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1.
J Hematol Oncol ; 14(1): 148, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530889

RESUMO

BACKGROUND: Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. METHODS: Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. RESULTS: KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. CONCLUSIONS: KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.


Assuntos
Proteína Kangai-1/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica , Animais , Feminino , Proteína Kangai-1/genética , Masculino , Microdomínios da Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
2.
Proc Natl Acad Sci U S A ; 116(42): 20910-20916, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31570599

RESUMO

The doctoral advisor-typically the principal investigator (PI)-is often characterized as a singular or primary mentor who guides students using a cognitive apprenticeship model. Alternatively, the "cascading mentorship" model describes the members of laboratories or research groups receiving mentorship from more senior laboratory members and providing it to more junior members (i.e., PIs mentor postdocs, postdocs mentor senior graduate students, senior students mentor junior students, etc.). Here we show that PIs' laboratory and mentoring activities do not significantly predict students' skill development trajectories, but the engagement of postdocs and senior graduate students in laboratory interactions do. We found that the cascading mentorship model accounts best for doctoral student skill development in a longitudinal study of 336 PhD students in the United States. Specifically, when postdocs and senior doctoral students actively participate in laboratory discussions, junior PhD students are over 4 times as likely to have positive skill development trajectories. Thus, postdocs disproportionately enhance the doctoral training enterprise, despite typically having no formal mentorship role. These findings also illustrate both the importance and the feasibility of identifying evidence-based practices in graduate education.


Assuntos
Pessoal de Laboratório/educação , Competência Profissional , Pesquisa/educação , Adulto , Educação de Pós-Graduação , Feminino , Humanos , Pessoal de Laboratório/psicologia , Estudos Longitudinais , Masculino , Estados Unidos , Adulto Jovem
3.
J Contin Educ Health Prof ; 37(1): 19-26, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28125502

RESUMO

INTRODUCTION: The importance of training for Hospice and Palliative Care (HPC) professionals has been increasing with the systemization of HPC in Korea. Hence, the need and importance of training quality for HPC professionals are growing. This study evaluated the construct validity and reliability of the Evaluation Indicators for standard Hospice and Palliative Care Training (EIHPCT) program. METHODS: As a framework to develop evaluation indicators, an invented theoretical model combining Stufflebeam's CIPP (Context-Input-Process-Product) evaluation model with PRECEDE-PROCEED model was used. To verify the construct validity of the EIHPCT program, a structured survey was performed with 169 professionals who were the HPC training program administrators, trainers, and trainees. To examine the validity of the areas of the EIHPCT program, exploratory factor analysis and confirmatory factor analysis were conducted. RESULTS: First, in the exploratory factor analysis, the indicators with factor loadings above 0.4 were chosen as desirable items, and some cross-loaded items that loaded at 0.4 or higher on two or more factors were adjusted as the higher factor. Second, the model fit of the modified EIHPCT program was quite good in the confirmatory factor analysis (Goodness-of-Fit Index > 0.70, Comparative Fit Index > 0.80, Normed Fit Index > 0.80, Root Mean square of Residuals < 0.05). The modified model of the EIHPCT comprised 4 areas, 13 subdomains, and 61 indicators. DISCUSSION: The evaluation indicators of the modified model will be valuable references for improving the HPC professional training program.


Assuntos
Competência Clínica/normas , Cuidados Paliativos , Indicadores de Qualidade em Assistência à Saúde/normas , Desempenho Profissional/estatística & dados numéricos , Adulto , Estudos de Avaliação como Assunto , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/normas , Reprodutibilidade dos Testes , República da Coreia , Inquéritos e Questionários , Ensino/normas , Recursos Humanos
4.
Asian Pac J Cancer Prev ; 17(7): 3301-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27509967

