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1.
Heliyon ; 9(12): e22472, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38076145

ABSTRACT

Purpose: the aim of this paper is to analyze the evolution of understanding of hybrid telework, especially after the boom experienced in the global pandemic of COVID-19, which has given rise to new ways of working. Design: /methodology/approach: in this study, bibliometrics and scientific mapping were used to analyze the conceptual structure of hybrid telework based on 104 documents extracted from the Web of Science (WoS) database. Thanks to the co-word analysis performed with SciMAT, the main themes were mapped, and the evolution, importance and relevance of terms related to hybrid telework were identified. Findings: the body of research literature about hybrid telework is underdeveloped even though it is the most valued option of telework, both by organizations and employees. There is a lack of published studies in the public sphere and in such relevant fields as occupational health. Practical implications: this study is the first bibliometric analysis conducted for hybrid telework and demonstrates how hybrid telework is key for organizations to manage the emerging challenges in this field: new preferences from employment candidates, occupational health, etc, and how important it is to have a proper management of hybrid telework in organizations. Originality/value: this study explores in detail the evolution of hybrid telework, an underexplored telework modality, given its growth as a mode of work as a consequence of the COVID-19 pandemic. It reveals critical points, dilemmas, paradoxes, and research gaps.

2.
Front Psychol ; 14: 1154578, 2023.
Article in English | MEDLINE | ID: mdl-36910822

ABSTRACT

[This corrects the article DOI: 10.3389/fpsyg.2022.1081595.].

3.
Front Psychol ; 14: 1140972, 2023.
Article in English | MEDLINE | ID: mdl-36844358

ABSTRACT

Introduction: The aim of this article is to understand the importance of internal audit departments todays-part of corporate governance and guardian of the organisation's culture and climate-, as well as the opportunities that new technologies offer to increase their effectiveness and efficiency. Methods: To this end, based on an exhaustive review of the literature, the concepts of internal audit and data analytics are related, and a framework is proposed for the implementation of a technology of these characteristics in an internal audit department. Results: The results of the research show that those companies that invest resources in readapting their processes to technological change are likely to obtain better results than those organisations that keep their management procedures obsolete. Discussion: Based on these results, it is concluded that there is a need to consider technological change in internal audit departments, specifically data analytics, to increase the effectiveness and efficiency of audit processes.

4.
Front Psychol ; 13: 1081595, 2022.
Article in English | MEDLINE | ID: mdl-36533011

ABSTRACT

The new paradigms that are emerging because of technological and social advances derived from the massive use of information and communication technologies (ICTs) are generating a transformative process that is modifying all economic sectors, and education is no exception. Higher Education Institutions (HEIs) are carrying out such transformation, reacting to the need of adaptation to this new reality, experiencing a complete cultural change that is challenging the attitudes, actions and values shared by the members and stakeholders of these organizations. In order to analyze the scientific literature about this topic, a bibliometric analysis has been carried out covering the period 1900-2021, considering a sample of 469 articles included in the Web of Science (WoS) database. The results show the multidisciplinary nature of the topic, including articles published in different areas, as well as its close link with aspects such as innovation, governance and agile methodologies. Finally, this study highlights the main lines of research that could attract more attention in the immediate future.

5.
Article in English | MEDLINE | ID: mdl-34065338

ABSTRACT

The COVID-19 pandemic has had an unprecedented impact on the labor market. The psychological pressure and uncertainty caused by the current changing workplace environment have led to negative consequences for workers. Considering the predictive relationship between employee engagement and wellbeing and in light of this unprecedented situation that affects workers of all the industries worldwide, this study aims to identify the key main drivers of employee engagement that can lead to employee wellbeing in the current context. Through a literature review, a theoretical model to strengthen engagement in times of COVID-19 is proposed. The main factors are conciliation, cultivation, confidence, compensation, and communication. Whereas prior to the pandemic, firms had already understood the need to achieve this, it is now considered a vital tool for staff health and wellbeing. This article makes two main contributions. First, it provides a model for boosting employee engagement, and therefore, wellbeing. Second, managerial suggestions are made to apply the theoretical model.


