bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of anti-HLA antibodies on unrelated cord blood transplantations
Authors: Takanashi Minoko , Atsuta Yoshiko , Fujiwara Koki , Kodo Hideki , Kai Shunro , Sato Hiroyuki , Kohsaki Masatoshi , Azuma Hiroshi , Tanaka Hidenori , Ogawa Atsuko , Nakajima Kazunori , Kato Shunichi 
Published: July 2010

Abstract
The majority of cord blood transplantations (CBTs) have human leukocyte antigen (HLA) disparities. We investigated the impact that patients' pretransplantation anti-HLA antibodies have on the outcome of CBTs. Testing for anti-HLA antibody and its specificity was performed retrospectively at the Japanese Red Cross Tokyo Blood Center with sensitive solid-phase antibody detection assays. Among 386 CBTs, which were first myeloablative stem cell transplantations for malignancies and used a single unit of cord blood, 89 tested positive. Among the antibody-positive group, the cord blood did not have the corresponding HLA type for the antibody in 69 cases (ab-positive), while 20 cases had specificity against the cord blood HLA (positive-vs-CB). Cumulative incidence of neutrophil recovery 60 days after transplantation was 83% (95% confidence interval [CI], 79%-87%) for the antibody-negative group (ab-negative), 73% (95% CI, 61%-82%) for ab-positive, but only 32% (95% CI, 13%-53%) for the positive-vs-CB (P < .0001, Gray test). With multivariate analysis, the ab-positive showed significantly lower neutrophil recovery than the ab-negative (relative risk [RR] = 0.69, 95% CI, 0.49-0.96, p = .027). The positive-vs-CB had significantly lower neutrophil recovery (RR = 0.23, 95% CI, 0.09-0.56, P = .001) and platelet recovery (RR = 0.31, 95% CI, 0.12-0.81, P = .017) than the ab-negative. Patients' pretransplantation anti-HLA antibodies should be tested and considered in the selection of cord blood.
Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation
Authors: Feuchtinger Tobias , Opherk Kathrin , Bethge Wolfgang A. , Topp Max S. , Schuster Friedhelm R. , Weissinger Eva M. , Mohty Mohamad , Or Reuven , Maschan Michael , Schumm Michael , Hamprecht Klaus , Handgretinger Rupert , Lang Peter , Einsele Hermann 
Published: July 2010

Abstract
Cytomegalovirus (CMV) disease and infection refractory to antiviral treatment after allogeneic stem cell transplantation (allo-SCT) is associated with a high mortality. Adoptive transfer of CMV-specific T cells could reconstitute viral im-munity after SCT and could protect from CMV-related complications. However, logistics of producing virus-specific T-cell grafts limited the clinical application. We treated 18 patients after allo-SCT from human leukocyte antigen–mismatched/haploidentical or human leukocyte antigen–matched unrelated donors with polyclonal CMV-specific T cells generated by ex vivo stimulation with pp65, followed by isolation of interferon-γ–producing cells. Patients with CMV disease or viremia refractory to antiviral chemotherapy or both were eligible for adoptive T-cell transfer and received a mean of 21 × 103/kg pp65-specific T cells. In 83% of cases CMV infection was cleared or viral burden was significantly reduced, even in cases of CMV encephalitis (n = 2). Viral control was associated with in vivo expansion of CMV-specific T lymphocytes in 12 of 16 evaluable cases, resulting in reconstitution of antiviral T-cell responses, without graft-versus-host disease induction or acute side effects. Our findings indicate that the infusion of low numbers of CMV-specific T cells is safe, feasible, and effective as a treatment on demand for refractory CMV infection and CMV disease after allo-SCT.
Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia
Authors: Kapitsinou Pinelopi P. , Liu Qingdu , Unger Travis L. , Rha Jennifer , Davidoff Olena , Keith Brian , Epstein Jonathan A. , Moores Sheri L. , Erickson-Miller Connie L. , Haase Volker H. 
Published: July 2010

