bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of storing whole blood at 22°C for up to 24 hours with and without rapid cooling on the quality of red cell concentrates and fresh‐frozen plasma
Authors: Wilsher Claire , Garwood Margaret , Sutherland Janet , Turner Craig , Cardigan Rebecca 
Published: July 2008

BACKGROUND: Storage of whole blood (WB) for less than 24 hours at ambient temperature is permitted in Europe, but data directly comparing storage with and without active cooling are lacking, which was investigated and compared to current standard methods.STUDY DESIGN AND METHODS: WB was stored in one of four different ways for 24 hours after donation before processing on Day 1 to red cell concentrates (RCCs) in saline‐adenine‐glucose‐mannitol and fresh‐frozen plasma (FFP; n = 20 each): 1) at 22°C in plastic trays, 2) in cooling devices (Compocool II, NPBI), 3) at 4°C, or 4) processed from WB without storage less than 8 hours from donation (Day 0).RESULTS: 2,3‐Diphosphoglycerate (2,3‐DPG) in RCCs were lower after ambient storage compared with those processed on Day 0 or after 4°C storage. Rapid cooling slowed the loss of 2,3‐DPG but levels were undetectable by Day 21 with any method. On Day 42 of RCC storage, there was no significant difference between storage methods in levels of adenosine triphosphate or hemolysis. Potassium levels were lower in RCCs from WB stored at ambient compared with those produced on Day 0, regardless of the use of cooling plates. FFP produced from WB on Day 0 or after storage at ambient with or without active cooling met UK specifications (>75% of units >0.70 IU/mL Factor VIII).CONCLUSION: These data suggest that RCCs and FFP produced from WB that has been stored at ambient temperature with or without active cooling are of acceptable quality compared with those produced using current standard methods in the United Kingdom.
Investigation of the effect of kaolin and tissue factor–activated citrated whole blood, on clot forming variables, as evaluated by thromboelastography
Authors: Johansson Pär I. , Bochsen Louise , Andersen Søren , Viuff Dorthe 
Published: July 2008

BACKGROUND: The Thrombelastograph (TEG; Haemoscope Corp.) analyzes clot formation in whole blood (WB) and treatment based on this analysis has been shown to reduce transfusion requirements in liver and cardiac surgery when compared to conventional coagulation analysis. Implementing TEG as a routine laboratory‐based analysis, however, requires validation of the activators employed and the effect of storage of the WB sample in citrate before analysis.STUDY DESIGN AND METHODS: The effect of kaolin, tissue factor (TF) 1:17,000, or TF 1:42,500 on TEG clotting time (R), Angle (velocity of clot formation), and maximum clot strength (amplitude [MA]) were evaluated, together with day‐to‐day variation, the coefficient of variance (CV%), and the effect of citrate storage time.RESULTS: Clot formation variables were equally affected by TF 1:17,000 and kaolin activation, whereas R was significantly longer when TF 1:42,500 was used. The CV for the different variables varied from 3 to 13 percent with no significant differences between assays. Storage of citrated WB significantly affected the TEG variables in a hypercoagulable direction. Only the R, however, was significantly affected (12%) when samples rested for 0 and 30 minutes were evaluated with kaolin as the activator.CONCLUSION: The TEG assays evaluated were reproducible and present with an acceptable CV% for routine clinical practice. Kaolin and TF 1:17,000 equally affected the clot formation variables. Storage of WB for up to 30 minutes in citrate did not, except for R, affect clot formation variables when kaolin was used as activator allowing for immediate analysis when the sample arrives in the laboratory.
Serological studies of piperacillin antibodies
Authors: Leger Regina M. , Arndt Patricia A. , Garratty George 
Published: July 2008