Subject(s)
COVID-19 , Work Engagement , Humans , Pandemics , SARS-CoV-2 , Workplace
6.
Eur J Hosp Pharm ; 28(4): 212-216, 2021 07.
Article in English | MEDLINE | ID: mdl-34162672

ABSTRACT

OBJECTIVE: To perform a cost-effectiveness and budget impact analysis from the perspective of the Spanish public healthcare system (SHS) to compare the number of overnight hospital stays avoided under a community and a hospital pharmacy model due to the administration of intravenous anti-infective therapy (IVAT) at a nursing home with 145 beds. METHODS: Analytical, observational, retrospective cohort study of a nursing home in Galicia (north-west Spain) that switched from a community to a hospital pharmaceutical management model. We compared the number of IVAT administrations, the number of hospital transfers and stays avoided, and mean annual costs avoided by the SHS before and after the switch. Costs were calculated using official SHS rates. RESULTS: The switch from the community to the hospital pharmacy model resulted in 2.8 more IVAT administrations (95% CI, 2.71 to 2.88) and 20.79 fewer overnight hospital stays (95% CI, 20.07 to 21.51) per 100 nursing home beds a month (p<0.001). The net monthly avoided cost for the SHS was 9971.52 €2019. The budget impact analysis showed that implementation of this model throughout Galicia and Spain would respectively avoid costs of 13.78 and 221.21 million €2019 a year. CONCLUSIONS: Hospital pharmacy models can contribute to a better optimisation of public healthcare resources and help improve the sustainability of the SHS.


Subject(s)
Budgets , Nursing Homes , Administration, Intravenous , Humans , Pharmaceutical Preparations , Retrospective Studies
7.
Int J Hosp Manag ; 92: 102733, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33106721

ABSTRACT

The rapid spatial diffusion of the COVID-19 epidemic outbreak has resulted in the total economic disruption of the Tourism Supply Chain (TSC) causing a significant reduction in revenue and creating liquidity issues for all operators. Firms in TSC are linked to each other in complex patterns, leading one risk to another. The purpose of this article is to understand the role of relationship management between hotel chains and their key TSC agents in order to overcome economic disruptions caused by epidemic outbreaks. Among the main contributions of this article are the identification of governments, tour operators, and competitors as the key relationships to be managed by hospitality firms. In addition, key areas for coordination with these actors are explored. Finally, the objectives of relationship management according to the partner are also addressed.

8.
Front Psychol ; 11: 1754, 2020.
Article in English | MEDLINE | ID: mdl-32793074

ABSTRACT

In the current digital era, the borders amongst firms are getting blurred when it comes to value creation. Therefore, the traditional configuration of the value chain is frequently replaced by other ones which include the collaborative participation of different agents. Within this context, global value chains, where the value activities are located in different countries, and industrial clusters, which combine competition and cooperation, are attracting a growing attention of both business leaders and scholars in the recent years. Through a bibliometric analysis, this paper disentangles the intellectual and conceptual structure of the research topic of industrial clusters and global value chains. Results show the multidisciplinary character of the topic, including papers published in different areas, such as business, regional studies and world development, as well as its close link with aspects like innovation, regional development, governance or organization. Finally, this study remarks the research lines that could attract more attention in the immediate future.

9.
Article in English | MEDLINE | ID: mdl-32187973

ABSTRACT

The study of work-life balance has undergone significant development in recent years as a result of changes in society and the growing importance of human resources (HR) for companies. Taking into account that human capital represents a critical success factor for businesses, the current context requires the development and implementation of HR management strategies aimed at attracting and retaining the most talented workers in order to obtain the expected results. The objective of this paper is to present an integrated model of work-life balance strategies, including the impacts of the different policies and practices on the retention of talented HR, which can be a basis for further academic developments on this subject, as well as a roadmap for managers. Hence, we will analyze a case study carried out in a multinational company-a leader in the technology and tourism sectors, and importantly dependent on valuable human capital, for which the HR strategy aims to improve the performance of the firm in the medium and long term through analysis, planning, and flexibility.