AbstractThe kidney is the main physiologic source of erythropoietin (EPO) in the adult and responds to decreases in tissue oxygenation with increased EPO production. Although studies in mice with liver-specific or global gene inactivation have shown that hypoxia-inducible factor 2 (Hif-2) plays a major role in the regulation of Epo during infancy and in the adult, respectively, the contribution of renal HIF-2 signaling to systemic EPO homeostasis and the role of extrarenal HIF-2 in erythropoiesis, in the absence of kidney EPO, have not been examined directly. Here, we used Cre-loxP recombination to ablate Hif-2α in the kidney, whereas Hif-2–mediated hypoxia responses in the liver and other Epo-producing tissues remained intact. We found that the hypoxic induction of renal Epo is completely Hif-2 dependent and that, in the absence of renal Hif-2, hepatic Hif-2 takes over as the main regulator of serum Epo levels. Furthermore, we provide evidence that hepatocyte-derived Hif-2 is involved in the regulation of iron metabolism genes, supporting a role for HIF-2 in the coordination of EPO synthesis with iron homeostasis.
Effect of parity on fetal and maternal microchimerism: interaction of grafts within a host?
Authors: Gammill Hilary S. , Guthrie Katherine A. , Aydelotte Tessa M. , Waldorf Kristina M. Adams , Nelson J. Lee 
Published: July 2010

AbstractSmall amounts of genetically foreign cells (microchimerism, Mc) traffic between a mother and fetus during pregnancy. Commonly, these grafts durably persist. For women, multiple naturally acquired Mc grafts can accrue, as they harbor Mc from their own mothers (maternal Mc, MMc) and subsequently acquire fetal Mc (FMc) through pregnancy. The nature of interactions between these naturally acquired grafts may inform, and be informed by, observations in transplantation, including the effect of noninherited maternal HLA antigens (NIMA) and double-unit cord blood transplantation (CBT). We asked whether FMc and MMc are impacted by the addition of new grafts as evaluated by increasing parity. Mc was identified by quantitative PCR for a nonshared polymorphism unique to the Mc source. Despite increasing sources of Mc, FMc did not increase with increasing parity. MMc concentration was significantly lower with increasing parity. The odds ratio for detection of MMc for 2 or more births compared with 1 birth was .11 (95% CI 0.03-0.42, P = .001). These observations suggest that interactions occur among naturally acquired grafts and are of interest in light of recent observations of graft-graft interaction resulting in predominance of 1 unit in double-unit CBT and the correlation of MMc with the NIMA effect.
Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone
Authors: Harousseau Jean-Luc , Palumbo Antonio , Richardson Paul G. , Schlag Rudolf , Dimopoulos Meletios A. , Shpilberg Ofer , Kropff Martin , Kentos Alain , Cavo Michele , Golenkov Anatoly , Komarnicki Mieczyslaw , Mateos Maria-Victoria , Esseltine Dixie-Lee , Cakana Andrew , Liu Kevin , Deraedt William , van de Velde Helgi , San Miguel Jesús F. 
Published: July 2010

AbstractThe phase 3 Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone study in newly diagnosed multiple myeloma patients ineligible for high-dose therapy demonstrated that bortezomib-melphalan-prednisone (VMP) was superior to melphalan-prednisone across all efficacy end points. We assessed the prognostic impact of response on time-to-event parameters in the intent-to-treat population. Patients received nine 6-week cycles of treatment. Time to progression, time to next therapy, and treatment-free interval were associated with quality of response. When European Group for Blood and Marrow Transplantation criteria were used, complete response (CR) was associated with significantly longer time to progression (hazard ratio [HR] = 0.45, P = .004), time to next therapy (HR = 0.46, P = .0004), and treatment-free interval (HR = 0.38, P < .0001) versus partial response, but there was no significant difference in overall survival (HR = 0.87, P = .54); similar differences were seen with CR versus very good partial response by uniform criteria. Quality of response improved with prolonged VMP treatment, with 28% of CRs achieved during cycles 5-9. CR duration appeared similar among patients with “early” (cycles 1-4) and “late” CRs (cycles 5-9) and among patients receiving 9 versus < 9 cycles of bortezomib within VMP. These results highlight that CR is an important treatment goal and support prolonged VMP therapy to achieve maximal response. This study is registered at http://www.clinicaltrials.gov as NCT00111319.
Association between red blood cell transfusions and development of non-Hodgkin lymphoma: a meta-analysis of observational studies
Authors: Castillo Jorge J. , Dalia Samir , Pascual Sheila K. 
Published: July 2010

