plasma treatment to independently control the surface topography and wettability ► The adhesion of human fetal osteoblast (hFOB) was enhanced on a surface with an average roughness of ∼ 11 nm. ► The adhesion and proliferation of hFOB was maximized when nanotextured surface became highly hydrophilic.

  4. Haemostatic function and biomarkers of endothelial damage before and after RBC transfusion in patients with haematologic disease

    DEFF Research Database (Denmark)

    Larsen, A M; Leinøe, E B; Johansson, P I;

    2015-01-01

    BACKGROUND AND OBJECTIVES: Transfusion of red blood cells (RBC) is beneficial for the patient but can also be harmful, as randomized trials have demonstrated increased infection rates, bleeding and mortality. The study aim was to investigate the response of the vascular system (the haemostatic...... function and the endothelium) to RBC transfusion. MATERIALS AND METHODS: Blood was sampled from patients with various transfusion-dependent haematologic diseases before 1 and 24 h after RBC transfusion. Primary and secondary haemostasis was evaluated by whole-blood impedance aggregometry (Multiplate...

  5. Genes involved in centrosome-independent mitotic spindle assembly in Drosophila S2 cells.

    Science.gov (United States)

    Moutinho-Pereira, Sara; Stuurman, Nico; Afonso, Olga; Hornsveld, Marten; Aguiar, Paulo; Goshima, Gohta; Vale, Ronald D; Maiato, Helder

    2013-12-01

    Animal mitotic spindle assembly relies on centrosome-dependent and centrosome-independent mechanisms, but their relative contributions remain unknown. Here, we investigated the molecular basis of the centrosome-independent spindle assembly pathway by performing a whole-genome RNAi screen in Drosophila S2 cells lacking functional centrosomes. This screen identified 197 genes involved in acentrosomal spindle assembly, eight of which had no previously described mitotic phenotypes and produced defective and/or short spindles. All 197 genes also produced RNAi phenotypes when centrosomes were present, indicating that none were entirely selective for the acentrosomal pathway. However, a subset of genes produced a selective defect in pole focusing when centrosomes were absent, suggesting that centrosomes compensate for this shape defect. Another subset of genes was specifically associated with the formation of multipolar spindles only when centrosomes were present. We further show that the chromosomal passenger complex orchestrates multiple centrosome-independent processes required for mitotic spindle assembly/maintenance. On the other hand, despite the formation of a chromosome-enriched RanGTP gradient, S2 cells depleted of RCC1, the guanine-nucleotide exchange factor for Ran on chromosomes, established functional bipolar spindles. Finally, we show that cells without functional centrosomes have a delay in chromosome congression and anaphase onset, which can be explained by the lack of polar ejection forces. Overall, these findings establish the constitutive nature of a centrosome-independent spindle assembly program and how this program is adapted to the presence/absence of centrosomes in animal somatic cells.

  6. Blood Transfusion Therapy in Patients with Heart Disease.

    Science.gov (United States)

    1982-04-07

    good health will not require the same transfusion therapy as patients with valvular heart disease who have congestive heart failure and...normal red cell volume and normal red cell oxygen transport function. 1 ,13 When the patient has valvular heart disease or myo- cardiopathy with...cardio- pulmonary bypass patients and in patients with severe valvular heart disease . Blood 1978;52:13-23. : 81. 197. Frledenberg WR, Myers WO, Plotka

  7. Spontaneous cancer-stromal cell fusion as a mechanism of prostate cancer androgen-independent progression.

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    Ruoxiang Wang

    Full Text Available We have previously shown that human prostate cancer cells are capable of acquiring malignant attributes through interaction with stromal cells in the tumor microenvironment, while the interacting stromal cells can also become affected with both phenotypic and genotypic alterations. This study used a co-culture model to investigate the mechanism underlying the co-evolution of cancer and stromal cells. Red fluorescent androgen-dependent LNCaP prostate cancer cells were cultured with a matched pair of normal and cancer-associated prostate myofibroblast cells to simulate cancer-stromal interaction, and cellular changes in the co-culture were documented by tracking the red fluorescence. We found frequent spontaneous fusions between cancer and stromal cells throughout the co-culture. In colony formation assays assessing the fate of the hybrid cells, most of the cancer-stromal fusion hybrids remained growth-arrested and eventually perished. However, some of the hybrids survived to form colonies from the co-culture with cancer-associated stromal cells. These derivative clones showed genomic alterations together with androgen-independent phenotype. The results from this study reveal that prostate cancer cells are fusogenic, and cancer-stromal interaction can lead to spontaneous fusion between the two cell types. While a cancer-stromal fusion strategy may allow the stromal compartment to annihilate invading cancer cells, certain cancer-stromal hybrids with increased survival capability may escape annihilation to form a derivative cancer cell population with an altered genotype and increased malignancy. Cancer-stromal fusion thus lays a foundation for an incessant co-evolution between cancer and the cancer-associated stromal cells in the tumor microenvironment.

  8. On How Fas Apoptosis-Independent Pathways Drive T Cell Hyperproliferation and Lymphadenopathy in lpr Mice.

    Science.gov (United States)

    Balomenos, Dimitrios; Shokri, Rahman; Daszkiewicz, Lidia; Vázquez-Mateo, Cristina; Martínez-A, Carlos

    2017-01-01

    Fas induces massive apoptosis in T cells after repeated in vitro T cell receptor (TCR) stimulation and is critical for lymphocyte homeostasis in Fas-deficient (lpr) mice. Although the in vitro Fas apoptotic mechanism has been defined, there is a large conceptual gap between this in vitro phenomenon and the pathway that leads to in vivo development of lymphadenopathy and autoimmunity. A striking abnormality in lpr mice is the excessive proliferation of CD4(+) and CD8(+) T cells, and more so of the double-negative TCR(+)CD4(-)CD8(-)B220(+) T cells. The basis of lpr T cell hyperproliferation remains elusive, as it cannot be explained by Fas-deficient apoptosis. T cell-directed p21 overexpression reduces hyperactivation/hyperproliferation of all lpr T cell subtypes and lymphadenopathy in lpr mice. p21 controls expansion of repeatedly stimulated T cells without affecting apoptosis. These results confirm a direct link between hyperactivation/hyperproliferation, autoreactivity, and lymphadenopathy in lpr mice and, with earlier studies, suggest that Fas apoptosis-independent pathways control lpr T cell hyperproliferation. lpr T cell hyperproliferation could be an indirect result of the defective apoptosis of repeatedly stimulated lpr T cells. Nonetheless, in this perspective, we argue for an alternative setting, in which lack of Fas would directly cause lpr T cell hyperactivation/hyperproliferation in vivo. We propose that Fas/Fas ligand (FasL) acts as an activation inhibitor of recurrently stimulated T cells, and that its disruption causes overexpansion of T cells in lpr mice. Research to define the underlying mechanism of this Fas/FasL effect could resolve the phenotype of lpr mice and lead to therapeutics for related human syndromes.

  9. Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas

    DEFF Research Database (Denmark)

    Dabrowska, Magdalena Julia; Dybkær, Karen; Johansen, Preben

    2009-01-01

    Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas; Pathogenic Potential Identified by Insertional Mutagenesis in a Murine T-Cell Lymphoma Model. Magdalena Julia Dabrowska *,1, Karen Dybkaer *,1, Preben Johansen *,2, Hans Erik Johnsen1 and Finn Skou Pedersen *,3 1 Department...... role in the development of MLV induced lymphomas and strongly indicates that retroviral insertional mutagenesis in murine models of human NHLs can be used to identify new genes involved in lymphomagenesis and, by use of functional assays, their impact on human lymphomas can be evaluated. Disclosures...

  10. Reporter cell activity within hydrogel constructs quantified from oxygen-independent bioluminescence.

    Science.gov (United States)

    Lambrechts, Dennis; Roeffaers, Maarten; Kerckhofs, Greet; Hofkens, Johan; Van de Putte, Tom; Schrooten, Jan; Van Oosterwyck, Hans

    2014-09-01

    By providing a three-dimensional (3D) support to cells, hydrogels offer a more relevant in vivo tissue-like environment as compared to two-dimensional cell cultures. Hydrogels can be applied as screening platforms to investigate in 3D the role of biochemical and biophysical cues on cell behaviour using bioluminescent reporter cells. Gradients in oxygen concentration that result from the interplay between molecular transport and cell metabolism can however cause substantial variability in the observed bioluminescent reporter cell activity. To assess the influence of these oxygen gradients on the emitted bioluminescence for various hydrogel geometries, a combined experimental and modelling approach was implemented. We show that the applied model is able to predict oxygen gradient independent bioluminescent intensities which correlate better to the experimentally determined viable cell numbers, as compared to the experimentally measured bioluminescent intensities. By analysis of the bioluminescence reaction dynamics we obtained a quantitative description of cellular oxygen metabolism within the hydrogel, which was validated by direct measurements of oxygen concentration within the hydrogel. Bioluminescence peak intensities can therefore be used as a quantitative measurement of reporter cell activity within a hydrogel, but an unambiguous interpretation of these intensities requires a compensation for the influence of cell-induced oxygen gradients on the luciferase activity.

  11. Blood transfusion after total shoulder arthroplasty: Which patients are at high risk?

    Directory of Open Access Journals (Sweden)

    Abdurrahman Kandil

    2016-01-01

    Full Text Available Purpose: There are multiple reported risk factors and a wide range of reported blood transfusion rates for total shoulder arthroplasty (TSA. There are no evidence-based guidelines for blood transfusions in TSA patients. Materials and Methods: We utilized the Nationwide Inpatient Sample to analyze 51,191 patients undergoing TSA between 1998 and 2011. The purpose was to describe the incidence and identify the preoperative factors that are independently associated with blood transfusion after TSA. In addition, we studied the association of blood transfusions with certain variables such as length of stay (LOS, total charges, and payer status. Results: The blood transfusion rate in our study was 6.1%. There was no difference in the rate of blood transfusions over the study period (P < 0.001. In our logistic regression model, significant associations were found with increased age (odds ratio [OR] =1.03, white race (OR = 1.05, higher Charlson-Deyo score (OR = 1.12, presence of ischemic heart disease (OR = 1.24, blood loss anemia (OR = 1.65, female gender (OR = 1.94, presence of coagulation disorders (OR = 2.25, and presence of deficiency anemia (OR = 3.5. Patients receiving a blood transfusion had higher total charges, a longer hospital LOS, and were more likely to be Medicare payers (P < 0.001. Conclusions: Our study found five clinically significant risk factors for blood transfusions for TSA: female gender, ischemic heart disease, deficiency anemia, coagulation disorder, and blood loss anemia. Patients with these risk factors should be considered higher risk for requiring a blood transfusion after TSA and counseled appropriately. Level of Evidence: Level II, retrospective cohort study, prognostic study.

  12. Low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome:a report of 2 cases%小剂量地西他滨联合异基因造血干细胞分次输注治疗老年骨髓增生异常综合征转急性髓性白血病2例报告

    Institute of Scientific and Technical Information of China (English)

    李云双; 陈永升; 聂伟业; 黄琴; 孔祥敬; 尹晓林

    2015-01-01

    Objective To explore the efficay of low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion( micro transplantation) for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome ( MDS-AML) .Methods Two patients diagnosed as MDS-AML were treated with chemotherapy regimen of low-dose decitabine or decitabine combined with CAG(cytosine arabinoside+aclacinomycin) and micro transplantation.The donors were children of patients with human leukocyte antigen semi-matched.Peripheral blood stem cells from the donors were mobilized with granulocyte colony-stimulating factor and then collected. Patients transfused PBSC about 36 hours after the chemotherapy finished.The disease status,platelet levels,survival timeand side effects were observed.Re sults Two cases did not achieve complete response.The survival times of Case 1 and Case 2 were 2 months and 4 months respectively. The platelet level in Case 1 increased remarkably after treatment,and reached to the maximal level of 59 ×109/L.No platelet transfusion was observed in Case 1.In Case 2,the interval of platelet transfusion was prolonged,and the patient was gradually independent on platelet transfusions. No graft-versus-host disease occurred in the two patients.Conclusion For elderly patients with MDS-AML,low-dose decitabine combined with micro transplantation can not cure the disease,but can prolong the survival time,increase the level of platelet and improve the quality of life.%目的 观察小剂量地西他滨联合异基因造血干细胞分次输注(微移植)治疗老年骨髓增生异常综合征转急性髓性白血病( MDS-AML)的疗效. 方法 对2例确诊为MDS-AML患者分别予小剂量地西他滨或地西他滨联合CAG方案(阿糖胞苷+阿克拉霉素)化疗加微移植治疗,供者为人类白细胞抗原半相合的患者子女,采集重组人粒细胞集落刺激因子动员后的供者外周血

  13. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

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    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  14. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    Energy Technology Data Exchange (ETDEWEB)

    Horita, Nobukatsu [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Tsuchiya, Kiichiro, E-mail: kii.gast@tmd.ac.jp [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Hayashi, Ryohei [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Department of Gastroenterology and Metabolism, Hiroshima University (Japan); Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Okamoto, Ryuichi; Nakamura, Tetsuya [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan)

    2014-11-28

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus.

  15. Clinical Response and Transfusion Reactions of Sheep Subjected to Single Homologous Blood Transfusion

    Directory of Open Access Journals (Sweden)

    Rejane Santos Sousa

    2014-01-01

    Full Text Available Studies in relation to blood conservation and responses to transfusion are scarce for ruminants. We evaluated the clinical manifestations of sheep that received a single homologous transfusion of whole blood, focusing on transfusion reactions. Eighteen adult sheep were subjected to a single phlebotomy to withdraw 40% of the total blood volume, which was placed into CPDA-1 bags and then divided into G0, animals that received fresh blood, and G15 and G35, animals that received blood stored for 15 or 35 days, respectively. Clinical observations were recorded throughout the transfusion, whereas heart rate, respiratory rate, and rectal temperature were assessed at the following times: 24 hours after phlebotomy and before transfusion; 30 minutes, six, twelve, 24, 48, 72, and 96 hours and eight and 16 days after transfusion. All groups presented transfusion reactions, among which hyperthermia was the most frequent (50% of animals. Tachycardia occurred most frequently in the G35 animals (50% of them. During transfusion G35 animals presented more clinical manifestation (P<0.05. Transfusion of fresh or stored total blood improved the blood volume, but transfusion reactions occurred, demonstrating that a single transfusion of fresh or stored blood can cause inflammatory and febrile nonhemolytic transfusion reactions in sheep.

  16. TNF-α Contributes to Caspase-3 Independent Apoptosis in Neuroblastoma Cells: Role of NFAT

    Science.gov (United States)

    Álvarez, Susana; Blanco, Almudena; Fresno, Manuel; Muñoz-Fernández, Ma Ángeles

    2011-01-01

    There is increasing evidence that soluble factors in inflammatory central nervous system diseases not only regulate the inflammatory process but also directly influence electrophysiological membrane properties of neurons and astrocytes. In this context, the cytokine TNF-α (tumor necrosis factor-α) has complex injury promoting, as well as protective, effects on neuronal viability. Up-regulated TNF-α expression has also been found in various neurodegenerative diseases such as cerebral malaria, AIDS dementia, Alzheimer's disease, multiple sclerosis, and stroke, suggesting a potential pathogenic role of TNF-α in these diseases as well. We used the neuroblastoma cells SK-N-MC. Transcriptional activity was measured using luciferase reporter gene assays by using lipofectin. We performed cotransfection experiments of NFAT (nuclear factor of activated T cells) promoter constructed with a dominant negative version of NFAT (dn-NFAT). Cell death was performed by MTT (3-(4,5-dimethylthiazol-2-yl)5,5-diphenyltetrazolium bromide) and TUNEL assays. NFAT translocation was confirmed by Western blot. Involvement of NFAT in cell death was assessed by using VIVIT. P53, Fas-L, caspase-3, and caspase-9 expressions were carried out by Western blot. The mechanisms involved in TNF-α-induced cell death were assessed by using microarray analysis. TNF-α causes neuronal cell death in the absence of glia. TNF-α treatment results in nuclear translocation of NFAT through activation of calcineurin in a Ca2+ independent manner. We demonstrated the involvement of FasL/Fas, cytochrome c, and caspase-9 but the lack of caspase-3 activation. NB cell death was absolutely reverted in the presence of VIVIT, and partially diminished by anti-Fas treatment. These data demonstrate that TNF-α promotes FasL expression through NFAT activation in neuroblastoma cells and this event leads to increased apoptosis through independent caspase-3 activation. PMID:21298033

  17. Jak2-Independent Activation of Stat3 by Intracellular Angiotensin II in Human Mesangial Cells

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    Rekha Singh

    2011-01-01

    Full Text Available Ang II is shown to mediate the stimulatory effect of high glucose on TGF-b1 and extracellular matrix proteins in glomerular mesangial cells. Also inhibition of Ang II formation in cell media (extracellular and lysates (intracellular blocks high-glucose effects on TGF-b1 and matrix more effectively compared to inhibition of extracellular Ang II alone. To investigate whether intracellular Ang II can stimulate TGF-b1 and matrix independent of extracellular Ang II, cultured human mesangial cells were transfected with Ang II to increase intracellular Ang II levels and its effects on TGF-b1 and matrix proteins were determined. Prior to transfection, cells were treated with candesartan to block extracellular Ang II-induced responses via cell membrane AT1 receptors. Transfection of cells with Ang II resulted in increased levels of intracellular Ang II which was accompanied by increased production of TGF-b1, collagen IV, fibronectin, and cell proliferation as well. On further examination, intracellular Ang II was found to activate Stat3 transcription factor including increased Stat3 protein expression, tyrosine 705 phosphorylation, and DNA-binding activity. Treatment with AG-490, an inhibitor of Jak2, did not block intracellular Ang II-induced Stat3 phosphorylation at tyrosine 705 residue indicating a Jak2-independent mechanism used by intracellular Ang II for Stat3 phosphorylation. In contrast, extracellular Ang II-induced tyrosine 705 phosphorylation of Stat3 was inhibited by AG-490 confirming the presence of a Jak2-dependent pathway. These findings suggest that intracellular Ang II increases TGF-b1 and matrix in human mesangial cells and also activates Stat3 transcription factor without involvement of the extracellular Ang II signaling pathway.

  18. Potassium changes associated with blood transfusion in pediatric patients.

    Science.gov (United States)

    Olson, Jordan; Talekar, Mala; Sachdev, Mansi; Castellani, William; De la Cruz, Nestor; Davis, Jerry; Liao, Jason; George, Melissa

    2013-06-01

    Storing packed red blood cells (pRBCs) increases the potassium concentration. This effect is characterized in citrate phosphate dextrose/citrate phosphate dextrose adenine units but not published for Adsol (AS-5) units. The change in whole-blood potassium concentration in pediatric patients during routine transfusion is also poorly characterized. In this study, pediatric patients undergoing transfusion had pre- and posttransfusion whole-blood potassium measurements. The pRBC unit transfused and the unit's segment were sampled, with potassium concentration measured. In addition, potassium concentration in AS-5 units was measured over 42 days of storage. Unit extracellular potassium increased in AS-5 units after day 7 at 0.83 mmol/L/d. The mean change in patient potassium concentration was 0.08 mmol/L (range, -0.5 to 0.5 mmol/L). No correlation with unit age or unit potassium concentration was identified with change in patient whole-blood potassium concentration. The lack of clinical effect on patient potassium does not support the use of "fresh" pRBC units with routine pediatric transfusion.