Subject(s)
Personnel Management , Personnel Turnover , Work-Life Balance , Health Resources , Humans , Workforce
10.
Inmunología (1987) ; 30(4): 108-114, oct.-dic. 2011. ilus, tab
Article in English | IBECS | ID: ibc-108934

ABSTRACT

Objectives: The LILRB1 gene has recently been associated with rheumatoid arthritis (RA)susceptibility in HLA-DRB1-shared epitope (SE) negative Japanese individuals. Since the contribution of the LILRB1 polymorphism to RA susceptibility may vary among ethnic populations, we examined this association in a group of Caucasian patients. The frequency ofLILRB1 alleles was also determined in patients according to the presence of DRB1-SE. Methods: Samples from 103 RA patients and 107 healthy controls were randomly collected. Polymorphism of the LILRB1 gene was analyzed by sequencing with primers that amplifiedintron 3 and exon 4.Results: The frequencies of LILRB1 alleles in RA patients did not differ from those of controls. However, when patients and controls were grouped according to SE, the PE-01/01 genotype was less frequent in negative-SE patients than in controls. Whereas SE is associated with higher anti-CCP antibody levels, as expected, the production of anti-CCP antibodies was lower in negative-SE patients with PE-01/01 genotype. Moreover, radiographic damage in hand and feet of SE-negative PE-01/01 patients was less severe than in patients with other genotypes. Conclusions: The participation of this LILRB1 polymorphism in the RA pathogenesis of this Caucasian cohort differed from that reported in a Japanese sample. Our findings suggest that the LILRB1-PE-01/01 genotype could exert a protective role in RA susceptibility and disease severity in the absence of SE (AU)


Objetivos: El gen LILRB1 se ha asociado a la susceptibilidad a desarrollar artritis reumatoide(AR) en aquellos individuos japoneses negativos para el epítopo compartido del HLA-DRB1.Dado que la contribución del polimorfismo en LILRB1 a la susceptibilidad a desarrollar artritis reumatoide puede variar según las distintas etnias, hemos examinado esta asociación con la artritis reumatoide en un grupo de pacientes caucásicos. La frecuencia de los alelosLILRB1 fue también determinada en los pacientes clasificados según la presencia del epítopo compartido. Métodos: Se recogieron al azar muestras de 103 pacientes de AR y 107 controles sanos. El polimorfismo en el gen LILRB1 se analizó con cebadores que amplificaban el intrón 3 y elexón 4.Resultados: Las frecuencias diploides de los alelos de LILRB1 en los pacientes de artritis reumatoide no diferían de la de los controles. Sin embargo, cuando los pacientes y controles se agruparon según la presencia del epítopo compartido, la frecuencia del genotipo PE-01/01fue menor en los pacientes con epítopo compartido negativo que en controles con epítopo compartido negativo. Mientras que el epítopo compartido se asoció con niveles altos de anticuerpos anti-CCP, la producción de anticuerpos anti-CCP fue menor en pacientes con epítopo compartido negativo y genotipo PE-01/01. Además, el daño radiográfico en manos y pies en pacientes con epítopo compartido negativo y genotipo PE-01/01 fue menos severa que en pacientes con otros genotipos. Conclusiones: La participación del polimorfismo del LILRB1 en la fisiopatogenia de la AR en esta cohorte de pacientes Caucásicos difiere de la publicada en los pacientes japoneses. Nuestros resultados sugieren que el genotipo LILRB1-PE-01/01 puede ejercer un papel en la susceptibilidad de la AR y en la severidad de la misma en ausencia del epítopo compartido (AU)