AbstractThe incidence of non-Hodgkin lymphoma (NHL) has increased steadily for the past few decades. Previous studies have suggested an association between blood transfusions and NHL. The main objective of this study was to evaluate this relationship with a meta-analysis of observational studies. A literature search was undertaken, looking for case-control and cohort studies evaluating the risk of developing NHL in persons who received allogeneic blood transfusions; 14 studies were included. Outcome was calculated and reported as relative risk (RR). Heterogeneity was assessed with Cochrane Q and I2 statistics. Dissemination bias was evaluated by funnel plot visualization and trim-and-fill analysis. Quality assessment was performed with the Newcastle-Ottawa scale. Our analysis showed a RR of developing NHL of 1.05 (95% CI, 0.89-1.25; P = .42) and 1.34 (95% CI, 1.15-1.55; P < .01) in case-control and cohort studies, respectively. When pooling all studies, RR was 1.2 (95% CI, 1.07-1.35; P < .01). In subset analysis, RR of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was 1.66 (95% CI, 1.08-2.56; P = .02). The RR of NHL was elevated in both men and women and in persons receiving transfusions either before or after 1992. Blood transfusions appear to increase the risk of developing NHL; however, the risk of CLL/SLL appears higher than for other NHL subtypes.
The first trimester human placenta is a site for terminal maturation of primitive erythroid cells
Authors: Van Handel Ben , Prashad Sacha L. , Hassanzadeh-Kiabi Nargess , Huang Andy , Magnusson Mattias , Atanassova Boriana , Chen Angela , Hamalainen Eija I. , Mikkola Hanna K. A. 
Published: July 2010

AbstractEmbryonic hematopoiesis starts via the generation of primitive red blood cells (RBCs) that satisfy the embryo's immediate oxygen needs. Although primitive RBCs were thought to retain their nuclei, recent studies have shown that primitive RBCs in mice enucleate in the fetal liver. It has been unknown whether human primitive RBCs enucleate, and what hematopoietic site might support this process. Our data indicate that the terminal maturation and enucleation of human primitive RBCs occurs in first trimester placental villi. Extravascular ζ-globin+ primitive erythroid cells were found in placental villi between 5-7 weeks of development, at which time the frequency of enucleated RBCs was higher in the villous stroma than in circulation. RBC enucleation was further evidenced by the presence of primitive reticulocytes and pyrenocytes (ejected RBC nuclei) in the placenta. Extravascular RBCs were found to associate with placental macrophages, which contained ingested nuclei. Clonogenic macrophage progenitors of fetal origin were present in the chorionic plate of the placenta before the onset of fetoplacental circulation, after which macrophages had migrated to the villi. These findings indicate that placental macrophages may assist the enucleation process of primitive RBCs in placental villi, implying an unexpectedly broad role for the placenta in embryonic hematopoiesis.
In vitro and in vivo targeted delivery of IL-10 interfering RNA by JC virus-like particles
Authors: Chou Meng-Ing , Hsieh Yu-Fan , Wang Meilin , Chang Jinghua Tsai , Chang Deching , Zouali Moncef , Tsay Gregory J 
Published: July 2010

Abstract

Background
RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. Delivering sequences of RNAi in vivo remains a problem. The aim of this study was to use JC virus (JCV) virus-like particles (VLPs) as a vector for delivering RNAi in silencing the cytokine gene of IL-10.

Methods
JCV VLPs were generated by recombinant JCV VP1 protein in yeast expression system. DNA fragment containing IL-10 shRNA was packaged into VLPs by osmotic shock.

Results
In RAW 264.7 cells, IL-10 shRNA was found to reduce IL-10 expression by 85 to 89%, as compared with VLPs alone. IL-10 shRNA did not cross-react with TNF-alpha mRNA or influence the expression of TNF-alpha. In BALB/c mice IL-10 shRNA could reduce 95% of IL-10 secretion. Surprisingly, it also down regulated TNF-alpha expression.