BACKGROUND: Penicillin‐induced immune hemolytic anemia (IHA) is associated with immunoglobulin G antipenicillin detected by testing penicillin‐coated red blood cells (RBCs). Antibodies to piperacillin, a semisynthetic penicillin, would be expected to react similarly; however, antipiperacillin can be detected by testing in the presence of the drug. Piperacillin is commonly used in combination with tazobactam, which causes nonimmunologic protein adsorption onto RBCs. In six cases of piperacillin‐induced IHA, reactivity with piperacillin‐coated RBCs was not similar to reactivity of antipenicillin with penicillin‐coated RBCs.STUDY DESIGN AND METHODS: Antipiperacillin was tested against piperacillin‐coated RBCs prepared using different pH buffers. Plasma from blood donors and sera/plasma from patients were tested with piperacillin‐coated, penicillin‐coated, and uncoated RBCs. Hapten inhibition studies were performed using different concentrations of piperacillin. Donors' plasma were tested in the presence of piperacillin; sera from patients with IHA were tested in the presence of tazobactam.RESULTS: Piperacillin required high pH for binding to RBCs. Agglutination of piperacillin‐coated RBCs was observed in 91 percent of donors' and 49 percent of patients' plasma and was inhibited by piperacillin. In contrast to patients with IHA due to piperacillin, donors' plasma tested in the presence of piperacillin did not react. Tazobactam antibodies were not detected.CONCLUSION: A high percentage of donors' and patients' plasma contain an antibody to piperacillin or a chemically related structure detected by testing with piperacillin‐coated RBCs. A diagnosis of piperacillin‐induced IHA should not be made solely on the reactivity of a patient's plasma/serum with piperacillin‐ or piperacillin/tazobactam‐coated RBCs; testing in the presence of piperacillin is more reliable.
The critical role of plasmapheresis in ABO‐incompatible renal transplantation
Authors: Tobian Aaron A.R. , Shirey R. Sue , Montgomery Robert A. , Ness Paul M. , King Karen E. 
Published: July 2008

BACKGROUND: Thousands of patients with chronic renal failure die yearly and are unable to have a kidney transplant due to the severe shortage of donors. Therapeutic plasma exchange (TPE) is performed to remove ABO antibodies and permit ABO‐incompatible (ABO‐I) kidney transplants, but there is only limited research within this area and a lack of standardized protocols for TPE. This article reviews the literature to provide a historical perspective of TPE for ABO‐I kidney transplantation and also provides the Johns Hopkins Hospital protocol with a focus on both titers and TPE.STUDY DESIGN AND METHODS: The TPE treatment plan is based on ABO titers with the goal of a titer of 16 or less at the anti‐human globulin (AHG) phase before surgery. Pretransplant therapy consists of every‐other‐day TPE followed immediately by cytomegalovirus hyperimmune globulin. ABO antibody titers are closely monitored before and after transplantation. After transplantation, TPE therapy is performed for all patients to prevent rebound of anti‐A and anti‐B titers until tolerance or accommodation occurs. TPE is discontinued and reinstituted based on the clinical criteria of creatinine levels, biopsy results, and ABO titer.RESULTS: Fifty‐three ABO‐I kidney transplants have been completed with no episodes of hyperacute antibody‐mediated rejection (AMR) and only three episodes of AMR. One‐year death‐censored graft survival is 100 percent and patient survival is 97.6 percent.CONCLUSIONS: While randomized clinical trials are needed to evaluate the optimal method and protocol to remove ABO antibodies, the current literature and our results indicate a critical role for TPE in ABO‐I renal transplantation.
Interleukin 8 is differently expressed and modulated by PAR‐1 activation in early and late endothelial progenitor cells
Authors: Smadja David M. , Bièche Ivan , Susen Sophie , Mauge Laetitia , Laurendeau Ingrid , d’Audigier Clément , Grelac Françoise , Emmerich Joseph , Aiach Martine , Gaussem Pascale 
Published: July 2008