  19. Exchange transfusion in complicated pediatric malaria: A critical appraisal.

    Science.gov (United States)

    Barman, Himesh

    2015-04-01

    Complicated falciparum malaria is a killer disease resulting in high mortality in spite of appropriate treatment. Some workers have reported improved survival when adjunct exchange blood transfusion is included in the treatment modality while others opine against it. This review is an effort to address and critically appraise current evidence for the treatment mode for severe malaria. The literature was searched with a specified search strategy to identify reports of children who underwent exchange transfusion for severe malaria. Total 23 children who underwent exchange transfusion for severe falciparum malaria published by 9 authors were identified. Age ranged from 5 months to 16 years with a mean age of 6.4 years. The average preprocedure parasite index (PI) was 41.4% (95confidence interval [CI]; 31.2-51.4). The average blood volume exchanged was 118.6% (95% CI; 94.7-143) of the circulating blood volume. The average postexchange reduction in PI was 34.1% (95% CI; 25.4-42.8). Three out of 23 children encountered some complications. All the children survivedKeywords: Exchange blood transfusion, parasite index, pediatric Intensive Care Unit, red cell exchange, severe falciparum malaria.

  20. Exchange transfusion in complicated pediatric malaria: A critical appraisal

    Directory of Open Access Journals (Sweden)

    Himesh Barman

    2015-01-01

    Full Text Available Complicated falciparum malaria is a killer disease resulting in high mortality in spite of appropriate treatment. Some workers have reported improved survival when adjunct exchange blood transfusion is included in the treatment modality while others opine against it. This review is an effort to address and critically appraise current evidence for the treatment mode for severe malaria. The literature was searched with a specified search strategy to identify reports of children who underwent exchange transfusion for severe malaria. Total 23 children who underwent exchange transfusion for severe falciparum malaria published by 9 authors were identified. Age ranged from 5 months to 16 years with a mean age of 6.4 years. The average preprocedure parasite index (PI was 41.4% (95confidence interval [CI]; 31.2-51.4. The average blood volume exchanged was 118.6% (95% CI; 94.7-143 of the circulating blood volume. The average postexchange reduction in PI was 34.1% (95% CI; 25.4-42.8. Three out of 23 children encountered some complications. All the children survivedKeywords: Exchange blood transfusion, parasite index, pediatric Intensive Care Unit, red cell exchange, severe falciparum malaria.

  1. B-cell-independent lymphoid tissue infection by a B-cell-tropic rhadinovirus.

    Science.gov (United States)

    Chao, Brittany; Frederico, Bruno; Stevenson, Philip G

    2015-09-01

    Lymphocytes provide gammaherpesviruses with a self-renewing substrate for persistent infection and with transport to mucosal sites for host exit. Their role in the initial colonization of new hosts is less clear. Murid herpesvirus 4 (MuHV-4), an experimentally accessible, B-cell-tropic rhadinovirus (gamma-2 herpesvirus), persistently infects both immunocompetent and B-cell-deficient mice. A lack of B-cells did not compromise MuHV-4 entry into lymphoid tissue, which involved myeloid cell infection. However, it impaired infection amplification and MuHV-4 exit from lymphoid tissue, which involved myeloid to B-cell transfer.

  2. Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells.

    NARCIS (Netherlands)

    Broker, L.E.; Huisman, C.; Span, SW; Rodriguez, J.A.; Kruyt, F.A.E.; Giaccone, G.

    2004-01-01

    We have previously reported that the microtubule stabilizing agents (MSAs) paclitaxel, epothilone B and discodermolide induce caspase-independent cell death in non-small cell lung cancer (NSCLC) cells. Here we present two lines of evidence indicating a central role for the lysosomal protease catheps

  3. Downregulation of Akt1 Inhibits Anchorage-Independent Cell Growth and Induces Apoptosis in Cancer Cells

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    Xuesong Liu

    2001-01-01

    Full Text Available The serine/threonine kinases, Akti/PKBα, Akt2/PKBβ, and Akt3/PKBγ, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an AM antisense oligonucleotide (AS to specifically downregulate Akti protein in both cancer and normal cells. Our data indicate that AM AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FRCS analysis and a caspase activity assay. Conversely, Akti AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF, fibroblast from muscle (FBM, and mammary gland epithelial 184135 cells. In addition, AM AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akti is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of AM may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.

  4. Storage time of transfused blood and disease recurrence after colorectal cancer surgery

    DEFF Research Database (Denmark)

    Mynster, T; Nielsen, Hans Jørgen

    2001-01-01

    BACKGROUND: Perioperative blood transfusion and subsequent development of postoperative infectious complications may lead to poor prognosis of patients with colorectal cancer. It has been suggested that the development of postoperative infectious complications may be related to the storage time...... of the transfused blood. Therefore, we studied the relationship between blood storage time and the development of disease recurrence and long-term survival after colorectal cancer surgery. METHODS: Preoperative and postoperative data were prospectively recorded in 740 patients undergoing elective resection...... complications. CONCLUSION: Transfusion of buffy-coat-depleted red cells suspended in saline, adenine, glucose, and mannitol blood stored for cancer surgery....

  5. Storage time of transfused blood and disease recurrence after colorectal cancer surgery

    DEFF Research Database (Denmark)

    Mynster, T; Nielsen, Hans Jørgen

    2001-01-01

    of the transfused blood. Therefore, we studied the relationship between blood storage time and the development of disease recurrence and long-term survival after colorectal cancer surgery. METHODS: Preoperative and postoperative data were prospectively recorded in 740 patients undergoing elective resection...... complications. CONCLUSION: Transfusion of buffy-coat-depleted red cells suspended in saline, adenine, glucose, and mannitol blood stored for cancer surgery.......BACKGROUND: Perioperative blood transfusion and subsequent development of postoperative infectious complications may lead to poor prognosis of patients with colorectal cancer. It has been suggested that the development of postoperative infectious complications may be related to the storage time...

  6. cGMP-independent nitric oxide signaling and regulation of the cell cycle

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    Cintron Ana

    2005-11-01

    Full Text Available Abstract Background Regulatory functions of nitric oxide (NO• that bypass the second messenger cGMP are incompletely understood. Here, cGMP-independent effects of NO• on gene expression were globally examined in U937 cells, a human monoblastoid line that constitutively lacks soluble guanylate cyclase. Differentiated U937 cells (>80% in G0/G1 were exposed to S-nitrosoglutathione, a NO• donor, or glutathione alone (control for 6 h without or with dibutyryl-cAMP (Bt2cAMP, and then harvested to extract total RNA for microarray analysis. Bt2cAMP was used to block signaling attributable to NO•-induced decreases in cAMP. Results NO• regulated 110 transcripts that annotated disproportionately to the cell cycle and cell proliferation (47/110, 43% and more frequently than expected contained AU-rich, post-transcriptional regulatory elements (ARE. Bt2cAMP regulated 106 genes; cell cycle gene enrichment did not reach significance. Like NO•, Bt2cAMP was associated with ARE-containing transcripts. A comparison of NO• and Bt2cAMP effects showed that NO• regulation of cell cycle genes was independent of its ability to interfere with cAMP signaling. Cell cycle genes induced by NO• annotated to G1/S (7/8 and included E2F1 and p21/Waf1/Cip1; 6 of these 7 were E2F target genes involved in G1/S transition. Repressed genes were G2/M associated (24/27; 8 of 27 were known targets of p21. E2F1 mRNA and protein were increased by NO•, as was E2F1 binding to E2F promoter elements. NO• activated p38 MAPK, stabilizing p21 mRNA (an ARE-containing transcript and increasing p21 protein; this increased protein binding to CDE/CHR promoter sites of p21 target genes, repressing key G2/M phase genes, and increasing the proportion of cells in G2/M. Conclusion NO• coordinates a highly integrated program of cell cycle arrest that regulates a large number of genes, but does not require signaling through cGMP. In humans, antiproliferative effects of NO• may rely

  7. Plasma and Plasma Protein Product Transfusion: A Canadian Blood Services Centre for Innovation Symposium.

    Science.gov (United States)

    Zeller, Michelle P; Al-Habsi, Khalid S; Golder, Mia; Walsh, Geraldine M; Sheffield, William P

    2015-07-01

    Plasma obtained via whole blood donation processing or via apheresis technology can either be transfused directly to patients or pooled and fractionated into plasma protein products that are concentrates of 1 or more purified plasma protein. The evidence base supporting clinical efficacy in most of the indications for which plasma is transfused is weak, whereas high-quality evidence supports the efficacy of plasma protein products in at least some of the clinical settings in which they are used. Transfusable plasma utilization remains composed in part of applications that fall outside of clinical practice guidelines. Plasma contains all of the soluble coagulation factors and is frequently transfused in efforts to restore or reinforce patient hemostasis. The biochemical complexities of coagulation have in recent years been rationalized in newer cell-based models that supplement the cascade hypothesis. Efforts to normalize widely used clinical hemostasis screening test values by plasma transfusion are thought to be misplaced, but superior rapid tests have been slow to emerge. The advent of non-vitamin K-dependent oral anticoagulants has brought new challenges to clinical laboratories in plasma testing and to clinicians needing to reverse non-vitamin K-dependent oral anticoagulants urgently. Current plasma-related controversies include prophylactic plasma transfusion before invasive procedures, plasma vs prothrombin complex concentrates for urgent warfarin reversal, and the utility of increased ratios of plasma to red blood cell units transfused in massive transfusion protocols. The first recombinant plasma protein products to reach the clinic were recombinant hemophilia treatment products, and these donor-free equivalents to factors VIII and IX are now being supplemented with novel products whose circulatory half-lives have been increased by chemical modification or genetic fusion. Achieving optimal plasma utilization is an ongoing challenge in the interconnected

  8. Transfusion of blood during cardiac surgery is associated with higher long-term mortality in low-risk patients

    DEFF Research Database (Denmark)

    Jakobsen, Carl-Johan; Ryhammer, Pia Katarina; Jensen, Mariann Tang

    2012-01-01

    Numerous reports have emphasized the need for reduction in transfusions of allogeneic red blood cells (RBC) due to increased morbidity and mortality. Nevertheless, transfusion rates are still high in several cardiac surgery institutions. Reports on long-term survival after cardiac surgery and RBC...

  9. Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells.

    Directory of Open Access Journals (Sweden)

    Hui-Hua Li

    Full Text Available Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC and pulmonary artery (RPAEC endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1 in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC from wild type and cav-1(-/- mice and noted that ~ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF, persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1(-/- mice was through caveolae-independent pathway(s including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization] consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1(-/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process.

  10. Computational Analysis of Transcriptional Circuitries in Human Embryonic Stem Cells Reveals Multiple and Independent Networks

    Directory of Open Access Journals (Sweden)

    Xiaosheng Wang

    2014-01-01

    Full Text Available It has been known that three core transcription factors (TFs, NANOG, OCT4, and SOX2, collaborate to form a transcriptional circuitry to regulate pluripotency and self-renewal of human embryonic stem (ES cells. Similarly, MYC also plays an important role in regulating pluripotency and self-renewal of human ES cells. However, the precise mechanism by which the transcriptional regulatory networks control the activity of ES cells remains unclear. In this study, we reanalyzed an extended core network, which includes the set of genes that are cobound by the three core TFs and additional TFs that also bind to these cobound genes. Our results show that beyond the core transcriptional network, additional transcriptional networks are potentially important in the regulation of the fate of human ES cells. Several gene families that encode TFs play a key role in the transcriptional circuitry of ES cells. We also demonstrate that MYC acts independently of the core module in the regulation of the fate of human ES cells, consistent with the established argument. We find that TP53 is a key connecting molecule between the core-centered and MYC-centered modules. This study provides additional insights into the underlying regulatory mechanisms involved in the fate determination of human ES cells.

  11. NOPO modulates Egr-induced JNK-independent cell death in Drosophila

    Institute of Scientific and Technical Information of China (English)

    Xianjue Ma; Jiuhong Huang; Lixia Yang; Yang Yang; Wenzhe Li; Lei Xue

    2012-01-01

    Tumor necrosis factor (TNF) family ligands play essential roles in regulating a variety of cellular processes including proliferation,differentiation and survival.Expression of Drosophila TNF ortholog Eiger (Egr) induces JNK-dependent cell death,while the roles of caspases in this process remain elusive.To further delineate the Egr-triggered cell death pathway,we performed a genetic screen to identify dominant modifiers of the Egr-induced cell death phenotype.Here we report that Egr elicits a caspase-mediated cell death pathway independent of JNK signaling.Furthermore,we show NOPO,the Drosophila ortholog of TRIP (TRAF interacting protein) encoding an E3 ubiquitin ligase,modulates Egr-induced Caspase-mediated cell death through transcriptional activation of pro-apoptotic genes reaper and hid.Finally,we found Bendless and dUEV1a,an ubiquitin-conjugating E2 enzyme complex,regulates NOPO-triggered cell death.Our results indicate that the Ben-dUEV1a complex constitutes a molecular switch that bifurcates the Egr-induced cell death signaling into two pathways mediated by JNK and caspases respectively.

  12. Translation-independent circadian control of the cell cycle in a unicellular photosynthetic eukaryote.

    Science.gov (United States)

    Miyagishima, Shin-ya; Fujiwara, Takayuki; Sumiya, Nobuko; Hirooka, Shunsuke; Nakano, Akihiko; Kabeya, Yukihiro; Nakamura, Mami

    2014-05-08

    Circadian rhythms of cell division have been observed in several lineages of eukaryotes, especially photosynthetic unicellular eukaryotes. However, the mechanism underlying the circadian regulation of the cell cycle and the nature of the advantage conferred remain unknown. Here, using the unicellular red alga Cyanidioschyzon merolae, we show that the G1/S regulator RBR-E2F-DP complex links the G1/S transition to circadian rhythms. Time-dependent E2F phosphorylation promotes the G1/S transition during subjective night and this phosphorylation event occurs independently of cell cycle progression, even under continuous dark or when cytosolic translation is inhibited. Constitutive expression of a phospho-mimic of E2F or depletion of RBR unlinks cell cycle progression from circadian rhythms. These transgenic lines are exposed to higher oxidative stress than the wild type. Circadian inhibition of cell cycle progression during the daytime by RBR-E2F-DP pathway likely protects cells from photosynthetic oxidative stress by temporally compartmentalizing photosynthesis and cell cycle progression.

  13. Role of Ca2+-independent phospholipase A2 in cell growth and signaling.

    Science.gov (United States)

    Hooks, Shelley B; Cummings, Brian S

    2008-10-30

    Phospholipase A(2) (PLA(2)) are esterases that cleave glycerophospholipids to release fatty acids and lysophospholipids. Several studies demonstrate that PLA(2) regulate growth and signaling in several cell types. However, few of these studies have focused on Ca2+-independent phospholipase A(2) (iPLA(2) or Group VI PLA(2)). This class of PLA(2) was originally suggested to mediate phospholipid remodeling in several cell types including macrophages. As such, it was labeled as a housekeeping protein and thought not to play as significant of roles in cell growth as its older counterparts cytosolic PLA(2) (cPLA(2) or Group IV PLA(2)) and secretory PLA(2) (sPLA(2) or Groups I-III, V and IX-XIV PLA(2)). However, several recent studies demonstrate that iPLA(2) mediate cell growth, and do so by participating in signal transduction pathways that include epidermal growth factor receptors (EGFR), mitogen activated protein kinases (MAPK), mdm2, and even the tumor suppressor protein p53 and the cell cycle regulator p21. The exact mechanism by which iPLA(2) mediates these pathways are not known, but likely involve the generation of lipid signals such as arachidonic acid, lysophosphatidic acid (LPA) and lysophosphocholines (LPC). This review discusses the role of iPLA(2) in cell growth with special emphasis placed on their role in cell signaling. The putative lipid signals involved are also discussed.

  14. Transcription-independent function of Polycomb group protein PSC in cell cycle control.

    Science.gov (United States)

    Mohd-Sarip, Adone; Lagarou, Anna; Doyen, Cecile M; van der Knaap, Jan A; Aslan, Ülkü; Bezstarosti, Karel; Yassin, Yasmin; Brock, Hugh W; Demmers, Jeroen A A; Verrijzer, C Peter

    2012-05-11

    Polycomb group (PcG) proteins control development and cell proliferation through chromatin-mediated transcriptional repression. We describe a transcription-independent function for PcG protein Posterior sex combs (PSC) in regulating the destruction of cyclin B (CYC-B). A substantial portion of PSC was found outside canonical PcG complexes, instead associated with CYC-B and the anaphase-promoting complex (APC). Cell-based experiments and reconstituted reactions established that PSC and Lemming (LMG, also called APC11) associate and ubiquitylate CYC-B cooperatively, marking it for proteosomal degradation. Thus, PSC appears to mediate both developmental gene silencing and posttranslational control of mitosis. Direct regulation of cell cycle progression might be a crucial part of the PcG system's function in development and cancer.

  15. Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation.

    Science.gov (United States)

    Jia, Ting; Anandhan, Annandurai; Massilamany, Chandirasegaran; Rajasekaran, Rajkumar A; Franco, Rodrigo; Reddy, Jay

    2015-12-01

    Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139-151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT induced cell death in antigen-specific, autoreactive T cells, but the effects were not selective, because both proliferating and non-proliferating cells were equally affected independent of antigenic stimulation. Furthermore, DHT-exposed PLP 139-151-specific T cells did not show any shift in cytokine production; rather, frequencies of cytokine-producing PLP-specific T cells were significantly reduced, irrespective of T helper (Th) 1, Th2, and Th17 subsets of cytokines. By evaluating cell death and autophagy pathways, we provide evidence for the induction of autophagy to be associated with cell death caused by DHT. Taken together, the data provide new insights into the role of DHT and indicate that cell death and autophagy contribute to the therapeutic effects of androgens in autoreactive T cells.