Subject(s)
Humans , Arthritis, Rheumatoid/genetics , HLA-DRB1 Chains/genetics , Polymorphism, Genetic/genetics
11.
Medicine (Baltimore) ; 89(1): 47-52, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20075704

ABSTRACT

A new autoantibody against a 155-kDa protein has been described in patients with myositis. We conducted a study to determine the occurrence and types of cancer occurring in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and analyzed the value of this autoantibody as a serologic marker of cancer-associated myositis (CAM). Serum samples from all patients were examined by protein immunoprecipitation assays with HeLa cells to determine the presence of a 155-kDa protein band. HLA-DRB1 and DQA1 typing was performed by polymerase chain reaction-reverse sequence specific oligonucleotide. Statistical analyses were carried out with the Mann Whitney U and Fisher exact tests. Associations were determined using odds ratios (ORs) with 95% confidence intervals (CI). Eighty-five patients with myositis (20 PM and 65 DM) were included. CAM was detected in 16 patients (19%), 14 with DM. The shawl sign rash was significantly more frequent in patients with CAM than in those without (p < 0.01). Adenocarcinoma was the most frequent type of cancer (87.5%). Anti-p155 autoantibody was found in 1 of the 20 (5%) patients with PM and in 15 of the 65 (23%) patients with DM. A relationship between anti-p155 and CAM was found in DM patients (OR, 23; 95% CI, 5.23-101.2). The HLA-DQA1*0102 allele was not found in any of the anti-p155-positive patients. The prevalence of CAM in our cohort was 19%. Autoantibody against p155 was highly related to CAM and could be a reliable marker of cancer in patients with DM.


Subject(s)
Autoantibodies/blood , Myositis/blood , Myositis/immunology , Female , Humans , Male , Middle Aged
12.
Rheumatology (Oxford) ; 48(6): 676-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19386818

ABSTRACT

OBJECTIVE: To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKAs) in a cohort of patients with idiopathic inflammatory myopathy. METHODS: In a cross-sectional study, we determined the presence of anti-CCP and AKAs by ELISA and IIF, respectively, in a cohort of 90 consecutive patients with idiopathic inflammatory myopathy. Associations between anti-CCP and clinical manifestations or other autoantibodies were determined with the chi-square and Mann-Whitney U-tests. Radiographs of hands were retrospectively evaluated. Serum autoantibody profile was determined in all patients. RESULTS: Twelve patients were positive to anti-CCP (13.3%); in eight cases values were moderate-high. AKAs were not detected in any patient. Comparison between patients positive and negative to anti-CCP did not show clinical or biological differences. Arthritis joint erosions or positive status to anti-synthetase antibodies were not more frequent in patients with anti-CCP antibodies. Prevalence of RF was the only variable significantly associated with the presence of these antibodies (P = 0.043). CONCLUSIONS: High titres of anti-CCP can occasionally be found in patients with inflammatory myopathy. Therefore, a possible diagnosis of RA should be considered with caution in these patients.


Subject(s)
Autoantibodies/blood , Keratins/immunology , Myositis/immunology , Peptides, Cyclic/immunology , Aged , Biological Factors/blood , Chi-Square Distribution , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , False Positive Reactions , Female , Fluorescent Antibody Technique, Indirect , Hand/diagnostic imaging , Humans , Male , Middle Aged , Myositis/diagnostic imaging , Radiography , Rheumatoid Factor/analysis , Statistics, Nonparametric
13.
Exp Hematol ; 36(1): 69-77, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17959301