RESUMO

BACKGROUND: Cancer is a leading cause of death in Korea. To prevent cancer, it is essential to facilitate and promote appropriate cancer screening behavior in the adult population. The aim of this study was to examine health beliefs related to cancer screening intentions using the Health Belief Model (HBM). MATERIALS AND METHODS: The research participants comprised 275 male health and safety managers at commercial companies in Korea. The selfadministered survey explored demographic characteristics, cancerrelated factors, beliefs about cancer/cancer screening (BCCS) (vulnerability to cancer, severity of cancer, benefits of screening, and barriers to screening), and cancer screening intention. Multivariate logistic regression analyses were used to identify factors associated with an intention to be screened for cancer. RESULTS: Perceived health status and need for cancer prevention education were major factors associated with BCCS. Poorer health status was associated with greater perceived vulnerability, a perception of fewer benefits, and more barriers (p<0.05). A perceived greater need for cancer prevention education was associated with a higher perceived severity of cancer and more perceived barriers to screening (p<0.05). Marital status, cancer screening experience, and perceived vulnerability to cancer were significant influences on the cancer screening intention (p<0.05). Participants who had undergone cancer screening in the past 2 years were more likely to intend to be screened for cancer than were those who had not been screened; this was true across all degrees of intention and all types of cancer (p<0.01). Hesitant people considered themselves less vulnerable to gastric, lung, and liver cancer than did the poeple who intended to undergo cancer screening (p<0.05). CONCLUSIONS: Based on our findings, we recommend that workplace cancer prevention programs attempt to increase awareness about vulnerability to cancer among workers who hesitate to undergo cancer screening.


Assuntos
Detecção Precoce de Câncer/psicologia , Comportamentos Relacionados com a Saúde/fisiologia , Neoplasias/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adulto , Educação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Intenção , Masculino , Percepção , República da Coreia
5.
Cardiovasc Ther ; 34(4): 245-53, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27214098

RESUMO

AIM: Various methods are used to augment the efficacy of cell therapy in myocardial infarction (MI). In this study, we used the "activated platelet supernatant (APS)" to prime autologous "granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells ((mob) PBMCs)" and investigated the efficacy of cell-based therapy in MI. METHOD: Rat (mob) PBMCs were isolated after daily subcutaneous injections of G-CSF at 100 µg/kg for 3 days. APS was isolated separately after activating rat platelets with thrombin 0.5 U/mL for 2 hours. Priming was performed with APS for 6 hours. To check the paracrine effect of primed (mob) PBMCs, we used the 36-hour culture supernatant of the primed cells. A rat MI model was used for an in vivo model. RESULT: Cytokines such as IL-1ß, IL-10, and TGFß were 3.7±0.9-fold, 3.4±1.2-fold, and 1.2±0.1-fold higher in APS, respectively, compared with naïve platelet supernatant. By APS priming, (mob) PBMCs showed M2 polarization and upregulation of angiogenic molecules (i.e., TEK, IL-10, CXCL1, and CX3CR1). APS-primed (mob) PBMCs had a 2.3-fold increased adhesion ability, induced by upregulated integrins. Rat endothelial cells cultured in the 36-hour culture supernatant of APS-primed (mob) PBMCs showed a 1.6-fold augmented proliferation and capillary network formation. In vivo transplantation of APS-primed (mob) PBMCs into rat MI models showed a significant trend of reduction in fibrosis area (P=.001) and wall thinning (P=.030), which lead to improvement in cardiac function measured by echocardiography. CONCLUSION: Our data reveal that APS priming can enhance the wound-healing potential of (mob) PBMCs. APS priming may be a promising method for cell-based therapy of MI.


Assuntos
Plaquetas/metabolismo , Leucócitos Mononucleares/transplante , Infarto do Miocárdio/cirurgia , Comunicação Parácrina , Ativação Plaquetária , Proteínas Angiogênicas/metabolismo , Animais , Moléculas de Adesão Celular/metabolismo , Proliferação de Células , Células Cultivadas , Citocinas/sangue , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Injeções Subcutâneas , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica , Fenótipo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Frações Subcelulares/metabolismo , Fatores de Tempo , Cicatrização
6.
PLoS One ; 11(5): e0155396, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27171430