  16. Dnd knockout ablates germ cells and demonstrates germ cell independent sex differentiation in Atlantic salmon

    NARCIS (Netherlands)

    Wargelius, Anna; Leininger, Sven; Skaftnesmo, Kai Ove; Kleppe, Lene; Andersson, Eva; Taranger, Geir Lasse; Schulz, Rüdiger W; Edvardsen, Rolf B

    2016-01-01

    Introgression of farmed salmon escapees into wild stocks is a major threat to the genetic integrity of wild populations. Using germ cell-free fish in aquaculture may mitigate this problem. Our study investigated whether it is possible to produce germ cell-free salmon in F0 by using CRISPR-Cas9 to kn

  17. Transfusion Associated Hyperkalemia and Cardiac Arrest in an Infant after Extracorporeal Membrane Oxygenation

    Directory of Open Access Journals (Sweden)

    Do Wan Kim

    2015-05-01

    Full Text Available Cardiac arrest associated with hyperkalemia during red blood cell transfusion is a rare but fatal complication. Herein, we report a case of transfusion-associated cardiac arrest following the initiation of extracorporeal membrane oxygenation support in a 9-month old infant. Her serum potassium level was increased to 9.0 mEq/L, soon after the newly primed circuit with pre-stored red blood cell (RBC was started and followed by sudden cardiac arrest. Eventually, circulation was restored and the potassium level decreased to 5.1 mEq/L after 5 min. Extracorporeal membrane oxygenation (ECMO priming is a relatively massive transfusion into a pediatric patient. Thus, to prevent cardiac arrest during blood-primed ECMO in neonates and infants, freshly irradiated and washed RBCs should be used when priming the ECMO circuit, to minimize the potassium concentration. Also, physicians should be aware of all possible complications associated with transfusions during ECMO.

  18. Mass casualty events: blood transfusion emergency preparedness across the continuum of care.

    Science.gov (United States)

    Doughty, Heidi; Glasgow, Simon; Kristoffersen, Einar

    2016-04-01

    Transfusion support is a key enabler to the response to mass casualty events (MCEs). Transfusion demand and capability planning should be an integrated part of the medical planning process for emergency system preparedness. Historical reviews have recently supported demand planning for MCEs and mass gatherings; however, computer modeling offers greater insights for resource management. The challenge remains balancing demand and supply especially the demand for universal components such as group O red blood cells. The current prehospital and hospital capability has benefited from investment in the management of massive hemorrhage. The management of massive hemorrhage should address both hemorrhage control and hemostatic support. Labile blood components cannot be stockpiled and a large surge in demand is a challenge for transfusion providers. The use of blood components may need to be triaged and demand managed. Two contrasting models of transfusion planning for MCEs are described. Both illustrate an integrated approach to preparedness where blood transfusion services work closely with health care providers and the donor community. Preparedness includes appropriate stock management and resupply from other centers. However, the introduction of alternative transfusion products, transfusion triage, and the greater use of an emergency donor panel to provide whole blood may permit greater resilience.

  19. One size will never fit all: the future of research in pediatric transfusion medicine.

    Science.gov (United States)

    Josephson, Cassandra D; Mondoro, Traci Heath; Ambruso, Daniel R; Sanchez, Rosa; Sloan, Steven R; Luban, Naomi L C; Widness, John A

    2014-11-01

    There is concern at the National Heart, Lung, and Blood Institute (NHLBI) and among transfusion medicine specialists regarding the small number of investigators and studies in the field of pediatric transfusion medicine (PTM). Accordingly, the objective of this article is to provide a snapshot of the clinical and translational PTM research considered to be of high priority by pediatricians, neonatologists, and transfusion medicine specialists. Included is a targeted review of three research areas of importance: (i) transfusion strategies, (ii) short- and long-term clinical consequences, and (iii) transfusion-transmitted infectious diseases. The recommendations by PTM and transfusion medicine specialists represent opportunities and innovative strategies to execute translational research, observational studies, and clinical trials of high relevance to PTM. With the explosion of new biomedical knowledge and increasingly sophisticated methodologies over the past decade, this is an exciting time to consider transfusion medicine as a paradigm for addressing questions related to fields such as cell biology, immunology, neurodevelopment, outcomes research, and many others. Increased awareness of PTM as an important, fertile field and the promotion of accompanying opportunities will help establish PTM as a viable career option and advance basic and clinical investigation to improve the health and wellbeing of children.

  20. Both canonical and non-canonical Wnt signaling independently promote stem cell growth in mammospheres.

    Directory of Open Access Journals (Sweden)

    Alexander M Many

    Full Text Available The characterization of mammary stem cells, and signals that regulate their behavior, is of central importance in understanding developmental changes in the mammary gland and possibly for targeting stem-like cells in breast cancer. The canonical Wnt/β-catenin pathway is a signaling mechanism associated with maintenance of self-renewing stem cells in many tissues, including mammary epithelium, and can be oncogenic when deregulated. Wnt1 and Wnt3a are examples of ligands that activate the canonical pathway. Other Wnt ligands, such as Wnt5a, typically signal via non-canonical, β-catenin-independent, pathways that in some cases can antagonize canonical signaling. Since the role of non-canonical Wnt signaling in stem cell regulation is not well characterized, we set out to investigate this using mammosphere formation assays that reflect and quantify stem cell properties. Ex vivo mammosphere cultures were established from both wild-type and Wnt1 transgenic mice and were analyzed in response to manipulation of both canonical and non-canonical Wnt signaling. An increased level of mammosphere formation was observed in cultures derived from MMTV-Wnt1 versus wild-type animals, and this was blocked by treatment with Dkk1, a selective inhibitor of canonical Wnt signaling. Consistent with this, we found that a single dose of recombinant Wnt3a was sufficient to increase mammosphere formation in wild-type cultures. Surprisingly, we found that Wnt5a also increased mammosphere formation in these assays. We confirmed that this was not caused by an increase in canonical Wnt/β-catenin signaling but was instead mediated by non-canonical Wnt signals requiring the receptor tyrosine kinase Ror2 and activity of the Jun N-terminal kinase, JNK. We conclude that both canonical and non-canonical Wnt signals have positive effects promoting stem cell activity in mammosphere assays and that they do so via independent signaling mechanisms.

  1. DNA methylation-independent reversion of gemcitabine resistance by hydralazine in cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria

    Full Text Available BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase.

  2. An attempt to induce transient immunosuppression pre-erythrocytapheresis in a girl with sickle cell disease, a history of severe delayed hemolytic transfusion reactions and need for hip prosthesis

    Directory of Open Access Journals (Sweden)

    Alessandro Cattoni

    2013-06-01

    Full Text Available We report on a case of delayed hemolytic transfusion reaction (DHTR occurred 7 days after an erythrocytapheresis or eritroexchange procedure (EEX treated with rituximab and glucocorticoids in a 15-years old patient with sickle cell disease. EEX was performed despite a previous diagnosis of alloimmunization, in order to reduce hemoglobin S rate before a major surgery for avascular necrosis of the femoral head. A first dose of rituximab was administered before EEX. However, rituximab couldn’t prevent DHTR that occurred with acute hemolysis, hemoglobinuria and hyper-bilirubinemia. A further dose of rituximab and three boli of methylprednisolone were given after the onset of the reaction. It is likely that the combined use of rituximab and steroids managed to gradually improve both patient’s general conditions and hemoglobin levels. Nor early or late side effects were registered in a 33-months follow-up period. This report suggests the potential effectiveness and safety of rituximab in combination with steroids in managing and mitigating the symptoms of delayed post-transfusional hemolytic reactions in alloimmunized patients affected by sickle cell disease with absolute need for erythrocytapheresis.

  3. [Blood transfusion: the challenges for tomorrow?].

    Science.gov (United States)

    Folléa, Gilles; Garraud, Olivier; Tiberghien, Pierre

    2015-02-01

    As any therapeutic means, blood transfusion requires regular evaluation, particularly for its indications, effectiveness and risks. The availability of randomized clinical trials, the evolution of the quality of blood components, and the economic constraints shared by all countries, all lead to rethink both transfusion therapy as a whole and the organization of the transfusion chain from donor to recipient. The main tools available to improve transfusion and the transfusion chain management are the following: programs of patient blood management (PBM) to optimize the use of blood products with a patient centred approach, blood supply management tools to improve the effectiveness and efficiency of the transfusion chain, donor management tools to adapt donor collections to the patients' needs in compliance with safety requirements for patients and donors, and coordination of these activities. A better understanding of these tools and their implementation will certainly be major challenges for transfusion medicine in the near future. Integrating these evolutions in regulations through the revision of the European Directives on blood and blood components (the review process is expected to be launched in 2015) should enroll them in the long term, for the benefit of patients, donors and all other stakeholders involved in the transfusion chain.

  4. Transfusion medicine in obstetrics and gynecology.

    Science.gov (United States)

    Santoso, J T; Lin, D W; Miller, D S

    1995-06-01

    Obstetricians and Gynecologists care for many patients with conditions potentially requiring blood transfusions. Cesarean section and hysterectomy are the two surgeries performed most frequently and both have the potential for blood loss requiring transfusion. Other examples include postpartum hemorrhage, placenta previa, and ruptured ectopic pregnancy. Obstetricians and gynecologists need to become knowledgeable about the ever-changing aspects of blood transfusion and apply it in their clinical practice. This review intends to update obstetricians and gynecologists and other health care professionals about the basic as well as the latest technologies of blood transfusion. The different types of blood components are discussed including their preparation, indications, risks, and benefits. The complications of blood transfusion and their management are reviewed, including infections, noninfectious, and immunological etiologies. HIV and hepatitis are explored, these being the most serious infectious risks of transfusion. Autologous blood transfusion, an underutilized option, is examined. Hemodilution and intraoperative blood salvage, other techniques for using the patient's own blood, are discussed. Finally, synthetic agents such as erythropoietin, granulocyte colony-stimulating factors, factors, desmopressin acetate, gonadotropin-releasing hormone agonists, and new products are introduced as potential replacements to blood transfusion in the future.

  5. Evidence Based Studies in Clinical Transfusion Medicine

    NARCIS (Netherlands)

    A.J.G. Jansen (Gerard)

    2007-01-01

    textabstractAfter the introduction of blood component therapy in the 1960s, more and more attention is given to clinical transfusion medicine. Although blood transfusion is an important treatment in different clinical settings, there are still lack of much randomized clinical trials. Nowadays bloo

  6. Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells.

    Science.gov (United States)

    Li, Xiang; Zhao, Shu-Juan; Shi, Hai-Lian; Qiu, Shui-Ping; Xie, Jian-Qun; Wu, Hui; Zhang, Bei-Bei; Wang, Zheng-Tao; Yuan, Jian-Ye; Wu, Xiao-Jun

    2014-12-01

    Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-κB and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin. In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8‑independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-κB. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of Jak2/PI3K/NF-κB/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.

  7. Autocrine stimulation of clear-cell renal carcinoma cell migration in hypoxia via HIF-independent suppression of thrombospondin-1

    Science.gov (United States)

    Bienes-Martínez, Raquel; Ordóñez, Angel; Feijoo-Cuaresma, Mónica; Corral-Escariz, María; Mateo, Gloria; Stenina, Olga; Jiménez, Benilde; Calzada, María J.

    2012-01-01

    Thrombospondin-1 is a matricellular protein with potent antitumour activities, the levels of which determine the fate of many different tumours, including renal carcinomas. However, the factors that regulate this protein remain unclear. In renal carcinomas, hypoxic conditions enhance the expression of angiogenic factors that help adapt tumour cells to their hostile environment. Therefore, we hypothesized that anti-angiogenic factors should correspondingly be dampened. Indeed, we found that hypoxia decreased the thrombospondin-1 protein in several clear cell renal carcinoma cell lines (ccRCC), although no transcriptional regulation was observed. Furthermore, we proved that hypoxia stimulates multiple signals that independently contribute to diminish thrombospondin-1 in ccRCC, which include a decrease in the activity of oxygen-dependent prolylhydroxylases (PHDs) and activation of the PI3K/Akt signalling pathway. In addition, thrombospondin-1 regulation in hypoxia proved to be important for ccRCC cell migration and invasion. PMID:23145312

  8. Geranylated 4-Phenylcoumarins Exhibit Anticancer Effects against Human Prostate Cancer Cells through Caspase-Independent Mechanism.

    Directory of Open Access Journals (Sweden)

    Noor Shahirah Suparji

    Full Text Available Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment. Elucidation on the mode-of-action via protein arrays and western blotting demonstrated death induced without any significant expressions of caspases, Bcl-2 family proteins and cleaved PARP, thus suggesting the involvement of caspase-independent pathways. In identifying autophagy, analysis of GFP-LC3 showed increased punctate in PC-3 cells pre-treated with CQ and treated with DMDP-1. In these cells decreased expression of autophagosome protein, p62 and cathepsin B further confirmed autophagy. In contrary, the DU 145 cells pre-treated with CQ and treated with DMDP-2 has reduced GFP-LC3 punctate although the number of cells with obvious GFP-LC3 puncta was significantly increased in the inhibitor-treated cells. The increase level of p62 suggested leakage of cathepsin B into the cytosol to trigger potential downstream death mediators. This correlated with increased expression of cathepsin B and reduced expression after treatment with its inhibitor, CA074. Also auto-degradation of calpain-2 upon treatment with DMDP-1 &-2 and its inhibitor alone, calpeptin compared with the combination treatment, further confirmed involvement of calpain-2 in PC-3 and DU 145 cells. Treatment with DMDP-1 & -2 also showed up-regulation of total and phosphorylated p53 levels in a time dependent manner. Hence, DMDP-1 & -2 showed ability to activate multiple death pathways involving autophagy, lysosomal and endoplasmic reticulum death

  9. Hepatitis C virus core protein induces apoptosis-like caspase independent cell death

    Directory of Open Access Journals (Sweden)

    Gregor Michael

    2009-12-01

    Full Text Available Abstract Background Hepatitis C virus (HCV associated liver diseases may be related to apoptotic processes. Thus, we investigated the role of different HCV proteins in apoptosis induction as well as their potency to interact with different apoptosis inducing agents. Methods and Results The use of a tightly adjustable tetracycline (Tet-dependent HCV protein expression cell system with the founder osteosarcoma cell line U-2 OS allowed switch-off and on of the endogenous production of HCV proteins. Analyzed were cell lines expressing the HCV polyprotein, the core protein, protein complexes of the core, envelope proteins E1, E2 and p7, and non-structural proteins NS3 and NS4A, NS4B or NS5A and NS5B. Apoptosis was measured mainly by the detection of hypodiploid apoptotic nuclei in the absence or presence of mitomycin C, etoposide, TRAIL and an agonistic anti-CD95 antibody. To further characterize cell death induction, a variety of different methods like fluorescence microscopy, TUNEL (terminal deoxynucleotidyl transferase (TdT-catalyzed deoxyuridinephosphate (dUTP-nick end labeling assay, Annexin V staining, Western blot and caspase activation assays were included into our analysis. Two cell lines expressing the core protein but not the total polyprotein exerted a strong apoptotic effect, while the other cell lines did not induce any or only a slight effect by measuring the hypodiploid nuclei. Cell death induction was caspase-independent since it could not be blocked by zVAD-fmk. Moreover, caspase activity was absent in Western blot analysis and fluorometric assays while typical apoptosis-associated morphological features like the membrane blebbing and nuclei condensation and fragmentation could be clearly observed by microscopy. None of the HCV proteins influenced the apoptotic effect mediated via the mitochondrial apoptosis pathway while only the core protein enhanced death-receptor-mediated apoptosis. Conclusion Our data showed a caspase-independent

  10. Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines

    Science.gov (United States)

    Yu, Vicky; Rahimy, Mehran; Korrapati, Avinaash; Xuan, Yinan; Zou, Angela E.; Krishnan, Aswini R.; Tsui, Tzuhan; Aguilera, Joseph A.; Advani, Sunil; Crotty Alexander, Laura E.; Brumund, Kevin T.; Wang-Rodriguez, Jessica

    2016-01-01

    Objectives Evaluate the cytotoxicity and genotoxicity of short- and long-term e-cigarette vapor exposure on a panel of normal epithelial and head and neck squamous cell carcinoma (HNSCC) cell lines. Materials and Methods HaCaT, UMSCC10B, and HN30 were treated with nicotine-containing and nicotine-free vapor extract from two popular e-cigarette brands for periods ranging from 48 hours to 8 weeks. Cytotoxicity was assessed using Annexin V flow cytometric analysis, trypan blue exclusion, and clonogenic assays. Genotoxicity in the form of DNA strand breaks was quantified using the neutral comet assay and γ-H2AX immunostaining. Results E-cigarette-exposed cells showed significantly reduced cell viability and clonogenic survival, along with increased rates of apoptosis and necrosis, regardless of e-cigarette vapor nicotine content. They also exhibited significantly increased comet tail length and accumulation of γ-H2AX foci, demonstrating increased DNA strand breaks. Conclusion E-cigarette vapor, both with and without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed. PMID:26547127

  11. Radiation could induce p53-independent and cell cycle - unrelated apoptosis in 5-fluorouracil radiosensitized head and neck carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Didelot, C.; Mirjolet, J.F.; Barberi-Heyob, M.; Ramacci, C.; Merlin, J.L. [Centre Alexis Vautrin, Lab. de Recherche en Oncologie, Vandoeuvre-les-Nancy CEDEX (France)

    2002-07-01

    The effect of chemoresistance induction in radio sensitivity and cellular behavior after irradiation remains misunderstood. This study was designed to understand the relationship between radiation-induced cell cycle arrest, apoptosis, and radiosensitivity in KB cell line and KB3 subline selected after 5-fluorouracil (5FU) exposure. Exposure of KB cells to 5FU led to an increase in radiosensitivity. G{sub 2}/M cell cycle arrest was observed in the two cell lines after irradiation. The radioresistant KB cell line reached the maximum arrest two hours before KB3. The cellular exit from this arrest was found to be related to the wild type p53 protein expression induction. After irradiation, only KB3 cell line underwent apoptosis. This apoptosis induction seemed to be independent of G{sub 2}/M arrest exit, which was carried out later. The difference in radiosensitivity between KB and KB3 subline may result therefore from both a difference in apoptosis induction and a difference in G{sub 2}/M arrest maximum duration. Moreover, 5FU exposure has led to an increase in constitutive p53 protein expression, which may be associated with an increase in basal apoptosis cell fraction. Given the existing correlation between radiosensitivity and the percentage of basal apoptosis. the constitutive p53 protein expression may be related to intrinsic radiosensitivity in our cellular model. (author)

  12. Exact, time-independent estimation of clone size distributions in normal and mutated cells.

    Science.gov (United States)

    Roshan, A; Jones, P H; Greenman, C D

    2014-10-06

    Biological tools such as genetic lineage tracing, three-dimensional confocal microscopy and next-generation DNA sequencing are providing new ways to quantify the distribution of clones of normal and mutated cells. Understanding population-wide clone size distributions in vivo is complicated by multiple cell types within observed tissues, and overlapping birth and death processes. This has led to the increased need for mathematically informed models to understand their biological significance. Standard approaches usually require knowledge of clonal age. We show that modelling on clone size independent of time is an alternative method that offers certain analytical advantages; it can help parametrize these models, and obtain distributions for counts of mutated or proliferating cells, for example. When applied to a general birth-death process common in epithelial progenitors, this takes the form of a gambler's ruin problem, the solution of which relates to counting Motzkin lattice paths. Applying this approach to mutational processes, alternative, exact, formulations of classic Luria-Delbrück-type problems emerge. This approach can be extended beyond neutral models of mutant clonal evolution. Applications of these approaches are twofold. First, we resolve the probability of progenitor cells generating proliferating or differentiating progeny in clonal lineage tracing experiments in vivo or cell culture assays where clone age is not known. Second, we model mutation frequency distributions that deep sequencing of subclonal samples produce.

