bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–B-Cell Monoclonal Antibody Treatment of Severe Posttransplant B-Lymphoproliferative Disorder: Prognostic Factors and Long-Term Outcome
Authors: Benkerrou Malika , Jais Jean-Philippe , Leblond Véronique , Durandy Anne , Sutton Laurent , Bordigoni Pierre , Garnier Jane Luce , Le Bidois Jérôme , Le Deist Françoise , Blanche Stéphane , Fischer Alain 
Published: October 2019

B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus–transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T-cell infusions has given promising results in BMT recipients. We previously reported that administration of two monoclonal anti–B-cell antibodies (anti-CD21 and anti-CD24) could contribute to the control of oligoclonal BLPD. Here we report the long-term results of treatment with these monoclonal anti–B-cell antibodies for cases of severe BLPD. In an open multicenter trial, 58 patients in whom aggressive B-cell lymphoproliferative disorder developed after BMT (n = 27) or organ (n = 31) transplantation received 0.2 mg/kg/d of specific anti-CD21 and anti-CD24 murine monoclonal antibodies (MoAbs) for 10 days. The treatment was well tolerated. Thirty-six of the 59 episodes of BLPD in the 58 patients presented complete remission (61%). The relapse rate was low (3 of 36, 8%). Multivariate analysis identified the following risk factors for partial or no response to anti–B-cell MoAb therapy: multivisceral disease (P ≤ .005), central nervous system involvement (P ≤ .05), and late onset of BLPD (P ≤ .005). The overall long-term survival was 46% (median follow-up, 61 months); it was lower among BMT patients (35%) than organ transplant patients (55%). None of the patients who had received BMT for hematological malignancy survived for 1 year. Eight of these 11 patients presented monoclonal BLPD. Tumor burden was the only other variable that contributed significantly to poor survival. Thus, as assessed from this long-term study, the use of anti–B-cell MoAbs therefore appears to be a safe and relatively effective therapy for severe posttransplant BLPD.© 1998 by The American Society of Hematology.
Gene Transfer in Dendritic Cells, Induced by Oral DNA Vaccination With Salmonellatyphimurium, Results in Protective Immunity Against a Murine Fibrosarcoma
Authors: Paglia Paola , Medina Eva , Arioli Ivano , Guzman Carlos A. , Colombo Mario P. 
Published: October 2019

A live attenuated AroA− auxotrophic mutant ofSalmonella typhimurium (SL7207) has been used as carrier for the pCMVβ vector that contains the β-galactosidase (β-gal) gene under the control of the immediate early promoter ofCytomegalovirus (CMV). We tested whether orally administered bacterial carrier could enter and deliver the transgene to antigen-presenting cells (APCs) through the natural enteric route of infection and whether β-gal expression could generate a protective response against an aggressive murine fibrosarcoma transduced with the β-gal gene (F1.A11) that behaves operationally as a tumor-associated antigen. After three courses, at 15-day intervals, mice developed both cell-mediated and systemic humoral responses to β-gal. Mice vaccinated with the Salmonella harboring pCMVβ, but not with plasmid-less carrier, showed resistance to a challenge with F1.A11 cells. These experiments suggest that Salmonella-based DNA immunization allows us to specifically target antigen expression in vivo to APCs. To prove that the transgene is actually expressed by APCs as a function of an eukaryotic promoter, the green fluorescent protein (GFP) was placed under the control of either the eukariotic CMV or a prokaryotic promoter. Using cytofluorometric analysis, GFP was detected only in splenocytes of mice receiving a Salmonella carrier harboring GFP under the CMV promoter. These results indicate that transgene expression occurs because of a Salmonella-mediated gene transfer to eukaryotic cells. Finally, approximately 19% of the splenocytes expressed GFP. Among them, F4/80+ macrophages and CD11cbright dendritic cells (DCs) were scored as positive for GFP expression. Extensive work has been performed trying to optimize the way to transfect DCs, ex vivo, with genes coding for relevant antigens. We show here, for the first time, that DCs can be directly and specifically transduced in vivo such to induce DNA vaccination against tumors.© 1998 by The American Society of Hematology.
Adhesive and Signaling Properties of a Naturally Occurring Allele of Glycoprotein IIIa With an Amino Acid Substitution Within the Ligand Binding Domain—The Pena/PenbPlatelet Alloantigenic Epitopes
Authors: Wang Ronggang , Newman Peter J. 
Published: October 2019