RESUMO

The arginine repressor (ArgR) is an arginine-dependent transcription factor that regulates the expression of genes encoding proteins involved in the arginine biosynthesis and catabolic pathways. ArgR is a functional homolog of the arginine-dependent repressor/activator AhrC from Bacillus subtilis, and belongs to the ArgR/AhrC family of transcriptional regulators. In this research, we determined the structure of the ArgR (Bh2777) from Bacillus halodurans at 2.41 Å resolution by X-ray crystallography. The ArgR from B. halodurans appeared to be a trimer in a size exclusion column and in the crystal structure. However, it formed a hexamer in the presence of L-arginine in multi-angle light scattering (MALS) studies, indicating the oligomerization state was dependent on the presence of L-arginine. The trimeric structure showed that the C-terminal domains form the core, which was made by inter-subunit interactions mainly through hydrophobic contacts, while the N-terminal domains containing a winged helix-turn-helix DNA binding motif were arranged around the periphery. The arrangement of trimeric structure in the B. halodurans ArgR was different from those of other ArgR homologs previously reported. We finally showed that the B. halodurans ArgR has an arginine-dependent DNA binding property by an electrophoretic mobility shift assay.


Assuntos
Arginina/metabolismo , Bacillus/genética , Bacillus/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Multimerização Proteica , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo , Transcrição Gênica , Sequência de Aminoácidos , DNA Bacteriano/metabolismo , Regulação Bacteriana da Expressão Gênica , Modelos Moleculares , Ligação Proteica , Homologia Estrutural de Proteína , Relação Estrutura-Atividade
7.
Cell Stem Cell ; 18(4): 508-21, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-26996598

RESUMO

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we examine the role of CD82/KAI1 in niche-mediated LT-HSC maintenance. We found that CD82/KAI1 is expressed predominantly on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs). In Cd82(-/-) mice, LT-HSCs were selectively lost as they exited from quiescence and differentiated. Mechanistically, CD82-based TGF-ß1/Smad3 signaling leads to induction of CDK inhibitors and cell-cycle inhibition. The CD82 binding partner DARC/CD234 is expressed on macrophages and stabilizes CD82 on LT-HSCs, promoting their quiescence. When DARC(+) BM macrophages were ablated, the level of surface CD82 on LT-HSCs decreased, leading to cell-cycle entry, proliferation, and differentiation. A similar interaction appears to be relevant for human HSPCs. Thus, CD82 is a functional surface marker of LT-HSCs that maintains quiescence through interaction with DARC-expressing macrophages in the BM stem cell niche.


Assuntos
Sistema do Grupo Sanguíneo Duffy , Células-Tronco Hematopoéticas , Proteína Kangai-1 , Macrófagos , Receptores de Superfície Celular , Animais , Feminino , Humanos , Masculino , Camundongos , Sistema do Grupo Sanguíneo Duffy/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Proteína Kangai-1/biossíntese , Proteína Kangai-1/deficiência , Proteína Kangai-1/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores de Superfície Celular/metabolismo
8.
Acta Crystallogr F Struct Biol Commun ; 71(Pt 3): 291-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25760703

RESUMO

The arginine repressor (ArgR) is a transcriptional regulator which regulates genes encoding proteins involved in arginine biosynthesis and the arginine catabolic pathway. ArgR from the alkaliphilic bacterium Bacillus halodurans was cloned and overexpressed in Escherichia coli. ArgR (Bh2777) from B. halodurans is composed of 149 amino-acid residues with a molecular mass of 16 836 Da. ArgR was crystallized at 296 K using 1,2-propanediol as a precipitant. Crystals of N-terminally His-tagged ArgR were obtained by the sitting-drop vapour-diffusion method. Dehydrated crystals showed a dramatic improvement in diffraction quality and diffracted to 2.35 Šresolution. The crystals belonged to the cubic space group I23, with unit-cell parameters a = b = c = 104.68 Å. The asymmetric unit contained one monomer of ArgR, which generates a trimer by the threefold axis of the space group, giving a crystal volume per mass (VM) of 2.98 Å(3) Da(-1) and a solvent content of 56.8%.