  13. Highly polarized Th17 cells induce EAE via a T-bet independent mechanism.

    Science.gov (United States)

    Grifka-Walk, Heather M; Lalor, Stephen J; Segal, Benjamin M

    2013-11-01

    In the MOG35-55 induced EAE model, autoreactive Th17 cells that accumulate in the central nervous system acquire Th1 characteristics via a T-bet dependent mechanism. It remains to be determined whether Th17 plasticity and encephalitogenicity are causally related to each other. Here, we show that IL-23 polarized T-bet(-/-) Th17 cells are unimpaired in either activation or proliferation, and induce higher quantities of the chemokines RANTES and CXCL2 than WT Th17 cells. Unlike their WT counterparts, T-bet(-/-) Th17 cells retain an IL-17(hi) IFN-γ(neg-lo) cytokine profile following adoptive transfer into syngeneic hosts. This population of highly polarized Th17 effectors is capable of mediating EAE, albeit with a milder clinical course. It has previously been reported that the signature Th1 and Th17 effector cytokines, IFN-γ and IL-17, are dispensable for the development of autoimmune demyelinating disease. The current study demonstrates that the "master regulator" transcription factor, T-bet, is also not universally required for encephalitogenicity. Our results contribute to a growing body of data showing heterogeneity of myelin-reactive T cells and the independent mechanisms they employ to inflict damage to central nervous system tissues, complicating the search for therapeutic targets relevant across the spectrum of individuals with multiple sclerosis.

  14. Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.

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    Alexandre Henriques

    Full Text Available Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS. Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R, survival, disease duration, site of onset and body mass index. Palmitoleate (16:1 and oleate (18:1 levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0 significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05. Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009. In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

  15. DNA double-strand breaks activate ATM independent of mitochondrial dysfunction in A549 cells.

    Science.gov (United States)

    Kalifa, Lidza; Gewandter, Jennifer S; Staversky, Rhonda J; Sia, Elaine A; Brookes, Paul S; O'Reilly, Michael A

    2014-10-01

    Excessive nuclear or mitochondrial DNA damage can lead to mitochondrial dysfunction, decreased energy production, and increased generation of reactive oxygen species (ROS). Although numerous cell signaling pathways are activated when cells are injured, the ataxia telangiectasia mutant (ATM) protein has emerged as a major regulator of the response to both mitochondrial dysfunction and nuclear DNA double-strand breaks (DSBs). Because mitochondrial dysfunction is often a response to excessive DNA damage, it has been difficult to determine whether nuclear and/or mitochondrial DNA DSBs activate ATM independent of mitochondrial dysfunction. In this study, mitochondrial and nuclear DNA DSBs were generated in the A549 human lung adenocarcinoma cell line by infecting with retroviruses expressing the restriction endonuclease PstI fused to a mitochondrial targeting sequence (MTS) or nuclear localization sequence (NLS) and a hemagglutinin antigen epitope tag (HA). Expression of MTS-PstI-HA or NLS-PstI-HA activated the DNA damage response defined by phosphorylation of ATM, the tumor suppressor protein p53 (TP53), KRAB-associated protein (KAP)-1, and structural maintenance of chromosomes (SMC)-1. Phosphorylated ATM and SMC1 were detected in nuclear fractions, whereas phosphorylated TP53 and KAP1 were detected in both mitochondrial and nuclear fractions. PstI also enhanced expression of the cyclin-dependent kinase inhibitor p21 and inhibited cell growth. This response to DNA damage occurred in the absence of detectable mitochondrial dysfunction and excess production of ROS. These findings reveal that DNA DSBs are sufficient to activate ATM independent of mitochondrial dysfunction and suggest that the activated form of ATM and some of its substrates are restricted to the nuclear compartment, regardless of the site of DNA damage.

  16. Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Henriques, Alexandre; Blasco, Hélène; Fleury, Marie-Céline; Corcia, Philippe; Echaniz-Laguna, Andoni; Robelin, Laura; Rudolf, Gabrielle; Lequeu, Thiebault; Bergaentzle, Martine; Gachet, Christian; Pradat, Pierre-François; Marchioni, Eric; Andres, Christian R.; Tranchant, Christine; Gonzalez De Aguilar, Jose-Luis; Loeffler, Jean-Philippe

    2015-01-01

    Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs. PMID:26147510

  17. Independent [Ca2+]i increases and cell proliferation induced by the carcinogen safrole in human oral cancer cells.

    Science.gov (United States)

    Huang, Jong-Khing; Huang, Chun-Jen; Chen, Wei-Chuan; Liu, Shiuh-Inn; Hsu, Shu-Shong; Chang, Hong-Tai; Tseng, Li-Ling; Chou, Chiang-Ting; Chang, Chih-Hung; Jan, Chung-Ren

    2005-07-01

    The effect of the carcinogen safrole on intracellular Ca2+ movement and cell proliferation has not been explored previously. The present study examined whether safrole could alter Ca2+ handling and growth in human oral cancer OC2 cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at a concentration of 325 microM started to increase [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 40% by removing extracellular Ca2+, and was decreased by 39% by nifedipine but not by verapamil or diltiazem. In Ca2+-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) barely induced a [Ca2+]i rise; in contrast, addition of safrole after thapsigargin treatment induced a small [Ca2+]i rise. Neither inhibition of phospholipase C with 2 microM U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 1 microM safrole did not alter cell proliferation, but incubation with 10-1000 microM safrole increased cell proliferation by 60+/-10%. This increase was not reversed by pre-chelating Ca2+ with 10 microM of the Ca2+ chelator BAPTA. Collectively, the data suggest that in human oral cancer cells, safrole induced a [Ca2+]i rise by causing release of stored Ca2+ from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion and by inducing Ca2+ influx via nifedipine-sensitive Ca2+ entry. Furthermore, safrole can enhance cell growth in a Ca2+-independent manner.

  18. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells

    Science.gov (United States)

    Peter, Yakov; Sen, Namita; Levantini, Elena; Keller, Steven; Ingenito, Edward P; Ciner, Aaron; Sackstein, Robert; Shapiro, Steven D

    2015-01-01

    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted 37% of the total culture at day 14, yielding a mixed yet conserved population that recapitulated RNA expression patterns of the healthy lung. AICs exhibited rapid proliferation manifested by a marked 60-fold increase in cell numbers by day 21. Over 50% of the AIC population was cKit+ or double-positive for CD45+ and CD11b+ antigenic determinants, consistent with cells of hematopoietic origin. The latter subset was found to be enriched with prosurfactant protein-C and SCGB1A1 expressing putative stem cells and with aquaporin-5 producing cells, characteristic of terminally differentiated alveolar epithelial type-1 pneumocytes. AICs undergo remodeling to form a cellular lining at the air/gel interface, and TGFβ1 treatment modifies protein expression, implying direct-differentiation of this population. These data confirm the active participation of clonogenic hematopietic stem cells in a mammalian model of lung repair and validate mixed stem/somatic cell cultures, which embrace sustained cell viability, proliferation, and differentiation, for use in studies of compensatory pulmonary growth. PMID:22585451

  19. Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Woollard, Wesley J; Kalaivani, Nithyha P; Jones, Christine L; Roper, Catherine; Tung, Lam; Lee, Jae Jin; Thomas, Bjorn R; Tosi, Isabella; Ferreira, Silvia; Beyers, Carl Z; McKenzie, Robert C T; Butler, Rosie M; Lorenc, Anna; Whittaker, Sean J; Mitchell, Tracey J

    2016-06-01

    Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment.

  20. The transfusion medicine we want.

    Science.gov (United States)

    2011-01-01

    The Associação Brasileira de Hematologia e Hemoterapia (ABHH), through its Board of Directors, hosted a national symposium called "Forum: The Transfusion Medicine we want", to discuss proposed policies and techniques related to the area. This meeting was held in São Paulo on August 19 and 20, 2010, with the participation of experts, authorities and representatives of organized groups of patients and users. The discussions were organized around three specific issues selected from over 100 suggestions sent to the ABHH through public consultation on the web: 1. Strategies; 2. Financing; 3. Blood products. A plenary session, held at the end of the meeting, adopted recommendations that are relevant to the different discussion topics.This document contains actions proposed by the ABHH to meet the demands discussed.

  1. Notification of transfusion transmitted infection.

    Science.gov (United States)

    Choudhury, Lincoln P; Tetali, Shailaja

    2008-01-01

    The National Blood Policy of India, 2002, advocates the disclosure of results of transfusion transmitted infections (TTI) to blood donors. However, in the absence of well-defined notification processes, and in order to avoid serious consequences resulting from unguided disclosure, blood bank personnel discard blood that is TTI-positive. We report on a survey of 105 voluntary blood donors in Kerala. Only two out of three participants had filled the donor form in the last year. Only half were aware that the blood bank was supposed to inform them if they tested positive for TTI. Fifty-seven per cent of donors wanted to be informed every time they donated blood, irrespective of a positive or negative result.

  2. Decreasing the critical value of hemoglobin required for physician notification reduces the rate of blood transfusions

    Directory of Open Access Journals (Sweden)

    Larson EA

    2016-06-01

    Full Text Available Eric A Larson,1 Paul A Thompson,1,2 Zachary K Anderson,3 Keith A Anderson,4 Roxana A Lupu,1 Vicki Tigner,5 Wendell W Hoffman6,7 1Department of Internal Medicine, 2Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, 3Department of Internal Medicine, Fairview Health Services, Edina, MN, 4Department of Laboratory Medicine, Sanford School of Medicine, University of South Dakota, 5Medical Staff Services, 6Department of Infectious Disease, Sanford Health, Sanford USD Medical Center, 7Department of Infectious Disease, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USAAbstract: Red blood cell transfusions have been cited as one of the most overused therapeutic interventions in the USA. Excessively aggressive transfusion practices may be driven by mandatory physician notification of critical hemoglobin values that do not generally require transfusion. We examined the effect of decreasing the critical value of hemoglobin from 8 to 7 g/dL at our institution. Along with this change, mandatory provider notification for readings between 7 and 8 g/dL was rescinded. Transfusion rates were compared retrospectively during paired 5-month periods for patients presenting in three key hemoglobin ranges (6.00–6.99, 7.00–7.99, and 8.00–8.99 g/dL. A change in transfusion practices was hypothesized in the 7–8 g/dL range, which was no longer labeled critical and for which mandated physician calls were rescinded. Transfusion rates showed a statistically significant 8% decrease (P≤0.0001 during the 5-month period post change in our transfusion practices. This decrease in the 7.00–7.99 g/dL range was significantly greater than the 2% decrease observed in either the 6–6.99 g/dL (P=0.0017 or 8–8.99 g/dL (P≤0.0001 range. Cost savings of up to $700,000/year were extrapolated from our results showing 491 fewer units of red blood cells transfused during the 5-month post change. These cost

  3. Alcohol-positive multiple trauma patients with and without blood transfusion: an outcome analysis

    Directory of Open Access Journals (Sweden)

    Stuttmann Ralph

    2009-03-01

    Full Text Available Abstract Background Blood transfusion is a common therapy for multiple trauma patients, and is often performed soon after hospital admission. It is unclear whether the need for a blood transfusion in multiply injured patients presenting with a positive blood alcohol concentration (BAC is associated with increased morbidity/mortality, since their risk behavior differs significantly from patients with a negative BAC. In this study, we evaluated the role of blood transfusion in the treatment of BAC-positive multiple trauma patients. Patients In a three-year period, 164 patients at a single trauma center presented with a positive BAC, and 145 met the inclusion criteria for further evaluation and regression analysis. We compared patients who were transfused (n = 76 with those who were not transfused (n = 69. Results In both groups, the most common causes of trauma were traffic accidents and falls. Most patients were admitted to the hospital from the scene of the accident (77.2% and were male (89.0%. Transfused patients had a lower GCS (p ≤ .001 and her ISS (p ≤ .001, were more likely to have severe head injuries (p ≤ .001, tended to have higher BACs (p = .053, had lower hemoglobin levels and prothrombin times in the first 24 hours (p ≤ .001, had lower lactate levels, had higher rates of intubation (p ≤ .001 and ICU admission, and had longer ICU stays and artificial ventilation times (p ≤ .001. Mortality was significantly higher in transfused patients (n = 15 vs. n = 3, p ≤ .001. Non-survivors were more likely to have severe head injuries; be intubated and ventilated; be older; have higher ISS scores, lactate levels, and numbers of transfusions in the first 24 hours; and have lower GCS scores, hemoglobin measurements, and prothrombin levels. In a binary logistic regression model, only age (p = .009 and ISS (p = .004 independently predicted mortality. Conclusion In our single-center study, the BAC of multiple trauma patients and the

  4. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway

    Institute of Scientific and Technical Information of China (English)

    Hongliang Wang; Peng Yang; Kangtai Liu; Feng Guo; Yanli Zhang; Gongyi Zhang; Chengyu Jiang

    2008-01-01

    While severe acute respiratory syndrome coronavirus (SARS-CoV)fwas initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that virus entry may also involve endocytosis. We have found that SARS-CoV enters cells via pH- and receptor-dependent endocytosis. Treatment of cells with either SARS-CoV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic pathway inhibitors and dominant-negative Eps15 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.

  5. Inflammasome-independent modulation of cytokine response by autophagy in human cells.

    Directory of Open Access Journals (Sweden)

    Tania O Crişan

    Full Text Available Autophagy is a cell housekeeping mechanism that has recently received attention in relation to its effects on the immune response. Genetic studies have identified candidate loci for Crohn's disease susceptibility among autophagy genes, while experiments in murine macrophages from ATG16L1 deficient mice have shown that disruption of autophagy increases processing of IL-1β and IL-18 through an inflammasome-dependent manner. Using complementary approaches either inducing or inhibiting autophagy, we describe modulatory effects of autophagy on proinflammatory cytokine production in human cells. Inhibition of basal autophagy in human peripheral blood mononuclear cells (PBMCs significantly enhances IL-1β after stimulation with TLR2 or TLR4 ligands, while at the same time reducing the production of TNFα. In line with this, induction of autophagy by starvation inhibited IL-1β production. These effects of autophagy were not exerted at the processing step, as inflammasome activation was not influenced. In contrast, the effect of autophagy on cytokine production was on transcription level, and possibly involving the inhibition of p38 mitogen activated protein kinase (MAPK phosphorylation. In conclusion, autophagy modulates the secretion of proinflammatory cytokines in human cells through an inflammasome-independent pathway, and this is a novel mechanism that may be targeted in inflammatory diseases.

  6. The impact of blood transfusion on perioperative outcomes following gastric cancer resection: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database

    Science.gov (United States)

    Elmi, Maryam; Mahar, Alyson; Kagedan, Daniel; Law, Calvin H.L.; Karanicolas, Paul J.; Lin, Yulia; Callum, Jeannie; Coburn, Natalie G.; Hallet, Julie

    2016-01-01

    Background Red blood cell transfusions (RBCT) carry risk of transfusion-related immunodulation that may impact postoperative recovery. This study examined the association between perioperative RBCT and short-term postoperative outcomes following gastrectomy for gastric cancer. Methods Using the American College of Surgeons National Surgical Quality Improvement Program database, we compared outcomes of patients (transfused v. nontransfused) undergoing elective gastrectomy for gastric cancer (2007–2012). Outcomes were 30-day major morbidity, mortality and length of stay. The association between perioperative RBCT and outcomes was estimated using modified Poisson, logistic, or negative binomial regression. Results Of the 3243 patients in the entire cohort, we included 2884 patients with nonmissing data, of whom 535 (18.6%) received RBCT. Overall 30-day major morbidity and mortality were 20% and 3.5%, respectively. After adjustment for baseline and clinical characteristics, RBCT was independently associated with increased 30-day mortality (relative risk [RR] 3.1, 95% confidence interval [CI] 1.9–5.0), major morbidity (RR 1.4, 95% CI 1.2–1.8), length of stay (RR 1.2, 95% CI 1.1–1.2), infections (RR 1.4, 95% CI 1.1–1.6), cardiac complications (RR 1.8, 95% CI 1.0–3.2) and respiratory failure (RR 2.3, 95% CI 1.6–3.3). Conclusion Red blood cell transfusions are associated with worse postoperative short-term outcomes in patients with gastric cancer. Blood management strategies are needed to reduce the use of RBCT after gastrectomy for gastric cancer. PMID:27668330

  7. Biomechanics of P-selectin PSGL-1 bonds: Shear threshold and integrin-independent cell adhesion

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    Xiao, Zhihua; Goldsmith, Harry L.; MacIntosh, Fiona A.; Shankaran, Harish; Neelamegham, Sriram

    2006-03-01

    Platelet-leukocyte adhesion may contribute to thrombosis and inflammation. We examined the heterotypic interaction between unactivated neutrophils and either thrombin receptor activating peptide (TRAP) stimulated platelets or P-selectin bearing beads (Ps-beads) in suspension. Cone-plate viscometers were used to apply controlled shear rates from 14-3000/s. Platelet-neutrophil and bead-neutrophil adhesion analysis was performed using both flow cytometry and high-speed videomicroscopy. We observed that while blocking antibodies against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1) alone inhibited platelet-neutrophil adhesion by ~60% at 140/s, these reagents completely blocked adhesion at 3000/s. Anti-Mac-1 alone did not alter platelet-neutrophil adhesion rates at any shear rate, though in synergy with selectin antagonists it abrogated cell binding. Unstimulated neutrophils avidly bound Ps-beads and activated platelets in an integrin-independent manner, suggesting that purely selectin-dependent cell adhesion is possible. In support of this, antagonists against P-selectin or PSGL-1 dissociated previously formed platelet-neutrophil and Ps-bead neutrophil aggregates under shear in a variety of experimental systems, including in assays performed with whole blood. In studies where medium viscosity and shear rate were varied, a subtle shear threshold for P-selectin PSGL-1 binding was also noted at shear rates<100/s and at force loading rates of ~300pN/sec. Results are discussed in light of biophysical computations that characterize the collision between unequal size particles in linear shear flow. Overall, our studies reveal an integrin-independent regime for cell adhesion that may be physiologically relevant.