AbstractThe proinflammatory chemokine interleukin 8 exerts potent angiogenic effects on endothelial cells by interacting with its receptors CXCR1 and CXCR2. As thrombin is also a potent inflammatory factor, and as endothelial progenitor cells (EPC) express functional PAR‐1 thrombin receptor, we examined whether PAR‐1 stimulation interferes with the IL‐8 pathway in EPC. EPC were obtained from adult blood (AB) and cord blood (CB). The effect of PAR‐1 stimulation by the peptide SFLLRN on IL‐8, CXCR1 and CXCR2 expression was examined by RTQ‐PCR and at the protein level in AB and CB late EPC and in AB early EPC. Specific siRNA was used to knock down PAR‐1 expression. TheIL‐8gene was expressed strongly in AB early EPC and moderately in late EPC. In contrast, CXCR1 and CXCR2 gene expression was restricted to AB early EPC. The IL‐8 level in AB early EPC conditioned medium was high in basal conditions and did not change after PAR‐1 activation. By contrast, IL‐8 secretion by late EPC was low in basal conditions and strongly up‐regulated upon PAR‐1 activation. PAR‐1 activation induced a number of genes involved in activating protein‐1 (AP‐1) and nuclear factor (NF)‐κB pathways. Conditioned medium of PAR‐1‐activated late EPC enhanced the migratory potential of early EPC, and this effect was abrogated by blocking IL‐8. Target‐specific siRNA‐induced PAR‐1 knockdown, and fully inhibited PAR‐1‐induced IL‐8 synthesis. In conclusion, PAR‐1 activation induces IL‐8 synthesis by late EPC. This could potentially enhance cooperation between late and early EPC during neovascularization, through a paracrine effect.
CFTR expression from a BAC carrying the complete human gene and associated regulatory elements
Authors: Kotzamanis George , Abdulrazzak Hassan , Gifford‐Garner Jennifer , Haussecker Pei Ling , Cheung Wing , Grillot‐Courvalin Catherine , Harris Ann , Kittas Christos , Kotsinas Athanasios , Gorgoulis Vassilis G. , Huxley Clare 
Published: July 2008

AbstractThe use of genomic DNA rather than cDNA or mini‐gene constructs in gene therapy might be advantageous as these contain intronic and long‐range control elements vital for accurate expression. For gene therapy of cystic fibrosis though, no bacterial artificial chromosome (BAC), containing the whole CFTR gene is available. We have used Red homologous recombination to add a to a previously described vector to construct a new BAC vector with a 250.3‐kb insert containing the whole coding region of the CFTR gene along with 40.1 kb of DNA 5′ to the gene and 25 kb 3′ to the gene. This includes all the known control elements of the gene. We evaluated expression by RT‐PCR in CMT‐93 cells and showed that the gene is expressed both from integrated copies of the BAC and also from episomes carrying the oriP/EBNA‐1 element. Sequencing of the human CFTR mRNA from one clone showed that the BAC is functional and can generate correctly spliced mRNA in the mouse background. The BAC described here is the only CFTR genomic construct available on a convenient vector that can be readily used for gene expression studies or in vivo studies to test its potential application in gene therapy for cystic fibrosis.
A leaky blood–brain barrier, fibrinogen infiltration and microglial reactivity in inflamed Alzheimer’s disease brain
Authors: Ryu Jae K. , McLarnon James G. 
Published: July 2008

AbstractThis study has used immunohistochemical examination of tissue obtained from Alzheimer’s disease (AD) brains and rat hippocampus injected with Aβ1‐42 peptide to determine effects of induced inflammatory reactivity on integrity of blood–brain barrier (BBB) and viability of neurons. Tissue from AD, but not non‐demented, brains exhibited a diffuse pattern of staining for fibrinogen and immunoglobulin (IgG) indicative of BBB leakiness with considerable fibrinogen immunoreactivity (ir) appearing in association with Aβ deposits. Immunostaining for the endothelial cell specific glycoprotein, von Willebrand factor, showed morphological evidence for altered blood vessels in AD tissue. AD brains also demonstrated extensive areas of fibrinogen ir in association with microglial reactivity. In vivo, intra‐hippocampal injection of Aβ1‐42 caused time‐dependent (1–7 days after injection) increases in double staining of fibrinogen with areas of microgliosis. Two independent pharmacological strategies were employed to examine how Aβ1‐42 stimulation (7 days injection) may be linked to neurodegeneration. The defibrinogenating compound, ancrod, reduced inflammatory reactivity, levels of parenchymal fibrinogen and IgG, and was neuroprotective. These results prompted use of Aβ1‐42 plus fibrinogen as a novel in vivo inflammatory stimulus and this combination significantly enhanced inflammatory reactivity, vascular perturbations and neuronal damage compared to Aβ1‐42 alone. A second approach, using anti‐Mac‐1 (antibody for antigen CD11b) to block activation of microglia, was highly effective in attenuating effects of Aβ1‐42 plus fibrinogen amplification of inflammatory and vascular responses and conferred significant neuroprotection. The overall findings from study of AD tissue and in vivo in Aβ1‐42 and Aβ1‐42 plus fibrinogen stimulated rat hippocampus suggest microglial responses to promote increased extravasation of blood protein as a critical component in amplifying inflammatory reactivity and causing neuronal damage in inflamed AD brain.
Chemotherapy drug response in ovarian cancer cells strictly depends on a cathepsin D‐Bax activation loop
Authors: Castino Roberta , Peracchio Claudia , Salini Alessandra , Nicotra Giuseppina , Trincheri Nicol F. , Démoz Marina , Valente Guido , Isidoro Ciro 
Published: July 2008