ABSTRACT

OBJECTIVE: Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism in the clinical activity of rituximab for treatment of B-cell malignancies. Natural killer (NK) cells, through the activating receptor FcgammaRIIIa (CD16), play a major role in rituximab-mediated ADCC. We have studied the in vitro effect of NK stimulators, such as interleukin-15 (IL-15) and CpG oligodeoxynucleotides A-Class (CpG ODN A), in the enhancement of rituximab-mediated ADCC against B-cell lymphoma. METHODS: Peripheral blood mononuclear cells (PBMC), purified NK cells, or NK-depleted PBMC from healthy donors, were activated with IL-15 or CpG ODN A, and cocultured with B-lymphoma cells in the presence of rituximab to evaluate the enhancement of the cytotoxicity. RESULTS: The rituximab-mediated ADCC of IL-15-activated PBMC was twofold compared to unstimulated PBMC (73% +/- 7% vs 37% +/- 5% respectively, p < 0.001). Similarly, rituximab-mediated ADCC was enhanced when PBMC were activated with CpG ODN A as compared to CpG ODN control (61% +/- 11% vs 36% +/- 8%, respectively, p = 0.02). Nevertheless, the ADCC of purified NK cells was increased only with IL-15. NK-depleted PBMC activated with either IL-15 or CpG ODN A showed no ADCC, suggesting that NK are the major effector cells. Furthermore, IL-15 or CpG ODN A-activated PBMC, but not activated purified NK cells, secreted large amounts of interferon-gamma in the presence of rituximab-coated lymphoma cells. CONCLUSIONS: IL-15 and CpG ODN A enhance rituximab-mediated ADCC against B-cell lymphoma. Under these conditions, NK cells seem to be the main effector cells mediating ADCC. These findings suggest that these agents could be used as adjuvants in combination with rituximab for patients with B-cell lymphoma.


Subject(s)
Adjuvants, Immunologic/pharmacology , Antibodies, Monoclonal/pharmacology , Antibody-Dependent Cell Cytotoxicity/drug effects , Burkitt Lymphoma/pathology , Interleukin-15/pharmacology , Killer Cells, Natural/drug effects , Leukocytes, Mononuclear/drug effects , Oligodeoxyribonucleotides/pharmacology , Adjuvants, Immunologic/administration & dosage , Adult , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal, Murine-Derived , Cell Line, Tumor/drug effects , Drug Synergism , Humans , Interferon-gamma/biosynthesis , Interleukin-15/administration & dosage , Killer Cells, Natural/immunology , Leukocytes, Mononuclear/immunology , Lymphocyte Activation/drug effects , Oligodeoxyribonucleotides/administration & dosage , Rituximab , Toll-Like Receptor 9/agonists
14.
Leuk Lymphoma ; 46(3): 435-42, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15621835

ABSTRACT

Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors that have been implicated in tumoral transformation, especially in hematological malignancies. Because of this, the JAK/STAT pathway is attractive as a therapeutic target in these tumors. In the present study, we analyzed the ability of fludarabine and two JAK kinase inhibitors, AG490 and WHI-P131, to block STAT1 activation and induce apoptosis on B-cell chronic lymphocytic leukemia (B-CLL) cells. All drugs were able to induce a high percentage of apoptosis on B-CLL cells from all patients studied. However, only AG490 and WHI-P131 were able to strongly suppress the STAT1 activation of B-CLL cells. In conclusion, our data show that JAK kinase inhibitors, such as AG490 and WHI-P131 are able to inhibit the STAT1 pathway on B-CLL cells and are strong inductors of apoptosis on these cells.


Subject(s)
Apoptosis/drug effects , DNA-Binding Proteins/physiology , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Protein-Tyrosine Kinases/antagonists & inhibitors , Quinazolines/pharmacology , Trans-Activators/physiology , Tyrphostins/pharmacology , Vidarabine/analogs & derivatives , Vidarabine/pharmacology , Aged , Aged, 80 and over , Cell Survival/drug effects , DNA-Binding Proteins/antagonists & inhibitors , Electrophoretic Mobility Shift Assay , Female , Flow Cytometry , Humans , Interferon-gamma/pharmacology , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , STAT1 Transcription Factor , Signal Transduction/drug effects , Signal Transduction/physiology , Time Factors , Trans-Activators/antagonists & inhibitors , Tumor Cells, Cultured
15.
Leuk Lymphoma ; 45(11): 2307-14, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15512822