Assuntos
Bacillus/química , Proteínas de Bactérias/química , Proteínas Repressoras/química , Proteínas de Bactérias/isolamento & purificação , Cromatografia em Gel , Cristalização , Cristalografia por Raios X , Proteínas Repressoras/isolamento & purificação
9.
Asian Pac J Cancer Prev ; 16(2): 501-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25684478

RESUMO

BACKGROUND: To evaluate the effectiveness of the National Train-the-Trainers Program for Hospice and Palliative Care Experts (TTHPC) sponsored by the National Cancer Center of Korea between 2009 and 2012. This program was developed to improve the teaching skills of those in the field of hospice and palliative care (HPC). MATERIALS AND METHODS: Training was offered in eight 1-day sessions between 2009 and 2012. The effect of the program was measured using Kirkpatrick's model of educational outcomes. First, levels 1 and 2 were evaluated immediately after the 1-day program (n=120). In 2012, the level-3 evaluation test was administered to trainers who offered at least one HPC training (n=78) as well as to their trainees (n=537). RESULTS: The level-1 evaluation addressed participant reactions to and satisfaction with the program. Participants (n=120) were generally satisfied with the content, the method, and the overall course (mean range: 3.94-4.46 on a five-point Likert scale). The level-2 evaluation (learning) showed that participants gained knowledge and confidence related to teaching HPC (4.24 vs. 4.00). The level-3 evaluation (behavioral), which assessed trainers' application of teaching skills to HPC, showed that trainees rated the teaching methods of trainers (mean range: 4.03-4.08) more positively than did trainers (p<0.05). Female trainers were more likely than were male trainers to plan sessions in consideration of their trainees' characteristics (4.11 vs. 3.58; p<0.05), and nurse trainers were more likely than physician trainers to use a variety of instructional methods (4.05 vs. 3.36; p<0.05) CONCLUSIONS: We conducted systematic evaluations based on Kirkpatrick's model to assess the effectiveness of our train-the- trainers program. Our educational program was practical, effective, and followed by our HPC experts, who needed guidance to learn and improve their clinical teaching skills.


Assuntos
Currículo/normas , Pessoal de Saúde/educação , Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Ensino
10.
Cardiovasc Res ; 104(1): 171-82, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25082847

RESUMO

AIMS: From our previous clinical trials, intracoronary infusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells ((mob)PBMCs) proved to be effective in improving myocardial contractility and reducing infarct volume in acute myocardial infarction. We tested the effect of priming (mob)PBMCs with erythropoietin (EPO) to augment its therapeutic efficacy. METHODS AND RESULTS: (mob)PBMCs were obtained from healthy volunteers after a 3-day subcutaneous injection of G-CSF (10 µg/kg). About 40% of (mob)PBMCs were EPO receptor (EPOR) (+) and responded to 6 h EPO-priming (10 IU/mL) by increasing the expression of vasculogenic factors (i.e. IL8, IL10, bFGF, PDGF, MMP9) and adhesion molecules (i.e. integrin αV, ß1, ß2, ß8) through the JAK2 and Akt pathway. These responses were also observed in PBMCs from elderly patients with coronary disease. The conditioned media from EPO-primed (mob)PBMCs contained various cytokines such as IL8, IL10, TNFα, and PDGF, which enhanced the migration and tube formation capability of endothelial cells. EPO-primed (mob)PBMCs also showed increased adhesion on endothelial cells or fibronectin. Augmented vasculogenic potential of EPO-primed (mob)PBMCs was confirmed in a Matrigel plug assay, ischaemic hindlimb, and myocardial infarction models of athymic nude mice. There were two action mechanisms: (i) cellular effects confirmed by direct incorporation of human (mob)PBSCs into mouse vasculature and (ii) indirect humoral effects confirmed by the therapeutic effect of the supernatant of EPO-primed (mob)PBMCs. CONCLUSION: Brief ex vivo EPO-priming is a novel method to augment the vasculogenic potential of human (mob)PBMCs, which would help to achieve better results after intracoronary infusion in myocardial infarction patients.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Eritropoetina/farmacologia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Leucócitos Mononucleares/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Proteínas Angiogênicas/metabolismo , Animais , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Doença da Artéria Coronariana/sangue , Meios de Cultivo Condicionados/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Membro Posterior , Humanos , Injeções Subcutâneas , Isquemia/metabolismo , Isquemia/fisiopatologia , Isquemia/cirurgia , Janus Quinase 2/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/transplante , Masculino , Camundongos Nus , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/cirurgia , Transplante de Células-Tronco de Sangue Periférico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Recombinantes/farmacologia , Regeneração , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
11.
J Mol Cell Cardiol ; 75: 64-75, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25016235