AbstractThe ovarian cancer cell lines A2780 (wild‐type p53) and NIHOVCAR3 (mutated p53) showed, respectively, sensitivity and resistance towards several chemotherapy drugs. We hypothesized that the two cell lines differ in their ability to activate the intrinsic death pathway and have, therefore, dissected the lysosome‐mitochondrion signalling pathway by pharmacological inhibition or genetic manipulation of key regulators and executioners. Biochemical and morphological confocal fluorescence studies showed that: (1) In A2780 cells bcl‐2 is expressed at an undetectable level, whereas Bax is expressed at a rather high level; by contrast, bcl‐2 is highly expressed and Bax is expressed at extremely low levels in NIHOVCAR3 cells; (2) Chemotherapy treatment reduced the expression of bcl‐2 in NIHOVCAR3 cells, yet these cells resisted to drug toxicity; (3) Cathepsin D (CD), not cathepsin B or L, mediates the activation of the mitochondrial intrinsic death pathway in A2780 cells; (4) Lysosome leakage and cytosolic relocation of CD occurs in the chemosensitive A2780 cells, not in the chemoresistant NIHOVCAR3 cells; (5) Bax is essential for the permeabilization of both lysosomes and mitochondria in A2780 cells exposed to chemotherapy drugs; (6) CD activity is mandatory for the oligomerization of Bax on both mitochondrial and lysosomal membranes; (7) Bax activation did not occur in the resistant NIHOVCAR3 cells despite their high content in CD. The present data are consistent with a model in which on treatment with a cytotoxic drug the activation of a CD‐Bax loop leads to the generalized permeabilization of lysosomes and eventually of mitochondria, thus reaching the point of no return, and culminates with the activation of the caspase cascade. Our data also imply that dysfunctional permeabilization of lysosomes contributes to the development of chemoresistance.
The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo
Authors: Jones Jon , Juengel Eva , Mickuckyte Ausra , Hudak Lukasz , Wedel Steffen , Jonas Dietger , Blaheta Roman A. 
Published: July 2008

AbstractHistone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre‐clinical renal cell carcinoma (RCC) models. Caki‐1, KTC‐26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti‐tumoural potential of VPA combined with low‐dosed interferon‐α (IFN‐α) was also investigated. VPA significantly and dose‐dependently up‐regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki‐1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA‐treated animals. VPA–IFN‐α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti‐tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC.
Importins and exportins in cellular differentiation
Authors: Okada Norihisa , Ishigami Yoko , Suzuki Takuji , Kaneko Akihiro , Yasui Kensuke , Fukutomi Ryuuta , Isemura Mamoru 
Published: July 2008

Introduction
Importins and exportins
NLS and NES
Cargo molecules
Importins and exportins In cellular differentiation
Concluding remarks
AbstractThe importin/exportin transport system provides the machinery involved in nucleocytoplasmic transport. Alterations of the levels of importins and exportins may play crucial roles in development, differentiation and transformation. Employing human leukaemia HL‐60 cells, we and others have revealed the differentiation‐associated changes in the protein and gene expression of these factors. The recent finding that a switch to the importin‐α subtype triggers neural differentiation of embryonic stem cells underscores the importance of nucleocytoplasmic transport factors in cellular events. This review focuses on current research into the roles of importins and exportins in cell differentiation.
Optical Three‐Dimensional Scanning Acquisition of the Position of Osseointegrated Implants: An in vitro Study to Determine Method Accuracy and Operational Feasibility
Authors: Del Corso Marco , Abà Giancarlo , Vazquez Lydia , Dargaud Jacques , Ehrenfest David M. Dohan 
Published: July 2008