ABSTRACT

B-cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy characterized by the accumulation of mature CD5+ B lymphocytes with a defective apoptosis. A subset of blood monocyte-derived adherent cells generated in vitro protects B-CLL cells from apoptosis playing a role as nurse-like cells (NLCs). Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine; F-ara-A) is an adenine nucleoside analog used to treat B-CLL. To gain insight into the mechanisms implicated in the antitumoral effect of fludarabine in B-CLL cells, we performed cross-cultures with B-CLL cells and NLCs treated and untreated with fludarabine. Our results showed that fludarabine blocked the development of NLCs and induced apoptosis in these cells when they were present in culture. Moreover, CD19+/CD5+B-CLL cells treated with fludarabine underwent apoptosis and this event was not related with the presence of NLCs whether treated or not with fludarabine. In conclusion, apoptosis induced by fludarabine in CD19+/CD5+B-CLL cells was due to a direct effect on these cells and not due to its effect in the NLCs.


Subject(s)
Antigens, CD19/biosynthesis , Antineoplastic Agents/pharmacology , Apoptosis , CD5 Antigens/biosynthesis , Leukemia, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Vidarabine/analogs & derivatives , Vidarabine/pharmacology , Aged , Annexin A5/pharmacology , Cell Death , Cell Survival , Female , Flow Cytometry , Humans , Immunophenotyping , Leukemia, B-Cell/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Monocytes/cytology , Time Factors
16.
Autoimmunity ; 36(5): 275-83, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14567557

ABSTRACT

Neonatal thymectomy (NTx) in mice induces a group of alterations in the immune system homeostasis that results in the development of a variety of organ-specific autoimmune diseases such as gastritis, thyroiditis, oophoritis and orchitis. Given the importance of self-antigen expression in thymus for the control of autoreactive cells and generation of regulatory cells, we have compared the expression of parietal cell antigen in two strains of mice with the same H-2: BALB/c (susceptible to develop gastritis after NTx) and DBA/2 (resistant). We detected mRNA of HK-ATPase alpha and beta chains in day 1 thymi of both strains. Fifty percent of BALB/c mice presented mRNA levels similar to DBA/2. However, lower mRNA levels were found in the remaining BALB/c mice that may correspond to those that would develop AIG after NTx. Since the presence of the antigen in periphery is also necessary for the induction of regulatory cells, we have compared both strains observing in day 1 stomachs from resistant DBA/2 strain, a significantly higher content of positive cells for HK-ATPase subunits than stomachs from susceptible BALB/c strain. Also, the presence of antinuclear Abs in NTx BALB/c mice makes this model a useful experimental system for analyzing the responsible mechanisms breaking the non-specific self-tolerance.


Subject(s)
Autoantigens/metabolism , Autoimmune Diseases/immunology , Gastritis/immunology , H(+)-K(+)-Exchanging ATPase/immunology , H(+)-K(+)-Exchanging ATPase/metabolism , Parietal Cells, Gastric/immunology , Stomach/enzymology , Animals , Animals, Newborn , Antibodies, Antinuclear/blood , Autoantibodies/blood , Autoantigens/genetics , Autoimmune Diseases/enzymology , Autoimmune Diseases/genetics , Disease Models, Animal , Disease Susceptibility , Enzyme-Linked Immunosorbent Assay , Gastric Mucosa/immunology , Gastric Mucosa/pathology , Gastritis/enzymology , Gastritis/genetics , H(+)-K(+)-Exchanging ATPase/genetics , Immunity, Innate , Immunoglobulin G/blood , Mice , Mice, Inbred BALB C , Mice, Inbred DBA , RNA, Messenger/genetics , RNA, Messenger/metabolism , Stomach/pathology , Thymectomy
17.
J Biol Chem ; 278(50): 50641-4, 2003 Dec 12.
Article in English | MEDLINE | ID: mdl-14523012