Conclusions
We show for the first time that JCV VLPs empty capsids are competent vectors to deliver RNAi and are nontoxic to cells, suggesting that JCV VLPs is an efficient agent to deliver RNAi in both murine macrophage cells and BALB/c mice. This system provides an efficient means for delivering the RNAi for gene therapy purposes.
Increasing the amylose content of durum wheat through silencing of the SBEIIagenes
Authors: Sestili Francesco , Janni Michela , Doherty Angela , Botticella Ermelinda , D'Ovidio Renato , Masci Stefania , Jones Huw D , Lafiandra Domenico 
Published: July 2010

Abstract

Background
High amylose starch has attracted particular interest because of its correlation with the amount of Resistant Starch (RS) in food. RS plays a role similar to fibre with beneficial effects for human health, providing protection from several diseases such as colon cancer, diabetes, obesity, osteoporosis and cardiovascular diseases. Amylose content can be modified by a targeted manipulation of the starch biosynthetic pathway. In particular, the inactivation of the enzymes involved in amylopectin synthesis can lead to the increase of amylose content. In this work, genes encoding starch branching enzymes of class II (SBEIIa) were silenced using the RNA interference (RNAi) technique in two cultivars of durum wheat, using two different methods of transformation (biolistic and Agrobacterium). Expression of RNAi transcripts was targeted to the seed endosperm using a tissue-specific promoter.

Results
Amylose content was markedly increased in the durum wheat transgenic lines exhibiting SBEIIa gene silencing. Moreover the starch granules in these lines were deformed, possessing an irregular and deflated shape and being smaller than those present in the untransformed controls. Two novel granule bound proteins, identified by SDS-PAGE in SBEIIa RNAi lines, were investigated by mass spectrometry and shown to have strong homologies to the waxy proteins. RVA analysis showed new pasting properties associated with high amylose lines in comparison with untransformed controls. Finally, pleiotropic effects on other starch genes were found by semi-quantitative and Real-Time reverse transcription-polymerase chain reaction (RT-PCR).

Conclusion
We have found that the silencing of SBEIIa genes in durum wheat causes obvious alterations in granule morphology and starch composition, leading to high amylose wheat. Results obtained with two different methods of transformation and in two durum wheat cultivars were comparable.
Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia
Authors: Flamant Lionel , Notte Annick , Ninane Noelle , Raes Martine , Michiels Carine 
Published: July 2010

AbstractBackgroundHypoxia is a hallmark of solid tumors and is associated with metastases, therapeutic resistance and poor patient survival.ResultsIn this study, we showed that hypoxia protected MDA-MB-231 breast cancer cells against paclitaxel- but not epirubicin-induced apoptosis. The possible implication of HIF-1 and AP-1 in the hypoxia-induced anti-apoptotic pathway was investigated by the use of specific siRNA. Specific inhibition of the expression of these two transcription factors was shown to increase apoptosis induced by chemotherapeutic agents under hypoxia indicating an involvement of HIF-1 and AP-1 in the anti-apoptotic effect of hypoxia. After HIF-1 specific inhibition and using TaqMan Human Apoptosis Array, 8 potential HIF-1 target genes were identified which could take part in this protection. Furthermore, Mcl-1 was shown to be a potential AP-1 target gene which could also participate to the hypoxia-induced chemoresistance.ConclusionsAltogether, these data highlight two mechanisms by which hypoxia could mediate its protective role via the activation of two transcription factors and, consecutively, changes in gene expression encoding different anti- and pro-apoptotic proteins.
Echocardiography of isolated subacute left heart tamponade in a patient with cor pulmonale and circumferential pericardial effusion
Authors: Marš Tomaž , Mikolavčič Helena , Salobir Barbara , Podbregar Matej 
Published: July 2010