  8. Air bubble contact with endothelial cells causes a calcium-independent loss in mitochondrial membrane potential.

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    Peter Sobolewski

    Full Text Available OBJECTIVE: Gas microembolism remains a serious risk associated with surgical procedures and decompression. Despite this, the signaling consequences of air bubbles in the vasculature are poorly understood and there is a lack of pharmacological therapies available. Here, we investigate the mitochondrial consequences of air bubble contact with endothelial cells. METHODS AND RESULTS: Human umbilical vein endothelial cells were loaded with an intracellular calcium indicator (Fluo-4 and either a mitochondrial calcium indicator (X-Rhod-1 or mitochondrial membrane potential indicator (TMRM. Contact with 50-150 µm air bubbles induced concurrent rises in intracellular and mitochondrial calcium, followed by a loss of mitochondrial membrane potential. Pre-treating cells with 1 µmol/L ruthenium red, a TRPV family calcium channel blocker, did not protect cells from the mitochondrial depolarization, despite blocking the intracellular calcium response. Mitigating the interactions between the air-liquid interface and the endothelial surface layer with 5% BSA or 0.1% Pluronic F-127 prevented the loss of mitochondrial membrane potential. Finally, inhibiting protein kinase C-α (PKCα, with 5 µmol/L Gö6976, protected cells from mitochondrial depolarization, but did not affect the intracellular calcium response. CONCLUSIONS: Our results indicate that air bubble contact with endothelial cells activates a novel, calcium-independent, PKCα-dependent signaling pathway, which results in mitochondrial depolarization. As a result, mitochondrial dysfunction is likely to be a key contributor to the pathophysiology of gas embolism injury. Further, this connection between the endothelial surface layer and endothelial mitochondria may also play an important role in vascular homeostasis and disease.

  9. HDAC1 inactivation induces mitotic defect and caspase-independent autophagic cell death in liver cancer.

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    Hong Jian Xie

    Full Text Available Histone deacetylases (HDACs are known to play a central role in the regulation of several cellular properties interlinked with the development and progression of cancer. Recently, HDAC1 has been reported to be overexpressed in hepatocellular carcinoma (HCC, but its biological roles in hepatocarcinogenesis remain to be elucidated. In this study, we demonstrated overexpression of HDAC1 in a subset of human HCCs and liver cancer cell lines. HDAC1 inactivation resulted in regression of tumor cell growth and activation of caspase-independent autophagic cell death, via LC3B-II activation pathway in Hep3B cells. In cell cycle regulation, HDAC1 inactivation selectively induced both p21(WAF1/Cip1 and p27(Kip1 expressions, and simultaneously suppressed the expression of cyclin D1 and CDK2. Consequently, HDAC1 inactivation led to the hypophosphorylation of pRb in G1/S transition, and thereby inactivated E2F/DP1 transcription activity. In addition, we demonstrated that HDAC1 suppresses p21(WAF1/Cip1 transcriptional activity through Sp1-binding sites in the p21(WAF1/Cip1 promoter. Furthermore, sustained suppression of HDAC1 attenuated in vitro colony formation and in vivo tumor growth in a mouse xenograft model. Taken together, we suggest the aberrant regulation of HDAC1 in HCC and its epigenetic regulation of gene transcription of autophagy and cell cycle components. Overexpression of HDAC1 may play a pivotal role through the systemic regulation of mitotic effectors in the development of HCC, providing a particularly relevant potential target in cancer therapy.

  10. [Blood transfusion and supply chain management safety].

    Science.gov (United States)

    Quaranta, Jean-François; Caldani, Cyril; Cabaud, Jean-Jacques; Chavarin, Patricia; Rochette-Eribon, Sandrine

    2015-02-01

    The level of safety attained in blood transfusion now makes this a discipline better managed care activities. This was achieved both by scientific advances and policy decisions regulating and supervising the activity, as well as by the quality system, which we recall that affects the entire organizational structure, responsibilities, procedures, processes and resources in place to achieve quality management. So, an effective quality system provides a framework within which activities are established, performed in a quality-focused way and continuously monitored to improve outcomes. This system quality has to irrigate all the actors of the transfusion, just as much the establishments of blood transfusion than the health establishments.

  11. Quality Assessment of Established and Emerging Blood Components for Transfusion

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    Jason P. Acker

    2016-01-01

    Full Text Available Blood is donated either as whole blood, with subsequent component processing, or through the use of apheresis devices that extract one or more components and return the rest of the donation to the donor. Blood component therapy supplanted whole blood transfusion in industrialized countries in the middle of the twentieth century and remains the standard of care for the majority of patients receiving a transfusion. Traditionally, blood has been processed into three main blood products: red blood cell concentrates; platelet concentrates; and transfusable plasma. Ensuring that these products are of high quality and that they deliver their intended benefits to patients throughout their shelf-life is a complex task. Further complexity has been added with the development of products stored under nonstandard conditions or subjected to additional manufacturing steps (e.g., cryopreserved platelets, irradiated red cells, and lyophilized plasma. Here we review established and emerging methodologies for assessing blood product quality and address controversies and uncertainties in this thriving and active field of investigation.

  12. Quality Assessment of Established and Emerging Blood Components for Transfusion

    Science.gov (United States)

    Marks, Denese C.

    2016-01-01

    Blood is donated either as whole blood, with subsequent component processing, or through the use of apheresis devices that extract one or more components and return the rest of the donation to the donor. Blood component therapy supplanted whole blood transfusion in industrialized countries in the middle of the twentieth century and remains the standard of care for the majority of patients receiving a transfusion. Traditionally, blood has been processed into three main blood products: red blood cell concentrates; platelet concentrates; and transfusable plasma. Ensuring that these products are of high quality and that they deliver their intended benefits to patients throughout their shelf-life is a complex task. Further complexity has been added with the development of products stored under nonstandard conditions or subjected to additional manufacturing steps (e.g., cryopreserved platelets, irradiated red cells, and lyophilized plasma). Here we review established and emerging methodologies for assessing blood product quality and address controversies and uncertainties in this thriving and active field of investigation. PMID:28070448

  13. Quality Assessment of Established and Emerging Blood Components for Transfusion.

    Science.gov (United States)

    Acker, Jason P; Marks, Denese C; Sheffield, William P

    2016-01-01

    Blood is donated either as whole blood, with subsequent component processing, or through the use of apheresis devices that extract one or more components and return the rest of the donation to the donor. Blood component therapy supplanted whole blood transfusion in industrialized countries in the middle of the twentieth century and remains the standard of care for the majority of patients receiving a transfusion. Traditionally, blood has been processed into three main blood products: red blood cell concentrates; platelet concentrates; and transfusable plasma. Ensuring that these products are of high quality and that they deliver their intended benefits to patients throughout their shelf-life is a complex task. Further complexity has been added with the development of products stored under nonstandard conditions or subjected to additional manufacturing steps (e.g., cryopreserved platelets, irradiated red cells, and lyophilized plasma). Here we review established and emerging methodologies for assessing blood product quality and address controversies and uncertainties in this thriving and active field of investigation.

  14. Human regulatory T cell suppressive function is independent of apoptosis induction in activated effector T cells.

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    Yvonne Vercoulen

    Full Text Available BACKGROUND: CD4(+CD25(+FOXP3(+ Regulatory T cells (Treg play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector immune responses in human. Experiments in mice demonstrated that Treg restrict effector T cell (Teff responses by deprivation of the growth factor IL-2 through Treg consumption, resulting in apoptosis of Teff. PRINCIPAL FINDINGS: In this study we investigated the relevance of Teff apoptosis induction to human Treg function. To this end, we studied naturally occurring Treg (nTreg from peripheral blood of healthy donors, and, to investigate Treg function in inflammation in vivo, Treg from synovial fluid of Juvenile Idiopathic Arthritis (JIA patients (SF-Treg. Both nTreg and SF-Treg suppress Teff proliferation and cytokine production efficiently as predicted. However, in contrast with murine Treg, neither nTreg nor SF-Treg induce apoptosis in Teff. Furthermore, exogenously supplied IL-2 and IL-7 reverse suppression, but do not influence apoptosis of Teff. SIGNIFICANCE: Our functional data here support that Treg are excellent clinical targets to counteract autoimmune diseases. For optimal functional outcome in human clinical trials, future work should focus on the ability of Treg to suppress proliferation and cytokine production of Teff, rather than induction of Teff apoptosis.

  15. Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells.

    Science.gov (United States)

    Franquesa, M; Mensah, F K; Huizinga, R; Strini, T; Boon, L; Lombardo, E; DelaRosa, O; Laman, J D; Grinyó, J M; Weimar, W; Betjes, M G H; Baan, C C; Hoogduijn, M J

    2015-03-01

    Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system in multiple ways. Modulation of the immune system by MSC is believed to be a therapeutic option for autoimmune disease and transplant rejection. In recent years, B cells have moved into the focus of the attention as targets for the treatment of immune disorders. Current B-cell targeting treatment is based on the indiscriminate depletion of B cells. The aim of this study was to examine whether human adipose tissue-derived MSC (ASC) interact with B cells to affect their proliferation, differentiation, and immune function. ASC supported the survival of quiescent B cells predominantly via contact-dependent mechanisms. Coculture of B cells with activated T helper cells led to proliferation and differentiation of B cells into CD19(+) CD27(high) CD38(high) antibody-producing plasmablasts. ASC inhibited the proliferation of B cells and this effect was dependent on the presence of T cells. In contrast, ASC directly targeted B-cell differentiation, independently of T cells. In the presence of ASC, plasmablast formation was reduced and IL-10-producing CD19(+) CD24(high) CD38(high) B cells, known as regulatory B cells, were induced. These results demonstrate that ASC affect B cell biology in vitro, suggesting that they can be a tool for the modulation of the B-cell response in immune disease.

  16. Influence of antiplatelet-anticoagulant drugs on the need of blood components transfusion after vesical transurethral resection

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    Alvaro Julio Virseda-Rodríguez

    2015-07-01

    Full Text Available Aims: The effect of the antithrombotic preventive therapy on haemorrhage keeps uncertain. We investigate the influence of the antiplatelet and anticoagulant drugs (AP/AC drugs on the transfusion requirement after vesical transurethral resection (VTUR. We also describe the epidemiology of the blood components transfusion in our department. Materials and Methods: Retrospective observational study of a series of patients needing blood transfusion at the Urology Department between June 2010 and June 2013. Selection of 100 consecutive patients who were transfused after VTUR due to bladder transitional cell carcinoma (BTCC (group A = GA. Control group: 100 consecutive patients who underwent VTUR due to BTCC and were not transfused (group B = GB. Transfusion criteria: Haemoglobin < 8 g/dl + anaemia symptoms. Age, gender, associated AP/AC treatment, secondary diagnoses, toxics, tumour stage and grade were analysed. Results: 212 patients required transfusion of a blood component. 169 were men (79% and 43 women (21%. Median age 77.59 years (SD 9.42, range 50-92. Secondary diagnoses: Diabetes Mellitus 64%, high blood pressure 77%, dyslipidemia 52%. 60% of patients were previously treated with AP/AC drugs. Average Haemoglobin pre-transfusion values: 7.4 g/dl (DE ± 0.7. Average Haemoglobin post-transfusion values: 8.9 g/Dl (DE ± 0.72. Most frequent transfusion indications were bladder cancer (37%, kidney cancer (11%, prostate cancer (8%, benign prostatic hyperplasia (BHP (8%, other urological diagnoses (36%. Intraoperative transfusions indicated by the anaesthesiologist: kidney cancer (33%, BPH (28%. Patients who underwent VTUR due to BTCC were older in GA (77.59 years SD 9.42 than in GB (68.98 years SD 11.78 (p = 0.0001. Similar gender distribution (15 women in GA and 24 in GB. Less patients were asked to keep their treatment with ASA 100mg (AcetylSalicylicAcid in GA (25.64% than in GB (50% (p = 0.0330. More aggressive tumour grade in GA (p = 0.0003 and

  17. Blood transfusion in the para-Bombay phenotype.

    Science.gov (United States)

    Lin-Chu, M; Broadberry, R E

    1990-08-01

    The H-deficient phenotypes found in Chinese so far, have all been secretors of soluble blood group substances in saliva. The corresponding isoagglutinin activity (e.g. anti-B in OB(Hm) persons) has been found to be weak in all cases. To determine the clinical significance of these weak isoagglutinins 51Cr red cell survival tests were performed on three OB(Hm) individuals transfused with small volumes (4 ml) of groups B and O RBC. Rapid destruction of most of the RBC occurred whether or not the isoagglutinins of the OB(Hm) individuals were indirect antiglobulin test (IAGT) reactive. When a larger volume (54 ml packed RBC) of group B cells (weakly incompatible by IAGT) was transfused to another OB(Hm) individual with IAGT active anti-HI, the survival of the transfused RBC was 93% at 24 h, with 30% of the RBC remaining in the circulation at 28 d in contrast to 76% as would be expected if the survival was normal. Therefore when whole units of blood of normal ABO blood groups, compatible by IAGT, are transfused, the survival is expected to be almost normal. These weak isoagglutinins may not be very clinically significant and we suggest that when para-Bombay blood is not available, the compatibility testing for OA(Hm) persons should be performed with group A and group O packed RBC; OB(Hm) with group B and group O packed RBC: OAB(Hm) with groups A, B, AB and O packed RBC. For cross matching, the indirect antiglobulin test by a prewarmed technique should be used.

  18. Early, Prehospital Activation of the Walking Blood Bank Based on Mechanism of Injury Improves Time to Fresh Whole Blood Transfusion.

    Science.gov (United States)

    Bassett, Aaron K; Auten, Jonathan D; Zieber, Tara J; Lunceford, Nicole L

    2016-01-01

    Balanced component therapy (BCT) remains the mainstay in trauma resuscitation of the critically battle injured. In austere medical environments, access to packed red blood cells, apheresis platelets, and fresh frozen plasma is often limited. Transfusion of warm, fresh whole blood (FWB) has been used to augment limited access to full BCT in these settings. The main limitation of FWB is that it is not readily available for transfusion on casualty arrival. This small case series evaluates the impact early, mechanism-of-injury (MOI)-based, preactivation of the walking blood bank has on time to transfusion. We report an average time of 18 minutes to FWB transfusion from patient arrival. Early activation of the walking blood bank based on prehospital MOI may further reduce the time to FWB transfusion.

  19. SHOT conference report 2016: serious hazards of transfusion - human factors continue to cause most transfusion-related incidents.

    Science.gov (United States)

    Bolton-Maggs, P H B

    2016-12-01

    The Annual SHOT Report for incidents reported in 2015 was published on 7 July at the SHOT symposium. Once again, the majority of reports (77·7%) were associated with mistakes ('human factors'). Pressures and stress in the hospital environment contributed to several error reports. There were 26 deaths where transfusion played a part, one due to haemolysis from anti-Wr(a) (units issued electronically). The incidence of haemolysis due to this antibody has increased in recent years. Transfusion-associated circulatory overload is the most common contributor to death and major morbidity. Reports of delays to transfusion have increased, some caused by the failure of correct patient identification. There were seven ABO-incompatible red cell transfusions (one death) with an additional six to allogeneic stem cell transplant recipients. Near-miss reporting and analysis is useful and demonstrated nearly 300 instances of wrong blood in tube, which could have resulted in ABO-incompatible transfusion had the error not been detected. Errors with anti-D immunoglobulin continue, and preliminary data from the new survey of new anti-D found in pregnancy has shown that sensitisation occurs in some women even with apparently 'ideal' care. For the first time, the SHOT report now incorporates a chapter on donor events.

  20. Fenugreek induced apoptosis in breast cancer MCF-7 cells mediated independently by fas receptor change.

    Science.gov (United States)

    Alshatwi, Ali Abdullah; Shafi, Gowhar; Hasan, Tarique Noorul; Syed, Naveed Ahmed; Khoja, Kholoud Khalid

    2013-01-01

    Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes, high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties, although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extract from Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF- 7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in the presence of FME at 65 μg/mL for 24 and 48 hours. FME induced apoptosis was mediated by the death receptor pathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FME induced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, as well as p53 interdependently.

  1. Circulation-Independent Differentiation Pathway from Extraembryonic Mesoderm toward Hematopoietic Stem Cells via Hemogenic Angioblasts

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    Yosuke Tanaka

    2014-07-01

    Full Text Available A large gap exists in our understanding of the course of differentiation from mesoderm to definitive hematopoietic stem cells (HSCs. Previously, we reported that Runx1+ cells in embryonic day 7.5 (E7.5 embryos contribute to the hemogenic endothelium in the E10.5 aorta-gonad-mesonephros (AGM region and HSCs in the adult bone marrow. Here, we show that two Runx1+ populations subdivided by Gata1 expression exist in E7.5 embryos. The hemogenic endothelium and the HSCs are derived only from the Runx1+Gata1− population. A subset of this population moves from the extra- to intraembryonic region during E7.5–E8.0, where it contributes to the hemogenic endothelium of the dorsal aorta (DA. Migration occurs before the heartbeat is initiated, and it is independent of circulation. This suggests a developmental trajectory from Runx1+ cells in the E7.5 extraembryonic region to definitive HSCs via the hemogenic endothelium.

  2. Neisseria cinerea isolates can adhere to human epithelial cells by type IV pilus-independent mechanisms.

    Science.gov (United States)

    Wörmann, Mirka E; Horien, Corey L; Johnson, Errin; Liu, Guangyu; Aho, Ellen; Tang, Christoph M; Exley, Rachel M

    2016-03-01

    In pathogenic Neisseria species the type IV pili (Tfp) are of primary importance in host-pathogen interactions. Tfp mediate initial bacterial attachment to cell surfaces and formation of microcolonies via pilus-pilus interactions. Based on genome analysis, many non-pathogenic Neisseria species are predicted to express Tfp, but aside from studies on Neisseria elongata, relatively little is known about the formation and function of pili in these organisms. Here, we have analysed pilin expression and the role of Tfp in Neisseria cinerea. This non-pathogenic species shares a close taxonomic relationship to the pathogen Neisseria meningitidis and also colonizes the human oropharyngeal cavity. Through analysis of non-pathogenic Neisseria genomes we identified two genes with homology to pilE, which encodes the major pilin of N. meningitidis. We show which of the two genes is required for Tfp expression in N. cinerea and that Tfp in this species are required for DNA competence, similar to other Neisseria. However, in contrast to the meningococcus, deletion of the pilin gene did not impact the association of N. cinerea to human epithelial cells, demonstrating that N. cinerea isolates can adhere to human epithelial cells by Tfp-independent mechanisms.

  3. Tuning 3D Collagen Matrix Stiffness Independently of Collagen Concentration Modulates Endothelial Cell Behavior

    Science.gov (United States)

    Mason, Brooke N.; Starchenko, Alina; Williams, Rebecca M.; Bonassar, Lawrence J.; Reinhart-King, Cynthia A.

    2012-01-01

    Numerous studies have described the effects of matrix stiffening on cell behavior using two dimensional (2D) synthetic surfaces; however less is known about the effects of matrix stiffening on cells embedded in three dimensional (3D) in vivo-like matrices. A primary limitation in investigating the effects of matrix stiffness in 3D is the lack of materials that can be tuned to control stiffness independently of matrix density. Here, we use collagen-based scaffolds where the mechanical properties are tuned using non-enzymatic glycation of the collagen in solution, prior to polymerization. Collagen solutions glycated prior to polymerization result in collagen gels with a 3-fold increase in compressive modulus without significant changes to the collagen architecture. Using these scaffolds, we show that endothelial cell spreading increases with matrix stiffness, as does the number and length of angiogenic sprouts and the overall spheroid outgrowth. Differences in sprout length are maintained even when the receptor for advanced glycation endproducts is inhibited. Our results demonstrate the ability to de-couple matrix stiffness from matrix density and structure in collagen gels, and that increased matrix stiffness results in increased sprouting and outgrowth. PMID:22902816

  4. ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1.