Platelet membrane glycoprotein IIIa (GPIIIa) is the most polymorphic integrin subunit in man, with at least seven recognized allelic isoforms present in the human gene pool. Whether these allelic variants of the GPIIb-IIIa complex differ in the ability to interact with the adhesive ligand fibrinogen (Fg) is still unknown. Since the Pena and Penb allelic forms of GPIIIa are distinguished by a single Arg143Gln amino acid substitution within the RGD binding domain of GPIIIa and anti-Pena human alloantibodies have been shown to bind GPIIb-IIIa on the platelet surface and inhibit ADP-induced platelet aggregation, we expressed both forms of this integrin in Chinese hamster ovary (CHO) cells and examined the relative adhesive properties. Both allelic forms of GPIIb-IIIa were expressed on the cell surface and were recognized by a well-characterized panel of murine and human monoclonal and polyclonal antibodies. Like Pena, the Penb form of GPIIb-IIIa could undergo conformational changes in response to RGD peptide binding, and could be induced by activating antibodies to bind Fg and the Fg mimetic antibody P1-55. The binding affinity for Fg of the Pena form of the GPIIb-IIIa complex was not significantly different from that of the Penb form, nor was its ability to signal to focal adhesion kinase, suggesting that Arg143Gln polymorphism has little or no effect on integrin function. Examination of the functional consequences of other integrin polymorphisms may be necessary to determine whether they constitute a risk factor for thrombosis or hemorrhage.© 1998 by The American Society of Hematology.
The Presence of Typical and Atypical BCR-ABL Fusion Genes in Leukocytes of Normal Individuals: Biologic Significance and Implications for the Assessment of Minimal Residual Disease
Authors: Bose Shikha , Deininger Michael , Gora-Tybor Joanna , Goldman John M. , Melo Junia V. 
Published: October 2019

The number of genetic lesions necessary to generate leukemia in humans is unknown, but it is possible that certain specific abnormalities, eg, fusion genes, known to be associated with acute and chronic leukemia are produced relatively frequently in human cells but require other events to occur before the leukemia becomes manifest. We investigated this possibility by studying peripheral blood leukocytes from normal individuals and various hematopoietic cell lines for the presence and expression of the p210 and the p190 types of the BCR-ABL gene associated with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia. We used two-step reverse transcriptase-polymerase chain reaction (RT-PCR) assays in which batches of 108 cells per sample were tested in 40 replicate reactions. We estimate that this assay is 1.5 logs more sensitive than the two-step RT-PCR assays that we use routinely to assess minimal residual disease. BCR-ABL fusion gene transcripts of various configurations were found in circulating leukocytes from 12 of the 16 healthy adults analyzed. Transcripts with an e1a2 junction (p190 BCR-ABL) were present in 11 and p210-type transcripts with b2a2 and/or b3a2 junctions were detected in 4 individuals. The same RT-PCR assays in non-CML cell lines showed the presence of classical or aberrant p210-type mRNA in 3 of 7 lines and of p190-type transcripts in all 7 lines of hematopoietic origin (HL60, KG1, U937, Kasumi, Jurkat, JVM13, and JVM25), whereas the NIH3T3 murine fibroblast line was reproducibly negative for these fusion genes. These findings confirm and extend previous reports on the detection of leukemia-associated genes in normal leukocytes and suggest that certain fusion genes are generated relatively frequently in hematopoietic cells, but only infrequently do the cells acquire the additional changes necessary to produce leukemia in humans. Although there is only a small probability that such innocent BCR-ABL–carrying leukocytes are detected by conventional RT-PCR assays, they may be the source of some sporadically positive tests in leukemia patients in long-term remission.
© 1998 by The American Society of Hematology.
High-resolution Transmission Electron Microscopy Characterization of the Structure of Cu Precipitate in a Thermal-aged Multicomponent Steel
Authors: Han Lizhan , Liu Qingdong , Gu Jianfeng 
Published: October 2019