ABSTRACT

The HB autoantigen, a 10-kDa DNA-binding protein recognized by autoantibodies only when bound to DNA, was identified by two-dimensional electrophoresis. Silver-stained protein spots corresponding to the antigen were excised from two-dimensional electrophoresis gels, digested with trypsin, and analyzed by matrix-assisted laser desorption/ionization-reflectron time of flight and nano-electrospray ionization-ion trap/mass spectrometry. Data base search identified the HB antigen as the barrier-to-autointegration factor, a cellular protein implicated in the cellular cycle that blocks autointegration and promotes intermolecular integration of retrovirus such as the Moloney murine leukemia and the human immunodeficiency type 1 virus. The physicochemical characteristics described for these proteins, their ability to bind double-stranded DNA but not single-stranded DNA, and their nuclear localization confirm that HB and barrier-to-autointegration factor are the same protein.


Subject(s)
Autoantigens/physiology , DNA-Binding Proteins/physiology , Nuclear Proteins/physiology , Amino Acid Sequence , Animals , Autoantigens/chemistry , Blotting, Western , Cell Line , Cell Nucleus/metabolism , DNA/chemistry , DNA/metabolism , DNA, Single-Stranded/genetics , DNA-Binding Proteins/chemistry , Databases as Topic , Electrophoresis, Gel, Two-Dimensional , Electrophoresis, Polyacrylamide Gel , HIV-1/genetics , Humans , Liver/metabolism , Mice , Microscopy, Fluorescence , Molecular Sequence Data , Moloney murine leukemia virus/genetics , Nuclear Proteins/chemistry , Protein Binding , Silver Staining , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Trypsin/pharmacology
18.
J Leukoc Biol ; 74(6): 998-1007, 2003 Dec.
Article in English | MEDLINE | ID: mdl-12972509

ABSTRACT

Umbilical cord blood (UCB) is now being considered an alternative to bone marrow for restoring hematopoiesis after myeloablative therapy. The lower risk of acute and chronic graft-versus-host disease in patients who received UCB cells seems related to the nature of UCB-T cells. Phenotypically, UCB-CD3+ cells are mostly naive (CD45RA+) and represent a transitional population between thymocytes and adult T cells. We examined the immune reactivity of highly purified, negatively selected CD4+CD45RA+ cells by mimicking activation via T cell receptor (TCR). All experiments included the extensively characterized adult peripheral blood (APB) cells as reference. On the contrary to APB, naive UCB-CD4+ cells were able to proliferate with anti-CD3 stimulation alone. With addition of interleukin (IL)-2 or costimulatory signal, both populations reached similar proliferation. Forty-eight hours after anti-CD3 stimulation, CD4+CD45RA+ from UCB, but not APB, showed characteristic blastic morphology and significant expression of CD25 on the surface. A low concentration of IL-2 was detected at 24 h by anti-CD3-stimulated UCB CD4+CD45RA+, which rapidly disappeared. By 72 h after activation, CD4+CD45RA+ UCB cells showed extensive apoptosis, whereas CD4+CD45RA+ APB cells showed low levels of apoptosis. Using RNase protection assay, we observed that CD95L levels were significantly higher in naive CD4+ cells from UCB than from APB after activation. However, neutralizing Fas-Fc protein was unable to inhibit anti-CD3-induced apoptosis, suggesting that this was a CD95-independent mechanism. These results indicate that UCB-CD4+CD45RA+ cells are able to start proliferating as a result of early IL-2 production after TCR engagement alone, but probably, as a result of the consumption of this IL-2, they undergo cell death.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Fetal Blood/cytology , Lymphocyte Activation/immunology , Receptors, Antigen, T-Cell/metabolism , Adult , Apoptosis , CD3 Complex/immunology , CD4 Antigens/metabolism , Cell Culture Techniques , Cell Division/immunology , Flow Cytometry , Humans , Interleukin-2/metabolism , Leukocyte Common Antigens/metabolism , Lymphocyte Activation/drug effects , Ribonuclease, Pancreatic/metabolism , Thymidine/metabolism
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