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    Eyal Kalie

    Full Text Available Melanosomes are lysosome-related organelles that serve as specialized sites of melanin synthesis and storage in melanocytes. The progression of melanosomes through the different stages of their formation requires trafficking of specific proteins and membrane constituents in a sequential manner, which is likely to deploy ubiquitous cellular machinery along with melanocyte-specific proteins. Recent evidence revealed a connection between melanogenesis and the autophagy machinery, suggesting a novel role for members of the latter in melanocytes. Here we focused on ULK1, a key autophagy protein which is negatively regulated by mTORC1, to assess its potential role in melanogenesis in MNT-1 cells. We found that ULK1 depletion causes an increase in melanin levels, suggesting an inhibitory function for this protein in melanogenesis. Furthermore, this increase was accompanied by increased transcription of MITF (microphthalmia-associated transcription factor and tyrosinase and by elevated protein levels of tyrosinase, the rate-limiting factor in melanin biogenesis. We also provide evidence to show that ULK1 function in this context is independent of the canonical ULK1 autophagy partners, ATG13 and FIP200. Furthermore we show that regulation of melanogenesis by ULK1 is independent of mTORC1 inhibition. Our data thus provide intriguing insights regarding the involvement of the key regulatory autophagy machinery in melanogenesis.

  5. Blood doping: the flip side of transfusion and transfusion alternatives.

    Science.gov (United States)

    Cacic, Daniel Limi; Hervig, Tor; Seghatchian, Jerard

    2013-08-01

    Blood doping in sports has been a hot topic of present. Longitudinal follow up of hematological parameters in different endurance sports, during the 1990s and early 2000s, has provided considerable suspicions about extensive blood manipulation, with performance enhancing effects. Recent doping revelations in the media also prove that blood doping is not an anticipated myth but it is, in fact, real. Erythropoiesis stimulating agents and autologous blood transfusions are used in synergy with substantial effect on the maximum oxygen uptake and delivery to muscles. Whilst both methods of blood manipulation represent a potential health hazard, in the context of an elevated hematocrit, nevertheless despite a number of suspicious deaths amongst athletes, this has not yet been fully documented. A reliable test for detection of recombinant human erythropoietin was implemented in 2000, but this is probably circumvented by microdose regimens. The Athlete's Biological Passport represents the progeny of the idea of an indirect approach based on long term monitoring of hematological parameters, thus making it possible to detect autologous blood doping and erythropoietin use after the substance is excreted. Nevertheless with advances in anti-doping measures it is possible that the levels of excretion of substances used can be masked. Clearly more sensitive and specific diagnostic tools and research/development in these areas of major concern are warranted, which, combined with changes in the athlete's attitude, will help in reaching the vision of fair play.

  6. Prolonged induction activates Cebpα independent adipogenesis in NIH/3T3 cells.

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    Hsiao-Yun Shao

    Full Text Available BACKGROUND: 3T3-L1 cells are widely used to study adipogenesis and insulin response. Their adipogenic potential decreases with time in the culture. Expressing exogenous genes in 3T3-L1 cells can be challenging. This work tries to establish and characterize an alternative model of cultured adipocytes that is easier to work with than the 3T3-L1 cells. METHODOLOGY/PRINCIPAL FINDINGS: INDUCED CELLS WERE IDENTIFIED AS ADIPOCYTES BASED ON THE FOLLOWING THREE CHARACTERISTICS: (1 Accumulation of triglyceride droplets as demonstrated by oil red O stain. (2 Transport rate of 2-deoxyglucose increased after insulin stimulation. (3 Expression of fat specific genes such as Fabp4 (aP2, Slc2a4 (Glut4 and Pparg (PPARγ. Among the cell lines induced under different conditions in this study, only NIH/3T3 cells differentiated into adipocytes after prolonged incubation in 3T3-L1 induction medium containing 20% instead of 10% fetal bovine serum. Rosiglitazone added to the induction medium shortened the incubation period from 14 to 7 days. The PI3K/AKT pathway showed similar changes upon insulin stimulation in these two adipocytes. C/EBPα mRNA was barely detectable in NIH/3T3 adipocytes. NIH/3T3 adipocytes induced in the presence of rosiglitazone showed higher 2-deoxyglucose transport rate after insulin stimulation, expressed less Agt (angiotensinogen and more PPARγ. Knockdown of C/EBPα using shRNA blocked 3T3-L1 but not NIH/3T3 cell differentiation. Mouse adipose tissues from various anatomical locations showed comparable levels of C/EBPα mRNA. CONCLUSIONS/SIGNIFICANCE: NIH/3T3 cells were capable of differentiating into adipocytes without genetic engineering. They were an adipocyte model that did not require the reciprocal activation between C/EBPα and PPARγ to differentiate. Future studies in the C/EBPα independent pathways leading to insulin responsiveness may reveal new targets to diabetes treatment.

  7. Cancer incidence in blood transfusion recipients

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Edgren, Gustaf; Rostgaard, Klaus

    2007-01-01

    BACKGROUND: Blood transfusions may influence the recipients' cancer risks both through transmission of biologic agents and by modulation of the immune system. However, cancer occurrence in transfusion recipients remains poorly characterized. METHODS: We used computerized files from Scandinavian...... blood banks to identify a cohort of 888,843 cancer-free recipients transfused after 1968. The recipients were followed from first registered transfusion until the date of death, emigration, cancer diagnosis, or December 31, 2002, whichever came first. Relative risks were expressed as ratios...... of the observed to the expected numbers of cancers, that is, standardized incidence ratios (SIRs), using incidence rates for the general Danish and Swedish populations as a reference. All statistical tests were two-sided. RESULTS: During 5,652,918 person-years of follow-up, 80,990 cancers occurred...

  8. Blood transfusion practices in obstetric anaesthesia

    Directory of Open Access Journals (Sweden)

    Ashok Jadon

    2014-01-01

    Full Text Available Blood transfusion is an essential component of emergency obstetric care and appropriate blood transfusion significantly reduces maternal mortality. Obstetric haemorrhage, especially postpartum haemorrhage, remains one of the major causes of massive haemorrhage and a prime cause of maternal mortality. Blood loss and assessment of its correct requirement are difficult in pregnancy due to physiological changes and comorbid conditions. Many guidelines have been used to assess the requirement and transfusion of blood and its components. Infrastructural, economic, social and religious constraints in blood banking and donation are key issues to formulate practice guidelines. Available current guidelines for transfusion are mostly from the developed world; however, they can be used by developing countries keeping available resources in perspective.

  9. Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line.

    Science.gov (United States)

    Chang, Kee-Lung; Cheng, Hsiao-Ling; Huang, Li-Wen; Hsieh, Bau-Shan; Hu, Yu-Chen; Chih, Tsai-Tung; Shyu, Huey-Wen; Su, Shu-Jem

    2009-04-08

    Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein alone. In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.

  10. mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

    Directory of Open Access Journals (Sweden)

    Rana Baraz

    Full Text Available Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis.

  11. Cell Wall Invertase Promotes Fruit Set under Heat Stress by Suppressing ROS-Independent Cell Death1[OPEN

    Science.gov (United States)

    2016-01-01

    Reduced cell wall invertase (CWIN) activity has been shown to be associated with poor seed and fruit set under abiotic stress. Here, we examined whether genetically increasing native CWIN activity would sustain fruit set under long-term moderate heat stress (LMHS), an important factor limiting crop production, by using transgenic tomato (Solanum lycopersicum) with its CWIN inhibitor gene silenced and focusing on ovaries and fruits at 2 d before and after pollination, respectively. We found that the increase of CWIN activity suppressed LMHS-induced programmed cell death in fruits. Surprisingly, measurement of the contents of H2O2 and malondialdehyde and the activities of a cohort of antioxidant enzymes revealed that the CWIN-mediated inhibition on programmed cell death is exerted in a reactive oxygen species-independent manner. Elevation of CWIN activity sustained Suc import into fruits and increased activities of hexokinase and fructokinase in the ovaries in response to LMHS. Compared to the wild type, the CWIN-elevated transgenic plants exhibited higher transcript levels of heat shock protein genes Hsp90 and Hsp100 in ovaries and HspII17.6 in fruits under LMHS, which corresponded to a lower transcript level of a negative auxin responsive factor IAA9 but a higher expression of the auxin biosynthesis gene ToFZY6 in fruits at 2 d after pollination. Collectively, the data indicate that CWIN enhances fruit set under LMHS through suppression of programmed cell death in a reactive oxygen species-independent manner that could involve enhanced Suc import and catabolism, HSP expression, and auxin response and biosynthesis. PMID:27462084

  12. Effect of red blood cell preservation on blood transfusion in patients with β-thalassemia major of red blood cell%红细胞保存时长对重型β地中海贫血输血效果的影响

    Institute of Scientific and Technical Information of China (English)

    李鹏; 侯振娇

    2016-01-01

    Objective To evaluate the effect of red blood cell preservation on blood transfusion in patients with β-thalassemia major.Methods From February 2010 to December 2015,68 children with β-thalassemia major in 6 hospitals of Kaifeng were selected.The patients were randomly divided into 3 d group and 17 d group according to the number table method,with 34 cases in each group.The patients in the 3 d group accepted the blood preservation after 3 days without white blood cell,and the patients in the 17 d group received blood preservation after 17 days without white blood cell.Concentration of hemoglobin and body weight per kilograms hemoglobin concentration improvement were compared between the two groups before blood transfusion and 24 h,14 days after blood transfusion,and the adverse reactions after transfusion were compared.Results Twenty-four hours after blood transfusion,the hemoglobin concentration in the 3 d group was significantly higher than that in the 17 d group,the difference was significant(P <0.05).Fourteen days after transfusion,there was no significant difference in hemoglobin concentration between the two groups (P > 0.05).Twenty-four hours and 14 days after blood transfusion,body mass blood red protein increasement of body weight per kilograms in the 3 d group was significantly higher than that in the 17 d group,the difference was significant(P < O.05).The hemolytic reaction,rash and non hemolytic febrile transfusion reaction rate of the 3 d group were lower than those of the 17 d group,and the incidence of adverse reactions of 3 d group was significantly lower than that of 17 d group,the difference was significant(P <0.05).Conclusions The effect of preservation of red blood cells with 3 d is significantly higher than that of red blood cells with 17 d,and the adverse reactions of the red blood cells with the preservation of 3 d are significantly lower than those of the red blood cells with 17 d,fresh red blood cells should be used in the process

  13. Recovery of autologous erythrocytes in transfused patients.

    Science.gov (United States)

    Wallas, C H; Tanley, P C; Gorrell, L P

    1980-01-01

    A microcapillary method utilizing phthalate esters or an ultracentrifuge method are both capable of separating autologous from homologous erythrocytes in polytransfused patients. The microcapillary technique which is readily adaptable to blood bank laboratories provides a previously unavailable method for defining blood group antigen typings in transfused patients. Such typings are of vital importance in the laboratory evaluation of transfused patients with multiple or weak blood group antibodies.

  14. [Correlation of hemogram changes during pregnancy of healthy women with postpartum blood transfusion].

    Science.gov (United States)

    Li, Hui; Chen, Lin-Feng; Wang, Shu-Ying; Wang, Yan; Shi, Hong-Mei; Wang, De-Qing

    2012-10-01

    This study was aimed to explore the correlation of hemogram changes during pregnancy of healthy women with postpartum blood transfusion. The outpatient and inpatient information of expectant lying-in women in our hospitals was collected, the route blood test, lever and kidney function and blood coagulation function tests were performed from the 4th to the 10th month of pregnancy. The pregnant women without underlying diseases and non-elderly pregnant women with single fetus were selected as the subjects of study. They were divided into postpartum blood transfusion group and non-blood transfusion group. The white blood cell (WBC) count, hemoglobin (Hb) level, platelet (Plt) count, plateletocrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW) were compared in 2 groups. The results showed that 68 cases out of 450 expectant lying-in women received blood transfusion, among them 30 cases with complete data of puerperal transfusion were taken as blood transfusion group, the 28 cases of non transfusion puerperal as control group. There was no significant difference of hemogram changes between the two groups. However, there was a slight decline in Plt count and Hb level of late pregnant women. What is more, there was no correlation between Plt count change and the PCT, MPV and PDW. It is concluded that the changes of hemogram during pregnancy has no correlation with postpartum hemorrhage and blood transfusion in healthy pregnant women, the Plt count and Hb level of pregnant women slightly decline. Nevertheless, PCT, MPV and PDW are within the normal range.

  15. Factors related to transfusion in very low birthweight infants treated with erythropoietin.

    Science.gov (United States)

    Maier, R. F.; Obladen, M.; Messinger, D.; Wardrop, C. A.

    1996-01-01

    The need for red cell transfusions is reduced but not eliminated by recombinant human erythropoietin (rhEPO) in very low birthweight (VLBW) infants. To detect factors associated with the decision to transfuse VLBW infants during rhEPO treatment and to explain rhEPO 'non-responders', the subgroup of those 120 VLBW infants who were treated with rhEPO 750 IU/kg per week in the second European Multicentre rhEPO Trial was evaluated. Sixty (50%) infants received at least one transfusion during erythropoietin treatment. Transfusion was frequent in infants with extremely low birthweight (79% for 750-999 g), low gestational age (70% for or = 1 ml/kg per day). The prognostic variables birthweight, initial haematocrit, and gestational age were found to be most predictive for transfusion. To improve rhEPO response in VLBW infants, there is a need to minimise diagnostic blood loss, to prevent iron deficiency, and to develop rational criteria for transfusion in preterm infants. PMID:8777681

  16. Polarization of migrating monocytic cells is independent of PI 3-kinase activity.

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    Silvia Volpe

    Full Text Available BACKGROUND: Migration of mammalian cells is a complex cell type and environment specific process. Migrating hematopoietic cells assume a rapid amoeboid like movement when exposed to gradients of chemoattractants. The underlying signaling mechanisms remain controversial with respect to localization and distribution of chemotactic receptors within the plasma membrane and the role of PI 3-kinase activity in cell polarization. METHODOLOGY/PRINCIPAL FINDINGS: We present a novel model for the investigation of human leukocyte migration. Monocytic THP-1 cells transfected with the alpha(2A-adrenoceptor (alpha(2AAR display comparable signal transduction responses, such as calcium mobilization, MAP-kinase activation and chemotaxis, to the noradrenaline homologue UK 14'304 as when stimulated with CCL2, which binds to the endogenous chemokine receptor CCR2. Time-lapse video microscopy reveals that chemotactic receptors remain evenly distributed over the plasma membrane and that their internalization is not required for migration. Measurements of intramolecular fluorescence resonance energy transfer (FRET of alpha(2AAR-YFP/CFP suggest a uniform activation of the receptors over the entire plasma membrane. Nevertheless, PI 3-kinase activation is confined to the leading edge. When reverting the gradient of chemoattractant by moving the dispensing micropipette, polarized monocytes--in contrast to neutrophils--rapidly flip their polarization axis by developing a new leading edge at the previous posterior side. Flipping of the polarization axis is accompanied by re-localization of PI-3-kinase activity to the new leading edge. However, reversal of the polarization axis occurs in the absence of PI 3-kinase activation. CONCLUSIONS/SIGNIFICANCE: Accumulation and internalization of chemotactic receptors at the leading edge is dispensable for cell migration. Furthermore, uniformly distributed receptors allow the cells to rapidly reorient and adapt to changes in the

  17. MUTZ-3 Langerhans cell maturation and CXCL12 independent migration in reconstructed human gingiva.

    Science.gov (United States)

    Kosten, Ilona J; Spiekstra, Sander W; de Gruijl, Tanja D; Gibbs, Susan

    2016-01-01

    Here we describe a reconstructed full thickness human oral mucosa (gingiva) equivalent with integrated Langerhans Cells (GE-LC) and use it to compare LC activation and migration from oral versus skin epithelium. The physiologically representative models consist of differentiated reconstructed epithelium (keratinocytes and Langerhans-like cells derived from the MUTZ-3 cell line) on a fibroblast-populated collagen hydrogel which serves as a lamina propria for gingiva and dermis for skin. Topical exposure of GE-LC and the skin equivalent (SE-LC) to sub-toxic concentrations of the allergens cinnamaldehyde, resorcinol and nickel sulphate, resulted in LC migration out of the epithelia. Neutralizing antibody to CXCL12 blocked allergen-induced LC migration in SE-LC but not in GE-LC. Also, gingival fibroblasts secreted very low amounts of CXCL12 compared to skin fibroblasts even when stimulated with rhTNFα or rhIL-1α. Surprisingly, cinnamaldehyde exposure of GE-LC resulted in an increase in MUTZ-3 LC and CD83 mRNA in the hydrogel but did not result in an increase in CD1a+ cells in the collagen hydrogel (as was observed for SE-LC. These results indicate that in gingiva, upon allergen exposure, MUTZ-3 LC migrate in a CXCL12 independent manner from epithelium-to-lamina propria and in doing so mature become CD1a- and increase CD83+ mRNA. These physiologically relevant in vitro models which not only are human but which also resemble specific tissues, may aid in the identification of factors regulating immune stimulation which in turn will aid the development of therapeutic interventions for allergy and inflammation, anti-cancer vaccines as well as improving diagnostics for skin and oral allergy.

  18. Selection-independent generation of gene knockout mouse embryonic stem cells using zinc-finger nucleases.

    Directory of Open Access Journals (Sweden)

    Anna Osiak

    Full Text Available Gene knockout in murine embryonic stem cells (ESCs has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10(-6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs. Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells.

  19. Selection-independent generation of gene knockout mouse embryonic stem cells using zinc-finger nucleases.

    Science.gov (United States)

    Osiak, Anna; Radecke, Frank; Guhl, Eva; Radecke, Sarah; Dannemann, Nadine; Lütge, Fabienne; Glage, Silke; Rudolph, Cornelia; Cantz, Tobias; Schwarz, Klaus; Heilbronn, Regine; Cathomen, Toni

    2011-01-01

    Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10(-6). In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells.