RESUMO

Platelets not only play a role in hemostasis, but they also promote angiogenesis and tissue recovery by releasing various cytokines and making an angiogenic milieu. Here, we examined autologous 'activated platelet supernatant (APS)' as a priming agent for stem cells; thereby enhance their pro-angiogenic potential and efficacy of stem cell-based therapy for ischemic diseases. The mobilized peripheral blood stem cells ((mob)PBSCs) were isolated from healthy volunteers after subcutaneous injection of granulocyte-colony stimulating factor. APS was collected separately from the platelet rich plasma after activation by thrombin. (mob)PBSCs were primed for 6h before analysis. Compared to naive platelet supernatants, APS had a higher level of various cytokines, such as IL8, IL17, PDGF and VEGF. APS-priming for 6h induced (mob)PBSCs to express key angiogenic factors, surface markers (i.e. CD34, CD31, and CXCR4) and integrins (integrins α5, ß1 and ß2). Also (mob)PBSCs were polarized toward CD14(++)/CD16(+) pro-angiogenic monocytes. The priming effect was reproduced by an in vitro reconstruction of APS. Through this phenotype, APS-priming increased cell-cell adhesion and cell-extracellular matrix adhesion. The culture supernatant of APS-primed (mob)PBSCs contained high levels of IL8, IL10, IL17 and TNFα, and augmented proliferation and capillary network formation of human umbilical vein endothelial cells. In vivo transplantation of APS-primed (mob)PBSCs into athymic mice ischemic hindlimbs and Matrigel plugs elicited vessel differentiation and tissue repair. In safety analysis, platelet activity increased after mixing with (mob)PBSCs regardless of priming, which was normalized by aspirin treatment. Collectively, our data identify that APS-priming can enhance the angiogenic potential of (mob)PBSCs, which can be used as an adjunctive strategy to improve the efficacy of cell therapy for ischemic diseases.


Assuntos
Plaquetas/metabolismo , Células da Medula Óssea/citologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Animais , Plaquetas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Citocinas/metabolismo , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Comunicação Parácrina/efeitos dos fármacos , Fenótipo , Regeneração/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Trombose/patologia
12.
Mol Ther ; 22(8): 1518-1529, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24736277

RESUMO

Emerging studies suggested that murine podoplanin-positive monocytes (PPMs) are involved in lymphangiogenesis. The goal of this study was to demonstrate the therapeutic lymphangiogenesis of human PPMs by the interaction with platelets. Aggregation culture of human peripheral blood mononuclear cells (PBMCs) resulted in cellular aggregates termed hematospheres. During 5-day culture, PPMs expanded exponentially and expressed several lymphatic endothelial cell-specific markers including vascular endothelial growth factor receptor (VEGFR)-3 and well-established lymphangiogenic transcription factors. Next, we investigated the potential interaction of PPMs with platelets that had C-type lectin-like receptor-2 (CLEC-2), a receptor of podoplanin. In vitro coculture of PPMs and platelets stimulated PPMs to strongly express lymphatic endothelial markers and upregulate lymphangiogenic cytokines. Recombinant human CLEC-2 also stimulated PPMs through Akt and Erk signaling. Likewise, platelets in coculture with PPMs augmented secretion of a lymphangiogenic cytokine, interleukin (IL)-1-ß, via podoplanin/CLEC-2 axis. The supernatant obtained from coculture was able to enhance the migration, viability, and proliferation of lymphatic endothelial cell. Local injection of hematospheres with platelets significantly increased lymphatic neovascularization and facilitated wound healing in the full-thickness skin wounds of nude mice. Cotreatment with PPMs and platelets augments lymphangiogenesis through podoplanin/CLEC-2 axis, which thus would be a promising novel strategy of cell therapy to treat human lymphatic vessel disease.