Abstract
High-dispersed nanoscale Cu precipitates often contribute to extremely high strength due to precipitation hardening, and whereas usually lead to degraded toughness for especially ferritic steels. Hence, it is important to understand the formation behaviors of the Cu precipitates. High-resolution transmission electron microscopy (TEM) is utilized to investigate the structure of Cu precipitates thermally formed in a high-strength low-alloy (HSLA) steel. The Cu precipitates were generally formed from solid solution and at the crystallographic defects such as martensite lath boundaries and dislocations. The Cu precipitates in the same aging condition have various structure of BCC, 9R and FCC, and the structural evolution does not greatly correlate with the actual sizes. The presence of different structures in an individual Cu precipitate is observed, which reflects the structural transformation occurring locally to relax the strain energy. The multiply additions in the steel possibly make the Cu precipitation more complex compared to the binary or the ternary Fe–Cu alloys with Ni or Mn additions. This research gives constructive suggestions on alloying design of Cu-bearing alloy steels.
Assessment of mercury pollution sources in beach sand and coastal soil by speciation analysis
Authors: Gallego José Luis R. , López-Antón Maria Antonia , de la Rosa Deva Martínez , Rodríguez-Valdés Eduardo , García-González Nerea , Rodríguez Elena , Martínez-Tarazona Maria Rosa 
Published: October 2019

Abstract

Background
An essential requisite for controlling and monitoring mercury in the environment is to identify its species in different types of soils and sediments, as this will help not only to establish its mobility in the environment and ecosystem and the degree of its toxicity, but also to establish the source of contamination. The objective of this work was to identify the origin of mercury in beach sands and soil taken from a coastal region with previously high mining and industrial activity by characterizing the mercury species using the technique known as thermal desorption (HgTPD).

Results
Apart from quartz, the main mineral species identified in the raw sands and soil were calcite, fluorite and barite. The concentration of mercury ranges from 5 to 23 µg g−1, and although it is distributed in different proportions in the function of the size, thermal desorption profiles demonstrated that the mercury species present in the samples do not vary with the mercury concentration and the particle size. By means of HgTPD, mercury oxide (HgO) was identified in the beach sands, whereas mercury sulfide (HgS) was found in the soil sample taken from the vicinity of the beach. Complementary methodologies foster the HgTPD conclusions and verify that mercury is present mostly in insoluble stable (HgS) or low-mobility (HgO) forms in the samples studied. Analyses by ICP-MS after sequential extraction and HPLC separation of mercury species show that inorganic mercury is the predominant form in the samples.

Conclusions
The technique HgTPD is a very useful tool to ascertain the origin of mercury in contaminated beach sands and shoreline soils. In the particular area studied in this work, the species identified indicate that previous mining activity was the source of the mercury and rule out the possibility that contamination is derived from coal combustion activities ongoing in the region.
Quantifying mechanisms in neurodegenerative diseases (NDDs) using candidate mechanism perturbation amplitude (CMPA) algorithm
Authors: Karki Reagon , Kodamullil Alpha Tom , Hoyt Charles Tapley , Hofmann-Apitius Martin 
Published: October 2019

Abstract

Background
Literature derived knowledge assemblies have been used as an effective way of representing biological phenomenon and understanding disease etiology in systems biology. These include canonical pathway databases such as KEGG, Reactome and WikiPathways and disease specific network inventories such as causal biological networks database, PD map and NeuroMMSig. The represented knowledge in these resources delineates qualitative information focusing mainly on the causal relationships between biological entities. Genes, the major constituents of knowledge representations, tend to express differentially in different conditions such as cell types, brain regions and disease stages. A classical approach of interpreting a knowledge assembly is to explore gene expression patterns of the individual genes. However, an approach that enables quantification of the overall impact of differentially expressed genes in the corresponding network is still lacking.