  20. The best transfusion time of autologous cytokine-induced killer cell for malignant tumor patients accepted adoptive immunotherapy%自体CIK过继免疫治疗恶性肿瘤的最佳输注时间

    Institute of Scientific and Technical Information of China (English)

    邓海峰; 吴昌平; 蒋敬庭; 陆明洋; 徐斌; 郑晓; 李敏; 刘检; 周怡; 孙青; 石红兵

    2011-01-01

    目的 研究恶性肿瘤患者自体细胞因子诱导的杀伤细胞(CIK)的免疫表型与细胞毒活性的变化规律,探讨肿瘤患者CIK过继免疫治疗输注的最佳时间.方法 采集40例恶性肿瘤患者外周血单个核细胞(PBMC),由IFN-γ、rhIL-1 α、rhIL-2等细胞因子和CD3单克隆抗体体外诱导培养成CIK.用流式细胞术动态监测免疫表型,MTT法分析细胞毒活性.结果 随着诱导时间的延长,PBMC中CD3+、CD3+CD8+、CD3+ CD56+表型细胞所占比例呈上升趋势.CD3+ CD4+细胞在7d达到峰值,随后缓慢下降.CD25+细胞在培养的早期(3~7 d)即达峰值,7~14 d缓慢下降,14~21 d快速下降.HLA-DR+细胞在0~14d处于上升期,14 d达峰值后快速下降.成熟CIK细胞毒活性[(52.49±7.70)%]较未活化的PBMC[( 7.02±2.00)%]显著增高(P<0.01).结论 14 d左右能诱导出典型的CIK,CD3+ CD56+细胞处于对数生长期.确立自体CIK过继免疫治疗恶性肿瘤的最佳输注时间为第14天.%Objective To investigate the change rule of immunophenotype and cytotoxic activity of autologous cytokine-induced killer (CIK) cells, and explore the best transfusion time of CIK cell during the adoptive iramunotherapy for malignant tumor patients. Methods Peripheral blood mononuclear cells (PBMC) of 40 patients with malignant tumors were collected and induced into CIK cells in vitro by incubation with several kinds of cytokines including IFN-γ, rhIL-lα, rhIL-2 and CD3 monoclonal antibody (McAb). Dynamic state of immunophenotype of CIK cells was determined by flow cytometry, and the cytotoxicity of CIK cells was analyzed by MTT method. Results Following induction with mononuclear cells, the number of cells with phenotype of CD3 + , CD3 + CD8 + and CD3 + CD56+ showed upward trend. The number of CD3 + CD4+ cells Teached the peak value after 7 days, and then decreased slowly. The CD25 cells reached the peak value in earlier phase (after induction of 3-7 days) , and decreased slowly

  1. B cells regulate CD4+ T cell responses to papain following B cell receptor-independent papain uptake.

    Science.gov (United States)

    Dwyer, Daniel F; Woodruff, Matthew C; Carroll, Michael C; Austen, K Frank; Gurish, Michael F

    2014-07-15

    Papain, a cysteine protease allergen with inherent adjuvant activity, induces potent IL-4 expression by T cells in the popliteal lymph nodes of mice following footpad immunization. In this study, we identify a novel, non-BCR-mediated capacity for B cells to rapidly bind and internalize papain. B cells subsequently regulate the adaptive immune response by enhancing ICOS expression on CD4(+) T cells and amplifying Th2 and follicular helper T cell induction. Ab blockade of ICOS ligand, expressed by popliteal lymph node B cells, but not dendritic cells, at the peak of the response inhibits IL-4 responses in wild-type mice but not B cell-deficient mice. Thus, B cells play a critical role in amplifying adjuvant-dependent Th2 polarization following noncanonical acquisition and internalization of the cysteine protease papain.

  2. Efficacy of fresh packed red blood transfusion in organophosphate poisoning

    Science.gov (United States)

    Bao, Hang-xing; Tong, Pei-jian; Li, Cai-xia; Du, Jing; Chen, Bing-yu; Huang, Zhi-hui; Wang, Ying

    2017-01-01

    Abstract The mortality rate caused by organophosphate (OP) poisoning is still high, even the standard treatment such as atropine and oxime improves a lot. To search for alternative therapies, this study was aimed to investigate the effects of packed red blood cell (RBC) transfusion in acute OP poisoning, and compare the therapeutic effects of RBCs at different storage times. Patients diagnosed with OP poisoning were included in this prospective study. Fresh RBCs (packed RBCs stored less than 10 days) and longer-storage RBCs (stored more than 10 days but less than 35 days) were randomly transfused or not into OP poisoning patients. Cholinesterase (ChE) levels in blood, atropine usage and durations, pralidoxime durations were measured. We found that both fresh and longer-storage RBCs (200–400 mL) significantly increased blood ChE levels 6 hours after transfusion, shortened the duration for ChE recovery and length of hospital stay, and reduced the usage of atropine and pralidoxime. In addition, fresh RBCs demonstrated stronger therapeutic effects than longer-storage RBCs. Packed RBCs might be an alternative approach in patients with OP poisoning, especially during early stages. PMID:28296779

  3. Infection of XC cells by MLVs and Ebola virus is endosome-dependent but acidification-independent.

    Science.gov (United States)

    Kamiyama, Haruka; Kakoki, Katsura; Yoshii, Hiroaki; Iwao, Masatomo; Igawa, Tsukasa; Sakai, Hideki; Hayashi, Hideki; Matsuyama, Toshifumi; Yamamoto, Naoki; Kubo, Yoshinao

    2011-01-01

    Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.

  4. 输注红细胞悬液前、后患者凝血功能检测结果对比研究%Comparison of Coagulation Function Test Results in Patients with Transfusion of Red Blood Cell Suspension

    Institute of Scientific and Technical Information of China (English)

    杨莉萍

    2015-01-01

    目的研究总结输注红细胞悬液前、后患者凝血功能检测结果的变化,为临床输血治疗提供可参考依据。方法抽取我院住院部2013年1月~2014年1月收治手术输血患者79例,为研究对象。所有患者均自愿参与研究,签署知情同意书。统计所有研究对象输注红细胞悬液前、后实验室检测凝血功能结果。结果输注红细胞悬液后,患者各项指标均优于输注前,<0.05。结论输注红细胞悬液会导致患者体内凝血功能降低,输注红细胞悬液患者需密切监控凝血功能,补充血浆和血小板等成分,防止发生输血危险事件。%Objective To study the summary of transfusion of red blood cel suspension before and after the change of the blood coagulation function in patients with test results,and provide reference basis for clinical blood transfusion therapy.Methods To extract the inpatient in January 2013~January 2014 surgical patients,79 cases of blood transfusion,as the research object.Al of the patients are voluntary study,signed informed consent.Statistics al the object of study before the transfusion of red blood cel suspension,laboratory tests after coagulation function results.Results After transfusion of red blood cel suspension,the indicators are bet er than the before infusion, <0.05.Conclusion The transfusion of red blood cel suspension can reduce patient blood coagulation function and transfusion of red blood cel suspension need to closely monitorpatients with blood coagulation function,plasma and platelet composition such as supplement,prevent blood transfusion risk events.

  5. A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis

    Science.gov (United States)

    Kollmann, Karoline; Heller, Gerwin; Schneckenleithner, Christine; Warsch, Wolfgang; Scheicher, Ruth; Ott, Rene G.; Schäfer, Markus; Fajmann, Sabine; Schlederer, Michaela; Schiefer, Ana-Iris; Reichart, Ursula; Mayerhofer, Matthias; Hoeller, Christoph; Zöchbauer-Müller, Sabine; Kerjaschki, Dontscho; Bock, Christoph; Kenner, Lukas; Hoefler, Gerald; Freissmuth, Michael; Green, Anthony R.; Moriggl, Richard; Busslinger, Meinrad; Malumbres, Marcos; Sexl, Veronika

    2013-01-01

    Summary In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6’s kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6’s central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a. PMID:23948297

  6. Investigation of low temperature solid oxide fuel cells for air-independent UUV applications

    Science.gov (United States)

    Moton, Jennie Mariko

    Unmanned underwater vehicles (UUVs) will benefit greatly from high energy density (> 500 Wh/L) power systems utilizing high-energy-density fuels and air-independent oxidizers. Current battery-based systems have limited energy densities (electrolytes with operating temperatures of 650°C and lower may operate in the unique environments of a promising UUV power plant. The plant would contain a H 2O2 decomposition reactor to supply humidified O2 to the SOFC cathode and exothermic aluminum/H2O combustor to provide heated humidified H2 fuel to the anode. To characterize low-temperature SOFC performance with these unique O2 and H2 source, SOFC button cells based on nickel/GDC (Gd0.1Ce0.9O 1.95) anodes, GDC electrolytes, and lanthanum strontium cobalt ferrite (La0.6Sr0.4Co0.2Fe0.8O3-δ or LSCF)/GDC cathodes were fabricated and tested for performance and stability with humidity on both the anode and the cathode. Cells were also tested with various reactant concentrations of H2 and O2 to simulate gas depletion down the channel of an SOFC stack. Results showed that anode performance depended primarily on fuel concentration and less on the concentration of the associated increase in product H2O. O 2 depletion with humidified cathode flows also caused significant loss in cell current density at a given voltage. With the humidified flows in either the anode or cathode, stability tests of the button cells at 650 °C showed stable voltage is maintained at low operating current (0.17 A/cm2) at up to 50 % by mole H2O, but at higher current densities (0.34 A/cm2), irreversible voltage degradation occurred at rates of 0.8-3.7 mV/hour depending on exposure time. From these button cell results, estimated average current densities over the length of a low-temperature SOFC stack were estimated and used to size a UUV power system based on Al/H 2O oxidation for fuel and H2O2 decomposition for O2. The resulting system design suggested that energy densities above 300 Wh/L may be achieved at

  7. An Analysis of and Recommendations for the Peruvian Blood Collection and Transfusion System

    Science.gov (United States)

    George, Paul E; Vidal, Julio; Garcia, Patricia J

    2016-01-01

    Background Peru experienced a crisis in its blood collection and supply system in the mid-2000s, as contaminated blood led to several transfusion-transmitted infections (TTI), occurring in the backdrop of extremely low voluntary donation rates and a national blood supply shortage. Thus, the Peruvian Ministry of Health (MINSA) implemented a national investigation on the safety and quality of the Peruvian blood collection/transfusion network. Methods Every Peruvian blood bank was evaluated by MINSA from 2007–2008. These evaluations consisted of an update of the national registry of blood banks and visits to each blood bank from MINSA oversight teams. Information was collected on the condition of the blood bank personnel, equipment, supplies, and practices. Further, previously-collected blood at each blood bank was randomly selected and screened for TTI-causing pathogens. Results Uncovered in this investigation was a fragmented, under-equipped, and poorly-staffed blood collection and transfusion network, consisting of 241 independent blood banks and resulting in suboptimal allocation of resources. Further, blood with evidence of TTI-causing pathogens (including Hepatitis B, Hepatitis C, and syphilis) and set for transfusion was discovered at three separate blood banks as part of the random screening process. Conclusion Using the successful reorganizations of national blood supply systems in other Latin American countries as examples, Peru would be well-served to form large, high-volume, regional blood collection and transfusion centers, responsible for blood collection and screening for the entire country. The small, separate blood banks would then be transformed into a network of blood transfusion centers, not responsible for blood collection. This reorganization would allow Peru to better utilize its resources, standardize the blood collection and transfusion process, and increase voluntary donation, resulting in a safer, more abundant national blood product.

  8. Predictive factors for perioperative blood transfusion in surgeries for correction of idiopathic, neuromuscular or congenital scoliosis

    Directory of Open Access Journals (Sweden)

    Alexandre Fogaça Cristante

    2014-12-01

    Full Text Available OBJECTIVE: To evaluate the association of clinical and demographic variables in patients requiring blood transfusion during elective surgery to treat scoliosis with the aim of identifying markers predictive of the need for blood transfusion. METHODS: Based on the review of medical charts at a public university hospital, this retrospective study evaluated whether the following variables were associated with the need for red blood cell transfusion (measured by the number of packs used during scoliosis surgery: scoliotic angle, extent of arthrodesis (number of fused levels, sex of the patient, surgery duration and type of scoliosis (neuromuscular, congenital or idiopathic. RESULTS: Of the 94 patients evaluated in a 55-month period, none required a massive blood transfusion (most patients needed less than two red blood cell packs. The number of packs was not significantly associated with sex or type of scoliosis. The extent of arthrodesis (r = 0.103, surgery duration (r = 0.144 and scoliotic angle (r = 0.004 were weakly correlated with the need for blood transfusion. Linear regression analysis showed an association between the number of spine levels submitted to arthrodesis and the volume of blood used in transfusions (p = 0.001. CONCLUSION: This study did not reveal any evidence of a significant association between the need for red blood cell transfusion and scoliotic angle, sex or surgery duration in scoliosis correction surgery. Submission of more spinal levels to arthrodesis was associated with the use of a greater number of blood packs.

  9. Transfusion of CXCR4-primed endothelial progenitor cells reduces cerebral ischemic damage and promotes repair in db/db diabetic mice.

    Directory of Open Access Journals (Sweden)

    Ji Chen

    Full Text Available This study investigated the role of stromal cell-derived factor-1α (SDF-1α/CXC chemokine receptor 4 (CXCR4 axis in brain and endothelial progenitor cells (EPCs, and explored the efficacy of CXCR4 primed EPCs in treating ischemic stroke in diabetes. The db/db diabetic and db/+ mice were used in this study. Levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were measured. Brain SDF-1α and CXCR4 expression were quantified at basal and after middle cerebral artery occlusion (MCAO. In in vitro study, EPCs were transfected with adenovirus carrying null (Ad-null or CXCR4 (Ad-CXCR4 followed with high glucose (HG treatment for 4 days. For pathway block experiments, cells were pre-incubated with PI3K inhibitor or nitric oxide synthase (NOS inhibitor for two hours. The CXCR4 expression, function and apoptosis of EPCs were determined. The p-Akt/Akt and p-eNOS/eNOS expression in EPCs were also measured. In in vivo study, EPCs transfected with Ad-null or Ad-CXCR4 were infused into mice via tail vein. On day 2 and 7, the cerebral blood flow, neurologic deficit score, infarct volume, cerebral microvascular density, angiogenesis and neurogenesis were determined. We found: 1 The levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were decreased in db/db mice; 2 The basal level of SDF-1α and MCAO-induced up-regulation of SDF-1α/CXCR4 axis were reduced in the brain of db/db mice; 3 Ad-CXCR4 transfection increased CXCR4 expression in EPCs and enhanced EPC colonic forming capacity; 4 Ad-CXCR4 transfection prevented EPCs from HG-induced dysfunction (migration and tube formation and apoptosis via activation of PI3K/Akt/eNOS signal pathway; 4 Ad-CXCR4 transfection enhanced the efficacy of EPC infusion in attenuating infarct volume and promoting angiogenesis and neurogenesis. Our data suggest that Ad-CXCR4 primed EPCs have better therapeutic effects for ischemia stroke in diabetes than unmodified EPCs do.

  10. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Davis Rodney

    2006-07-01

    Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

  11. Blood transfusion : Transfusion-related acute lung injury: back to basics

    NARCIS (Netherlands)

    Peters, A.L.

    2017-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening disease affecting the lungs. TRALI can develop within 6 hours after transfusion and almost all patients with TRALI require mechanical ventilation at the intensive care department. Nevertheless up to 40% of patients do not recover fr

  12. Use of an Immobilized Monoclonal Antibody to Examine Integrin &agr;5&bgr;1 Signaling Independent of Cell Spreading

    Directory of Open Access Journals (Sweden)

    Bao Wenjie

    2002-01-01

    Full Text Available Cell attachment to the extracellular matrix (ECM engages integrin signaling into the cell, but part of the signaling response also stem from cell spreading (3. To analyze specific integrin signaling-mediated responses independent of cell spreading, we developed a method engaging integrin signaling by use of an immobilized anti-integrin monoclonal antibody (mab directed against the fibronectin (FN receptor integrin &agr;5&bgr;1. ECV 304 cells were plated onto FN or immobilized mab JBS5 (anti-integrin &agr;5&bgr;1 or onto poly-L-lysin (P-L-L, which mediates integrin-independent attachment. Cells attached and spread on FN, while cells on JBS5 or P-L-L attached but did not spread. Importantly, plating onto FN or mab JBS5 gave rise to identical integrin-induced responses, including a down-regulation of the cyclin-dependent kinase (Cdk2 inhibitors p21CIP1 and p27KIP1, while attachment to P-L-L did not. We conclude that engagement of the FN-receptor integrin &agr;5&bgr;1 induces integrin signaling regulating the Cdk2-inhibitors independent of cell spreading and present a method for how integrin signaling can be analyzed separate from the effects of cell spreading.

  13. The alpha1-adrenoceptor antagonist terazosin induces prostate cancer cell death through a p53 and Rb independent pathway.

    Science.gov (United States)

    Xu, Kexin; Wang, Xianghong; Ling, Patrick M T; Tsao, S W; Wong, Y C

    2003-01-01

    Prostate cancer is the second leading cause of cancer-related death in men. Treatment failure in prostate cancer is usually due to the development of androgen independence and resistance to chemotherapeutic drugs at an advanced stage. Recently, it was reported that the alpha1-adrenoceptor antagonist terazosin was able to inhibit prostate cancer cell growth and indicated that it may have an implication in the treatment of prostate cancer. The aim of the present study was to investigate the mechanisms involved in terazosin-induced prostate cancer cell death using two androgen-independent cell lines, PC-3 and DU145. Our results showed that terazosin inhibited not only prostate cancer cell growth but also colony forming ability, which is the main target of chemotherapy. We also found that the sensitivity of these cells to terazosin was not affected by the presence of either functional p53 or Rb, suggesting that the terazosin-induced cell death was independent of p53 and Rb. However, the terazosin-induced cell death was associated with G1 phase cell cycle arrest and up-regulation of p27KIP1. In addition, up-regulation of Bax and down-regulation of Bcl-2 was also observed indicating that these two apoptotic regulators may play important roles in terazosin-mediated cell death pathway. Our results provide evidence for the first time that terazosin may have a therapeutic potential in the treatment of advanced prostate cancer.

  14. Mechanisms of Alloimmunization and Subsequent Bone Marrow Transplantation Rejection Induced by Platelet Transfusion in a Murine Model

    Science.gov (United States)

    Patel, Seema R; Smith, Nicole H; Kapp, Linda; Zimring, James C

    2015-01-01

    For many non-malignant hematological disorders, HLA-matched bone marrow transplantation (BMT) is curative. However, due to lack of neoplasia, the toxicity of stringent conditioning regimens is difficult to justify, and reduced-intensity conditioning is used. Unfortunately, current reduced-intensity regimens have high rates of BMT rejection. We have recently reported in a murine model that mHAs on transfused platelet products induce subsequent BMT rejection. Most non-malignant hematological disorders require transfusion support prior to BMT and the rate of BMT rejection in humans correlates to the number of transfusions given. Herein, we perform a mechanistic analysis of platelet transfusion induced BMT rejection and report that unlike exposure to alloantigens during transplantation, platelet transfusion primes alloimmunity but does not stimulate full effector function. Subsequent BMT is itself an additional and distinct immunizing event, which does not induce rejection without antecedent priming from transfusion. Both CD4+ and CD8+ T cells are required for priming during platelet transfusion, but only CD8+ T cells are required for BMT rejection. In neither case are antibodies required for rejection to occur. PMID:22300526

  15. [The 2013 Seville Consensus Document on alternatives to allogenic blood transfusion. An update on the Seville Document].