Assuntos
Plaquetas/metabolismo , Técnicas de Cocultura/métodos , Lectinas Tipo C/metabolismo , Linfangiogênese , Glicoproteínas de Membrana/metabolismo , Monócitos/metabolismo , Animais , Terapia Baseada em Transplante de Células e Tecidos , Células Cultivadas , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Nus , Transdução de Sinais , Pele/lesões , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
J Palliat Care ; 29(2): 91-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23923472

RESUMO

OBJECTIVE: We aimed to identify which structures and processes of care are key determinants of overall satisfaction with palliative care. METHODS: A nationwide, multicentre, cross-sectional questionnaire survey was conducted with 501 bereaved family members of terminal cancer patients (effective response rate: 20.9 percent). Structures and processes were evaluated using the Care Evaluation Scale (CES). RESULTS: In univariate analyses, all domains of the CES were significantly associated with overall satisfaction with care. In multivariate analyses, the domains of physical care by physician, physical care by nurse, environment, and coordination positively influenced overall satisfaction. After case-mix adjustment, physical care by nurse, age of patient, and lower education level of bereaved family member remained as significant determinants. CONCLUSION: Our finding that nursing is the most critical determinant of overall satisfaction within many structure and process domains has an important implication for clinical quality improvement and resource allocation.


Assuntos
Comportamento do Consumidor/estatística & dados numéricos , Família , Cuidados Paliativos/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Assistência Terminal/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , República da Coreia , Inquéritos e Questionários
14.
Psychooncology ; 22(12): 2771-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23839783

RESUMO

OBJECTS: We aimed to assess whether awareness of a terminal illness can affect care decision making processes and the achievement of a good death in advanced cancer patients receiving palliative care services. METHODS: Awareness of terminal illness at the time of palliative care service admission was assessed by the health care professionals during the routine initial comprehensive assessment process and was recorded in the national terminal cancer patient registry. A follow-up nationwide bereavement survey was conducted, which contained questions regarding decision making processes and the Korean version of the Good Death Inventory. RESULTS: Among the 345 patients included in the final analysis, the majority (68.4%) of the patients were aware of the terminal illness. Awareness of the terminal illness tended to reduce discordances in care decision making (adjusted odds ratio = 0.55; 95% CI: 0.29-1.07), and increased the patients' own decision making when there were discordances between patients and their families (adjusted odds ratio = 3.79; 95% CI: 1.31-10.94). The Good Death Inventory score was significantly higher among patients who were aware of their terminal illnesses compared with those who were not (5.04 vs. 4.80; p = 0.013) and especially in the domains of 'control over the future' (5.18 vs. 4.04; p < 0.001), 'maintaining hope and pleasure' (4.55 vs. 3.92; p = 0.002), and 'unawareness of death' (4.41 vs. 4.26; p = 0.024). CONCLUSION: Awareness of the terminal illness had beneficial effect on the harmonious decision making, patient autonomy, and patient's quality of death. Disclosure of terminal illness should be encouraged.


Assuntos
Atitude Frente a Morte , Conscientização , Luto , Tomada de Decisões , Família , Neoplasias , Cuidados Paliativos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Estudos Prospectivos , Assistência Terminal , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-23695570

RESUMO

YhgD is a member of the TetR-family transcription factors, which regulate genes encoding proteins involved in multidrug resistance, virulence, osmotic stress and pathogenicity. YhgD from the alkaliphilic bacterium Bacillus halodurans was cloned and overexpressed in Escherichia coli. YhgD (Bh2145) from B. halodurans is composed of 193 amino-acid residues with a molecular mass of 21 853 Da. YhgD was crystallized at 296 K using ethylene glycol as a precipitant by the sitting-drop vapour-diffusion method. The crystal diffracted to 1.9 Šresolution and belonged to the apparent triclinic space group P1, with unit-cell parameters a = 37.22, b = 47.85, c = 54.15 Å, α = 92.75, ß = 107.9, γ = 90.27°. The asymmetric unit is likely to contain two molecules of monomeric YhgD, giving a crystal volume per mass (VM) of 2.05 Å(3) Da(-1) and a solvent content of 40.2%.