Results
Using the concept of heat diffusion, we have devised an algorithm that is able to calculate the magnitude of regulation of a biological network using expression datasets. We have demonstrated that molecular mechanisms specific to Alzheimer (AD) and Parkinson Disease (PD) regulate with different intensities across spatial and temporal resolutions. Our approach depicts that the mitochondrial dysfunction in PD is severe in cortex and advanced stages of PD patients. Similarly, we have shown that the intensity of aggregation of neurofibrillary tangles (NFTs) in AD increases as the disease progresses. This finding is in concordance with previous studies that explain the burden of NFTs in stages of AD.

Conclusions
This study is one of the first attempts that enable quantification of mechanisms represented as biological networks. We have been able to quantify the magnitude of regulation of a biological network and illustrate that the magnitudes are different across spatial and temporal resolution.
Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey
Authors: Wang Hao , Zhu Xiaoqi , Shen Junyan , Zhao En-Feng , He Dajun , Shen Haitao , Liu Hailiang , Zhou Yongxin 
Published: October 2019

Abstract

Background
The underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein.

Results
Between the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice.

Conclusions
This first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.
Enhanced IFN-γ, but not IL-2, response to Mycobacterium tuberculosis antigens in HIV/latent TB co-infected patients on long-term HAART
Authors: Desalegn Girmay , Tsegaye Aster , Gebreegziabiher Dawit , Aseffa Abraham , Howe Rawleigh 
Published: October 2019

AbstractBackgroundHIV-infected individuals with latent TB infection are at increased risk of developing active TB. HAART greatly reduces the incidence rate of TB in HIV-infected patients and reconstitutesMycobacterium tuberculosis (M. tuberculosis)-specific immune response in the first 12 months of therapy. The durability of the anti-mycobacterial immune restoration after a year of HAART however remains less investigated.MethodA cross-sectional study was conducted to evaluateM. tuberculosis-specific functional immune responses in HIV/latent TB co-infected patients who were on HAART for at least 1.5 up to 9 years as compared to HAART-naïve patients. Three-hundred sixteen HIV-infected patients without active TB were screened by tuberculin skin testing forM. tuberculosisinfection and peripheral blood mononuclear cells (PBMCs) were isolated from 61 HIV/latent TB co-infected patients (30 HAART-naïve and 31 HAART-treated). IFN-γ and IL-2 ELISPOT as well as CFSE cell proliferation assays were performed after stimulation withM. tuberculosisantigens PPD and ESAT-6.ResultThe median frequency of PPD and ESAT-6 specific IFN-γ secreting cells was significantly higher in the HAART-treated patients as compared to HAART-naïve patients,p = 0.0021 andp = 0.0081 respectively. However, there was no significant difference in the median frequency of IL-2 secreting cells responding to PPD (p = 0.5981) and ESAT-6 (p = 0.3943) antigens between HAART-naïve and-treated groups. Both IFN-γ and IL-2 responses were independent of CD4+T cell count regardless of the HAART status. Notably, the frequency of PPD and ESAT-6 specific IL-2 secreting cells was positively associated with CD4+T cell proliferation while inversely correlated with duration of HAART, raising the possibility thatM. tuberculosis-specific IL-2 response that promote the antigen-specific CD4+T cell proliferation diminish with time on antiretroviral therapy in HIV/latent TB co-infected patients.ConclusionThis study shows an increasedM. tuberculosis-specific IFN-γ, but not IL-2, response in HIV/latent TB co-infected patients with long-term HAART, consistent with only partial immune restoration. Future studies should, therefore, be done to prospectively define the rate and extent to which functional immune responses toM. tuberculosisare restored after long-term HAART.
Uncompleted emergency department care and discharge against medical advice in patients with neurological complaints: a chart review
Authors: Hoyer Carolin , Stein Patrick , Alonso Angelika , Platten Michael , Szabo Kristina 
Published: October 2019