    Science.gov (United States)

    Leal-Noval, S R; Muñoz, M; Asuero, M; Contreras, E; García-Erce, J A; Llau, J V; Moral, V; Páramo, J A; Quintana, M; Basora, M; Bautista-Paloma, F J; Bisbe, E; Bóveda, J L; Castillo-Muñoz, A; Colomina, M J; Fernández, C; Fernández-Mondéjar, E; Ferrándiz, C; García de Lorenzo, A; Gomar, C; Gómez-Luque, A; Izuel, M; Jiménez-Yuste, V; López-Briz, E; López-Fernández, M L; Martín-Conde, J A; Montoro-Ronsano, B; Paniagua, C; Romero-Garrido, J A; Ruiz, J C; Salinas-Argente, R; Sánchez, C; Torrabadella, P; Arellano, V; Candela, A; Fernández, J A; Fernández-Hinojosa, E; Puppo, A

    2013-05-01

    Since allogeneic blood transfusion (ABT) is not harmless, multiple alternatives to ABT (AABT) have emerged, though there is great variability in their indications and appropriate use. This variability results from the interaction of a number of factors, including the specialty of the physician, knowledge and preferences, the degree of anemia, transfusion policy, and AABT availability. Since AABTs are not harmless and may not meet cost-effectiveness criteria, such variability is unacceptable. The Spanish Societies of Anesthesiology (SEDAR), Hematology and Hemotherapy (SEHH), Hospital Pharmacy (SEFH), Critical Care Medicine (SEMICYUC), Thrombosis and Hemostasis (SETH) and Blood Transfusion (SETS) have developed a Consensus Document for the proper use of AABTs. A panel of experts convened by these 6 Societies have conducted a systematic review of the medical literature and have developed the 2013 Seville Consensus Document on Alternatives to Allogeneic Blood Transfusion, which only considers those AABT aimed at decreasing the transfusion of packed red cells. AABTs are defined as any pharmacological or non-pharmacological measure aimed at decreasing the transfusion of red blood cell concentrates, while preserving patient safety. For each AABT, the main question formulated, positively or negatively, is: « Does this particular AABT reduce the transfusion rate or not?» All the recommendations on the use of AABTs were formulated according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) methodology.

  16. Platelet transfusion refractoriness attributable to HLA antibodies produced by donor-derived cells after allogeneic bone marrow transplantation from one HLA-antigen-mismatched mother.

    Science.gov (United States)

    Hatakeyama, Naoki; Hori, Tsukasa; Yamamoto, Masaki; Inazawa, Natsuko; Iesato, Kotoe; Miyazaki, Toru; Ikeda, Hisami; Tsutsumi, Hiroyuki; Suzuki, Nobuhiro

    2011-12-01

    PTR is a serious problem in patients being treated for hematologic disorders. Two patients with acute leukemia developed PTR after allogeneic BMT from one HLA-antigen-mismatched mother attributable to HLA antibodies, which could not be detected in their serum before BMT. HLA antibodies, whose specificity resembled that of each patient, were detected in each donor's serum. Each donor had probably been immunized during pregnancy by their partner's HLA antigens expressed by the fetus, consequently, transplanted donor-derived cells provoked HLA antibodies in each recipient early after BMT, and those HLA antibodies induced PTR. If the mothers are selected as donors for their children, they should be tested for the presence of HLA antibodies.

  17. Retention of prolyl hydroxylase PHD2 in the cytoplasm prevents PHD2-induced anchorage-independent carcinoma cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Jokilehto, Terhi [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Turku Graduate School of Biomedical Sciences, Turku (Finland); Hoegel, Heidi [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Heikkinen, Pekka [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Turku Graduate School of Biomedical Sciences, Turku (Finland); Rantanen, Krista [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Elenius, Klaus [Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku (Finland); Department of Medical Biochemistry and Genetics, University of Turku and Turku University Hospital, Turku (Finland); Sundstroem, Jari [Department of Pathology, University of Turku and Turku University Hospital, Turku (Finland); Jaakkola, Panu M. [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku (Finland)

    2010-04-15

    Cellular oxygen tension is sensed by a family of prolyl hydroxylases (PHD1-3) that regulate the degradation of hypoxia-inducible factors (HIF-1{alpha} and -2{alpha}). The PHD2 isoform is considered as the main downregulator of HIF in normoxia. Our previous results have shown that nuclear translocation of PHD2 associates with poorly differentiated tumor phenotype implying that nuclear PHD2 expression is advantageous for tumor growth. Here we show that a pool of PHD2 is shuttled between the nucleus and the cytoplasm. In line with this, accumulation of wild type PHD2 in the nucleus was detected in human colon adenocarcinomas and in cultured carcinoma cells. The PHD2 isoforms showing high nuclear expression increased anchorage-independent carcinoma cell growth. However, retention of PHD2 in the cytoplasm inhibited the anchorage-independent cell growth. A region that inhibits the nuclear localization of PHD2 was identified and the deletion of the region promoted anchorage-independent growth of carcinoma cells. Finally, the cytoplasmic PHD2, as compared with the nuclear PHD2, less efficiently downregulated HIF expression. Forced HIF-1{alpha} or -2{alpha} expression decreased and attenuation of HIF expression increased the anchorage-independent cell growth. However, hydroxylase-inactivating mutations in PHD2 had no effect on cell growth. The data imply that nuclear PHD2 localization promotes malignant cancer phenotype.

  18. Rapid activation of Rac GTPase in living cells by force is independent of Src.

    Directory of Open Access Journals (Sweden)

    Yeh-Chuin Poh

    Full Text Available It is well known that mechanical forces are crucial in regulating functions of every tissue and organ in a human body. However, it remains unclear how mechanical forces are transduced into biochemical activities and biological responses at the cellular and molecular level. Using the magnetic twisting cytometry technique, we applied local mechanical stresses to living human airway smooth muscle cells with a magnetic bead bound to the cell surface via transmembrane adhesion molecule integrins. The temporal and spatial activation of Rac, a small guanosine triphosphatase, was quantified using a fluorescent resonance energy transfer (FRET method that measures changes in Rac activity in response to mechanical stresses by quantifying intensity ratios of ECFP (enhanced cyan fluorescent protein as a donor and YPet (a variant yellow fluorescent protein as an acceptor of the Rac biosensor. The applied stress induced rapid activation (less than 300 ms of Rac at the cell periphery. In contrast, platelet derived growth factor (PDGF induced Rac activation at a much later time (>30 sec. There was no stress-induced Rac activation when a mutant form of the Rac biosensor (RacN17 was transfected or when the magnetic bead was coated with transferrin or with poly-L-lysine. It is known that PDGF-induced Rac activation depends on Src activity. Surprisingly, pre-treatment of the cells with specific Src inhibitor PP1 or knocking-out Src gene had no effects on stress-induced Rac activation. In addition, eliminating lipid rafts through extraction of cholesterol from the plasma membrane did not prevent stress-induced Rac activation, suggesting a raft-independent mechanism in governing the Rac activation upon mechanical stimulation. Further evidence indicates that Rac activation by stress depends on the magnitudes of the applied stress and cytoskeletal integrity. Our results suggest that Rac activation by mechanical forces is rapid, direct and does not depend on Src

  19. Osteogenic Differentiation of Adipose-Derived Stem Cells Is Hypoxia-Inducible Factor-1 Independent

    Science.gov (United States)

    Sahai, Suchit; Williams, Amanda; Skiles, Matthew L.

    2013-01-01

    Tissue engineering is a promising approach to repair critical-size defects in bone. Damage to vasculature at the defect site can create a lower O2 environment compared with healthy bone. Local O2 levels influence stem cell behavior, as O2 is not only a nutrient, but also a signaling molecule. The hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates a wide range of O2-related genes and its contribution in bone repair/formation is an important area that can be exploited. In this study, we examined the effect of low O2 environments (1% and 2% O2) on the osteogenic differentiation of adipose-derived stem cells in both two-dimensional (2-D) and three-dimensional (3-D) culture systems. To determine the role of HIF-1 in the differentiation process, an inhibitor was used to block the HIF-1 activity. The samples were examined for osteogenesis markers as measured by quantification of the alkaline phosphatase (ALP) activity, mineral deposition, and expression of osteonectin (ON) and osteopontin (OPN). Results show a downregulation of the osteogenic markers (ALP activity, mineralization, ON, OPN) in both 1% and 2% O2 when compared to 20% O2 in both 2-D and 3-D culture. Vascular endothelial growth factor secretion over 28 days was significantly higher in low O2 environments and HIF-1 inhibition reduced this effect. The inhibition of the HIF-1 activity did not have a significant impact on the expression of the osteogenic markers, suggesting HIF-1-independent inhibition of osteogenic differentiation in hypoxic conditions. PMID:23394201

  20. LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity.

    Directory of Open Access Journals (Sweden)

    Roberta Bertelli

    Full Text Available Immunosuppressive regulatory T cells (Tregs have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna and/or drug induced (Adriamycin nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg was given as single shot in C57BL/6, p2rx7⁻/⁻ and Foxp3EGFP; free IL-2 (18.000 U or, in alternative, IL-2 coupled with JES6-1 mAb (IL-2/anti-IL-2 were injected before LPS. Peripheral and tissue Tregs/total CD4+ cell ratio, urinary parameters and renal histology were evaluated for 15 days. IL-2 administration to wild type mice had no effect on peripheral Tregs number, whereas a significant increase was induced by the IL-2/anti-IL-2 immunocomplex after 5 days. Spleen and lymph nodes Tregs were comparably increased. In p2rx7⁻/⁻ mice, IL-2/anti-IL-2 treatment resulted in increase of peripheral Tregs but did not modify the spleen and lymph nodes quota. LPS induced comparable and transient proteinuria in both wild type and p2rx7⁻/⁻ mice. Proteinuria was inhibited by co-infusion of human IL-2, with reduction at each phase of the disease (24 -48 and 72 hours whereas IL-2/anti-IL-2 produced weaker effects. In all mice (wild type and p2rx7⁻/⁻ and irrespective of treatment (IL-2, IL-2/anti-IL-2, LPS was associated with progressive signs of renal pathologic involvement resulting in glomerulosclerosis. In conclusion, IL-2 plays a transient protective effect on proteinuria induced by LPS independent of circulating or tissue Tregs but does not modify the outcome of renal degenerative renal lesions.

  1. Troglitazone inhibits cell proliferation by attenuation of epidermal growth factor receptor signaling independent of peroxisome proliferator-activated receptor γ

    Institute of Scientific and Technical Information of China (English)

    Xiaoqi Li; Xuanming Yang; Youli Xu; Xuejun Jiang; Xin Li; Fajun Nan; Hong Tang

    2009-01-01

    Peroxisome proliferator-activated receptors (PPAR) belong to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. Recent results have shown that agonists of PPARy, such as troglitazone (TGZ), can inhibit cell proliferation and promote cell differentiation independent of PPARγ. In the present study, we provide evidence that TGZ may bind directly to EGFR and trigger its signaling and internalization independent of PPARγ. Detailed studies revealed that prolonged incubation with TGZ effectively attenuated EGFR signaling by target-ing the receptor to the endo-lysosomal degradation machinery. Although the extracellular signal-regulated kinase-signaling pathway was transiently activated by TGZ in EGFR overexpressing cancer cells, inhibition of EGF-induced Akt phosphorylation most likely accounted for the growth arrest of tumor cells caused by TGZ at pharmacologically achievable concentrations. Therefore, we have provided a new line of evidence indicating that TGZ inhibits cell pro-liferation by promoting EGFR degradation and attenuating Akt phosphorylation.

  2. Propylthiouracil, independent of its antithyroid effect, promotes vascular smooth muscle cells differentiation via PTEN induction.

    Science.gov (United States)

    Chen, Wei-Jan; Pang, Jong-Hwei S; Lin, Kwang-Huei; Lee, Dany-Young; Hsu, Lung-An; Kuo, Chi-Tai

    2010-01-01

    Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have an antiatherosclerotic effect. The aim of this study is to determine the impact of PTU on phenotypic modulation of vascular smooth muscle cells (VSMCs), as phenotypic modulation may contribute to the growth of atherosclerotic lesions and neointimal formation after arterial injury. Propylthiouracil reduced neointimal formation in balloon-injured rat carotid arteries. In vitro, PTU may convert VSMCs from a serum-induced dedifferentiation state to a differentiated state, as indicated by a spindle-shaped morphology and an increase in the expression of SMC differentiation marker contractile proteins, including calponin and smooth muscle (SM)-myosin heavy chain (SM-MHC). Transient transfection studies in VSMCs demonstrated that PTU induced the activity of SMC marker genes (calponin and SM-MHC) promoters, indicating that PTU up-regulates these genes expression predominantly at the transcriptional level. Furthermore, PTU enhanced the expression of PTEN and inhibition of PTEN by siRNA knockdown blocked PTU-induced activation of contractile proteins expression and promoter activity. In the rat carotid injury model, PTU reversed the down-regulation of contractile proteins and up-regulated PTEN in the neointima induced by balloon injury. Propylthiouracil promotes VSMC differentiation, at lest in part, via induction of the PTEN-mediated pathway. These findings suggest a possible mechanism by which PTU may contribute to its beneficial effects on atherogenesis and neointimal formation after arterial injury.

  3. Influence of cations and anions on the induction of cell density-independent luminescence in Photorhabdus luminescens.

    Science.gov (United States)

    Tabei, Yosuke; Ogawa, Akane; Era, Mariko; Ninomiya, Junko; Morita, Hiroshi

    2013-03-01

    Bioluminescence is emitted by various living organisms, including bacteria. While the induction mechanism in marine luminescent bacteria, such as Vibrio fischeri and V. harveyi, has been well characterized, this mechanism has not been studied in detail in the non-marine luminescent bacterium Photorhabdus luminescens. Therefore, we investigated the effect of cations and anions on the induction of luminescence by P. luminescens. Cultivation of cells in an inorganic salts solution (ISS) containing KCl, CaCl2 , MgCl2 , NaHCO3 , and MgSO4 resulted in a rapid increase in luminescence intensity. Moreover, the induction of luminescence in the ISS medium was not dependent on cell density, since cell densities remained unchanged during 48 h. Furthermore, we found that compounds containing K(+) , Mg(2+) , and HCO3(-) were necessary to induce cell density-independent luminescence. The intensity of luminescence per cell cultured in medium containing KCl, MgCl2 , and NaHCO3 was approximately 100-fold higher than that cultured in NB. In contrast, when cells actively grew in normal growth condition, the intensity of luminescence per cell was not increased even in the presence of K(+) , Mg(2+) , and HCO3(-) . Thus, these results suggest that the luminescence of P. luminescens is regulated by 2 independent cell density-dependent and -independent mechanisms.

  4. Transfusion and blood donation in comic strips.

    Science.gov (United States)

    Lefrère, Jean-Jacques; Danic, Bruno

    2013-07-01

    The representation of blood transfusion and donation of blood in the comic strip has never been studied. The comic strip, which is a relatively recent art, emerged in the 19th century before becoming a mass medium during the 20th century. We have sought, by calling on collectors and using the resources of Internet, comic strips devoted, wholly or in part, to the themes of transfusion and blood donation. We present some of them here in chronologic order, indicating the title, country of origin, year of publication, and names of authors. The theme of the superhero using transfusion to transmit his virtues or his powers is repeated throughout the 20th century in North American comic strips. More recently, comic strips have been conceived from the outset with a promotional aim. They perpetuate positive images and are directed toward a young readership, wielding humor to reduce the fear of venipuncture. Few comic strips denounce the abuse of the commercialization of products derived from the human body. The image of transfusion and blood donation given by the comic strips is not to be underestimated because their readership is primarily children, some of whom will become blood donors. Furthermore, if some readers are transfused during their lives, the impact of a memory more or less conscious of these childhood readings may resurface, both in hopes and in fears.

  5. Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Yukihiro Nishikawa

    Full Text Available Withaferin A (WA, a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD. WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L. Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death.

  6. Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Liliana, E-mail: lilianam87@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Araújo, Isabel, E-mail: isa.araujo013@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Costa, Tito, E-mail: tito.fmup16@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Correia-Branco, Ana, E-mail: ana.clmc.branco@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Faria, Ana, E-mail: anafaria@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Chemistry Investigation Centre (CIQ), Faculty of Sciences of University of Porto, Rua Campo Alegre, 4169-007 Porto (Portugal); Faculty of Nutrition and Food Sciences of University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Martel, Fátima, E-mail: fmartel@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Keating, Elisa, E-mail: keating@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal)

    2013-07-15

    In this study we characterized {sup 3}H-2-deoxy-D-glucose ({sup 3}H -DG) uptake by the estrogen receptor (ER)-positive MCF7 and the ER-negative MDA-MB-231 human breast cancer cell lines and investigated the effect of quercetin (QUE) and epigallocatechin gallate (EGCG) upon {sup 3}H-DG uptake, glucose metabolism and cell viability and proliferation. In both MCF7 and MDA-MB-231 cells {sup 3}H-DG uptake was (a) time-dependent, (b) saturable with similar capacity (V{sub max}) and affinity (K{sub m}), (c) potently inhibited by cytochalasin B, an inhibitor of the facilitative glucose transporters (GLUT), (d) sodium-independent and (e) slightly insulin-stimulated. This suggests that {sup 3}H-DG uptake by both cell types is mediated by members of the GLUT family, including the insulin-responsive GLUT4 or GLUT12, while being independent of the sodium-dependent glucose transporter (SGLT1). QUE and EGCG markedly and concentration-dependently inhibited {sup 3}H-DG uptake by MCF7 and by MDA-MB-231 cells, and both compounds blocked lactate production by MCF7 cells. Additionally, a 4 h-treatment with QUE or EGCG decreased MCF7 cell viability and proliferation, an effect that was more potent when glucose was available in the extracellular medium. Our results implicate QUE and EGCG as metabolic antagonists in breast cancer cells, independently of estrogen signalling, and suggest that these flavonoids could serve as therapeutic agents/adjuvants even for ER-negative breast tumors. -- Highlights: • Glucose uptake by MCF7 and MDA-MB-231 cells is mainly mediated by GLUT1. • QUE and EGCG inhibit cellular glucose uptake thus abolishing the Warburg effect. • This process induces cytotoxicity and proliferation arrest in MCF7 cells. • The flavonoids’ effects are independent of estrogen receptor signalling.

  7. Taxifolin synergizes Andrographolide-induced cell death by attenuation of autophagy and augmentation of caspase dependent and independent cell death in HeLa cells.

    Science.gov (United States)

    Alzaharna, Mazen; Alqouqa, Iyad; Cheung, Hon-Yeung

    2017-01-01

    Andrographolide (Andro) has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi) has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS)-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α) decreased it while the activation of JNK was involved in the cell death of HeLa