Assuntos
Bacillus , Proteínas de Bactérias/química , Proteínas Repressoras/química , Cristalização , Difração de Raios X
16.
Support Care Cancer ; 21(10): 2707-17, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23708823

RESUMO

PURPOSE: Competency-based assessment helps to improve performance and to standardize education programs for hospice and palliative care professionals. This paper aims to report the process and results of developing the hospice and palliative care competencies by multidisciplinary experts in Korea. METHODS: The competency development task force team of Korean hospice and palliative care professionals was comprised of seven physicians, four nurses, two social workers, and two clergy. To build consensus regarding competencies, the team performed a two-round Delphi survey. The importance of competency domains was assessed by using a 5-point Likert scale. After the completion of the Delphi survey, final competency domains were decided in a consensus meeting. RESULTS: The competencies were composed of knowledge, skills, and attitudes. The competency domains were identified as the following: 11 domains and 16 subdomains for physicians, 11 domains for nurses, 5 domains and 15 subdomains for social workers, as well as 3 domains and 5 subdomains for spiritual care providers. The high importance domains were different by specialties. Physical care and treatment for physicians, symptom management for nurses, bereavement care for social workers, and communication for spiritual care providers were ranked as highly important. For nurses and spiritual care providers, attitude-related domains were ranked the highest in importance. CONCLUSION: The competencies developed by multidisciplinary professionals are useful to identify the appropriate roles of each hospice and palliative care specialist involved in a team approach to patient care.


Assuntos
Educação Baseada em Competências/métodos , Técnica Delphi , Cuidados Paliativos na Terminalidade da Vida/normas , Neoplasias/terapia , Cuidados Paliativos/normas , Educação Baseada em Competências/normas , Educação de Pós-Graduação em Medicina , Educação de Pós-Graduação em Enfermagem , Hospitais para Doentes Terminais , Humanos , Enfermeiras e Enfermeiros , Médicos , República da Coreia , Serviço Social/educação
17.
Biomaterials ; 34(8): 1929-41, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23267826

RESUMO

Ex vivo expansion of human circulating angiogenic cells is a major challenge in autologous cell therapy for ischemic diseases. Here, we demonstrate that hematosphere-derived CXCR4(+)CD31(+) myeloid cells using peripheral blood possess robust proangiogenic capacity such as formation of vessel-like structures and tip cell-like morphology in Matrigel. We also found that CD31 positive myeloid cells are principal cellular component of hematospheres by magnetic cell sorting. Flow cytometry analysis showed that fresh peripheral blood contained 40.3 ± 15.2% of CXCR4(+)CD31(+) myeloid cells, but at day 5 of hematosphere culture, most of myeloid cells were CXCR4(+)CD31(+) by 86.9 ± 5.4%. Hematosphere culture significantly increased the production of angiogenic niche-supporting cytokines. Moreover, CD31-homophilic interaction and VEGF-VEGF receptor loop signaling were essential for sphere formation and acquisition of angiogenic capacity in hematospheres. Matrigel plug and ischemic hindlimb model provide in vivo evidence that hematosphere-derived myeloid cells have highly vasculogenic capacities, participate in new and mature vessel formation, and exert therapeutic effects on ischemic hindlimb. In conclusion, our strategy for ex vivo expansion of human CXCR4(+)CD31(+) angiogenic cells using hematospheres provides an autologous therapeutic cell source for ischemic diseases and a new model for investigating the microenvironment of angiogenesis.


Assuntos
Técnicas de Cultura de Células/métodos , Monócitos/citologia , Monócitos/metabolismo , Neovascularização Fisiológica , Receptores CXCR4/metabolismo , Adulto , Animais , Células Cultivadas , Microambiente Celular/efeitos dos fármacos , Colágeno/farmacologia , Combinação de Medicamentos , Membro Posterior/irrigação sanguínea , Membro Posterior/patologia , Humanos , Isquemia/patologia , Isquemia/terapia , Laminina/farmacologia , Receptores de Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Nus , Monócitos/efeitos dos fármacos , Monócitos/transplante , Neovascularização Fisiológica/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Proteoglicanas/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Psychooncology ; 22(3): 564-71, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22275212