ABSTRACTPurpose: Manufacturing complex prosthetic framework on osseointegrated implants requires precision at every step of execution. The purpose of this study was to verify the possibility of applying the technology of image acquisition to determine the spatial position of osseointegrated implants.Materials and Methods: An optical three‐dimensional scanning technique was employed: its measurement systematic error (bias) was calculated by comparing the results with the detection on a coordinates measuring machine. Measurements were carried out on master casts by doing an in vitro simulation of intraoral conditions.Result: This study showed that the bias error value of the three‐dimensional optical acquiring system was situated between 14 and 21 µm.Conclusion: As far as the accuracy is concerned, it seems possible to use the three‐dimensional image acquisition technology as a valid alternative to traditional impression‐making procedures. However, the bias levels obtained in this in vitro study will have to be confirmed in a clinical trial.
Attitudes of Homeless and Drug‐Using Youth Regarding Barriers and Facilitators in Delivery of Quality and Culturally Sensitive Health Care
Authors: Christiani Ashley , Hudson Angela L. , Nyamathi Adeline , Mutere Malaika , Sweat Jeffrey 
Published: July 2008

PROBLEM:  Major barriers to care included a lack of culturally competent, accessible care despite the proximity of numerous health service agencies serving homeless youth. METHODS:  A qualitative approach using semistructured focus groups was used to assess the perspectives of 54 homeless and drug‐using youth, aged 18–24 years, recruited from street‐ and shelter‐based settings. FINDINGS:  Substance use was perceived as an adaptive response to psychological pain and survival on the streets as well as a health risk and barrier to care. CONCLUSIONS:  Facilitators to care and suggestions for improved health delivery and quality of care included utilization of health “mentors” to assist in navigating the medical system, cultural competency enhancements, improved amenities in clinic wait areas, and expanded pharmaceutical services.
Autumn sowing increases severity of pasmo (Mycosphaerella linicola) on linseed in the UK
Authors: Perryman S.A.M , Gladders P. , Fitt B.D.L. 
Published: July 2008

AbstractSurveys and field experiments showed pasmo to be the most serious disease affecting UK winter linseed in the 1997–98, 1998–99 and 1999–2000 growing seasons. Survey data indicated that pasmo was widespread in England and Scotland, causing extensive loss of leaves and stem and capsule symptoms, on both winter and spring linseed crops. In winter linseed experiments at ADAS Boxworth and Rothamsted, when severe epidemics occurred (1997–98 and 1999–2000), control of pasmo with one or two MBC fungicide sprays increased yield. In experiments when severe pasmo epidemics did not occur (1998–99), fungicide applications did not increase yield. In all three growing seasons, large numbers of air‐borne Mycosphaerella linicola ascospores were collected in the summer months. At the time when the winter linseed crop was emerging and becoming established in October/November, there were more air‐borne M. linicola ascospores in 1999 than in 1998. April/May rainfall was much greater in 1998 (135 mm) and 2000 (223 mm), when severe pasmo epidemics developed by July, than in 1999 (68 mm) when disease severity in July was less. Regression analyses suggested that yield decreased as percentage area affected by pasmo on leaves or stems in July increased. The formulae relating yield loss to pasmo severity, derived from these experiments, were combined with disease survey data to estimate, retrospectively, the UK national losses from pasmo. Estimated national losses from pasmo on winter linseed, although >50% of crops were sprayed with fungicide, were approximately £2.9M in 1998, £1.6M in 1999 and £0.37M in 2000 (when the area of winter linseed had decreased greatly). Estimated combined losses on winter and spring linseed were approximately £14.8M in 1998, £34.9M in 1999 and £11.0M in 2000.