AbstractBackgroundUncompleted emergency department care and against-medical-advice discharge represent relevant medical problems with impact on patient safety and potential medicolegal and socioeconomic consequences. They may also indicate structural or procedural problems in the emergency department (ED) relating to patient management and flow. While patients with neurological complaints frequently leave the ED against medical advice or without being seen, no dedicated analysis of this group of patients aiming at the identification of characteristics associated with irregular ED discharge has been performed so far.MethodsA chart review was performed of all patients with neurological complaints presenting to a German interdisciplinary emergency department between January and December 2017 for neurological evaluation. Demographics, mode of presentation, process times, presenting symptoms and diagnosis were recorded. Patients leaving against medical advice after an informed consent discussion and signing of documentation (DAMA) or leaving prematurely without notifying ED staff (PL) were compared to the total of patients who were admitted or discharged (non-DAMA/PL).ResultsOf all patients presenting with neurological symptoms or complaints, 3% left against medical advice and 2.2% left prematurely. DAMA/PL patients were younger (p < .001), and they were more frequently self-presenting (p < 0.001). Headaches, seizures and sensory deficits were the most frequent presenting symptoms in DAMA/PL patients, and 56.1% of those presenting with a seizure had a history of epilepsy. The most common documented reason for leaving was the duration of door-to-doctor time.ConclusionsYounger age, self-presenting mode of presentation and presentation with headache, seizures or sensory deficits are associated with premature leave or against-medical-advice discharge of patients with neurological complaints from the ED, and long waiting times were given as the major reason for leaving the ED. Increasing ED staff’s awareness of these factors and the optimization of pre-hospital assessment and demand management, thereby positively impacting on patient flow and ED process times, may help to prevent irregular discharges from the ED.
A prevalence survey of enteral parasites in preschool children in the Mangochi District of Malawi
Authors: Jones Timothy P. W. , Hart John D. , Kalua Khumbo , Bailey Robin L. 
Published: October 2019

Abstract

Background
Helminthic and protozoan infections are common, particularly in low- or middle-income countries. Although an association between parasite carriage and markers of poor growth have been shown in some studies, systematic reviews have suggested only a modest impact of clearing carriage. The prevalence of these pathogens and the effect that they have on growth in preschool children has never been investigated in Malawi.

Methods
One hundred ninety-three children aged 0–72 months were randomly recruited from rural villages in the Mangochi district of Malawi. Formol-ether concentration was performed on stool and the samples examined with a light microscope. Anthropometric data was taken for each child and the haemoglobin measured with a point of care test.

Results
The mean age of the children was 2 years 4 months. Overall prevalence of intestinal parasite infection was 37.3%. Protozoa were found in 28.5% of children, while helminths were found in 8.8%. The most commonly found organisms were Giardia lambia (12.4%), Entamoeba coli (10.4%) and Hookworm species (3.6%). Stunting was seen in 47.8% of children, 12.9% were underweight and 5.0% were wasted. No significant association was found between markers of poor growth and infection with any intestinal parasite.

Conclusions
We found that prevalence of helminth infection was low in preschool children living in the Mangochi district compared to international standards. However a significant proportion of the preschool population are infected with protozoa, particularly Giardia lambia. In this cohort, despite a significant prevalence of stunting, helminth infection was not significantly associated with any markers of poor growth. The significance of protozoal carriage and contribution to growth restriction in this context creates further avenues for future research.