Abstract
Patients with advanced idiopathic pulmonary artery hypertension have often a chronic pericardial effusion. It is the result of increased transudation and impaired re-absorption due to elevated venous pressure. These patients have pre-existent symptoms and signs of chronic right heart failure. High degree of suspicion is required to detect of development of an atypical form of tamponade with isolated compression of left heart chambers as shown in present case report. Transthoracic echocardiography provides a rapid access to the correct diagnosis, a prompt relief of symptoms following the ultrasound guided pericardiocentesis and important diagnostic tool for regular follow up of patients thereafter as shown in our case report.
IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring
Authors: Matson Adam P , Thrall Roger S , Rafti Ektor , Lingenheld Elizabeth G , Puddington Lynn 
Published: July 2010

AbstractBackgroundThe mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors.ObjectiveThe aim of this study was to investigate the role of offspring neonatal Fc receptor for IgG uptake by intestinal epithelial cells (FcRn) in this breast milk transferred protection from allergy.MethodsAllergic airway disease was induced during pregnancy in C57BL/6 female mice. These allergic mothers foster nursed naive FcRn+/-or FcRn-/-progeny born to FcRn+/-females that were mated to C57BL/6J-FcRn-/-male mice. In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract. Using this model, we were able to investigate how breast milk IgG affected offspring responses to allergic sensitization.ResultsLevels of maternal antibodies absorbed from the breast milk of allergic foster mothers were determined in weanling FcRn-sufficient or -deficient mice. Maternal transmission of allergen-specific IgG1to breastfed FcRn-/-offspring was at levels 103-104lower than observed in FcRn+/-or FcRn+/+mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of allergen-specific IgE and associated pathology.ConclusionsFcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1sufficient to inhibit allergic sensitization in this model.
Concentration of acrylamide in a polyacrylamide gel affects VP4 gene coding assignment of group A equine rotavirus strains with P[12] specificity
Authors: Long-Croal LaShanda M , Wen Xiaobo , Ostlund Eileen N , Hoshino Yasutaka 
Published: July 2010

AbstractBackgroundIt is universally acknowledged that genome segment 4 of group A rotavirus, the major etiologic agent of severe diarrhea in infants and neonatal farm animals, encodes outer capsid neutralization and protective antigen VP4.ResultsTo determine which genome segment of three group A equine rotavirus strains (H-2, FI-14 and FI-23) with P[12] specificity encodes the VP4, we analyzed dsRNAs of strains H-2, FI-14 and FI-23 as well as their reassortants by polyacrylamide gel electrophoresis (PAGE) at varying concentrations of acrylamide. The relative position of the VP4 gene of the three equine P[12] strains varied (either genome segment 3 or 4) depending upon the concentration of acrylamide. The VP4 gene bearing P[3], P[4], P[6], P[7], P[8] or P[18] specificity did not exhibit this phenomenon when the PAGE running conditions were varied.ConclusionsThe concentration of acrylamide in a PAGE gel affected VP4 gene coding assignment of equine rotavirus strains bearing P[12] specificity.
Hereditary combined deficiency of the vitamin K-dependent clotting factors
Authors: Napolitano Mariasanta , Mariani Guglielmo , Lapecorella Mario 
Published: July 2010

Abstract
Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X as well as natural anticoagulants protein C, protein S and protein Z. The spectrum of bleeding symptoms ranges from mild to severe with onset in the neonatal period in severe cases. The bleeding symptoms are often life-threatening, occur both spontaneously and in a surgical setting, and usually involve the skin and mucosae. A range of non-haemostatic symptoms are often present, including developmental and skeletal anomalies. VKCFD is an autosomal recessive disorder caused by mutations in the genes of either gamma-glutamyl carboxylase or vitamin K2,3-epoxide reductase complex. These two proteins are necessary for gamma-carboxylation, a post-synthetic modification that allows coagulation proteins to display their proper function. The developmental and skeletal anomalies seen in VKCFD are the result of defective gamma-carboxylation of a number of non-haemostatic proteins. Diagnostic differentiation from other conditions, both congenital and acquired, is mandatory and genotype analysis is needed to confirm the defect. Vitamin K administration is the mainstay of therapy in VKCFD, with plasma supplementation during surgery or severe bleeding episodes. In addition, prothrombin complex concentrates and combination therapy with recombinant activated FVII and vitamin K supplementation may constitute alternative treatment options. The overall prognosis is good and with the availability of several effective therapeutic options, VKCFD has only a small impact on the quality of life of affected patients.