RESUMO

BACKGROUND: We examined factors associated with positive consequences for family members who served as caregivers of terminal cancer patients. METHODS: We conducted a nationwide cross-sectional survey of 501 bereaved family members who served as caregivers for terminal cancer patients. The main outcomes were measured by the previously developed Caregiving Consequences Inventory, which assesses perceived rewards and burdens of caregiving. RESULTS: Bereaved family caregivers reported high levels of perceived rewards and burden. Among the characteristics of bereaved family members, older age, female gender, and having a religion were associated with some domains of perceived rewards, but being a spouse of a patient was negatively associated with some domains of perceived rewards. Caregiver depression or perceived burden did not affect positive consequences of caregiving. However, receiving bereavement care was significantly associated with positive outcome in all four perceived reward domains (sense of mastery [adjusted odds ratio {aOR} = 1.69; 95% CI, 1.05-2.70]; appreciation for others [aOR = 2.19; 95% CI, 1.27-3.76]; meaning in life [aOR = 1.80; 95% CI, 1.13-2.89]; and reprioritization about his/her life [aOR = 2.02; 95% CI, 1.27-3.19]). CONCLUSIONS: Family caregivers of terminal cancer patients experience burdens, but caregiving also has positive consequences. This study has important implications for the development of bereavement interventions that aim to encourage positive outcomes and reduce negative outcomes for caregivers.


Assuntos
Cuidadores/psicologia , Cuidados Paliativos na Terminalidade da Vida/psicologia , Neoplasias/enfermagem , Assistência Terminal/psicologia , Adulto , Idoso , Efeitos Psicossociais da Doença , Estudos Transversais , Depressão/psicologia , Família/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , República da Coreia , Recompensa , Cônjuges/psicologia , Inquéritos e Questionários
19.
Pediatr Dent ; 34(5): 392-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23211915

RESUMO

PURPOSE: The goal of this study was to examine childhood overweight/obesity as a risk factor for adverse events during sedation for dental procedures. METHODS: This was a cross-sectional, retrospective, IRB-approved study that included 17 years of data (1992-2009). The outcome variables were desaturation, nausea/vomiting, prolonged sedation, and true apnea. The major explanatory variables were weight percentiles and BMI percentiles. RESULTS: A total of 510 patients met the inclusion criteria. Of these, 431 (86%) experienced no adverse events, 73 (14%) experienced one or more adverse events, and 6 had missing data. BMI data were available for a nested cohort of 103 children. Patients who experienced one or more adverse events had higher mean weights and BMI percentiles, though differences were not statistically significant. Another way to conceptualize the BMI data is to consider that 12% of the normal weight children experienced one or more adverse events versus 18% of the overweight/obese. CONCLUSIONS: Overall, weight percentiles were higher in children who had one or more adverse events. Similarly, patients with higher BMI percentiles were more likely to experience adverse events. Although preliminary in nature, these findings suggest that childhood overweight/obesity may be associated with adverse events during sedation for dental procedures.


Assuntos
Anestesia Dentária/efeitos adversos , Hidrato de Cloral/efeitos adversos , Sedação Consciente/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Sobrepeso/complicações , Período de Recuperação da Anestesia , Anestesia Dentária/métodos , Apneia/etiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hipóxia/etiologia , Masculino , Oxiemoglobinas/análise , Segurança do Paciente , Náusea e Vômito Pós-Operatórios/etiologia , Estudos Retrospectivos
20.
Int Neurourol J ; 16(3): 132-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23094219

RESUMO

PURPOSE: We aimed primarily to investigate the level of health-related quality of life (HRQoL), lower urinary tract symptoms (LUTS), and depression in older adults and secondly to identify the impact of LUTS and depression on HRQoL. METHODS: A community-based cross-sectional study was conducted from April to November 2010. Participants were recruited from five community senior centers serving community dwelling older adults in Jeju city. Data analysis was based on 171 respondents. A structured questionnaire was used to guide interviews; the data were collected including demographic characteristics, body mass index, adherence to regular exercise, comorbidities (hypertension, diabetes mellitus, and osteoarthritis), depression, urinary incontinence, LUTS (measured via the International Prostate Symptom Score [IPSS]), and HRQoL as assessed by use of the EQ-5D Index. Stepwise multiple regression analysis was used to test predictors of HRQoL. RESULTS: Eighteen percent (18.6%) of the respondents reported depressive symptoms. The mean LUTS score was 8.9 (IPSS range, 0 to 35). The severity of LUTS, was reported to be mild (score, 0 to 7) by 53% of the respondents, moderate (score, 8 to 19) by 34.5%, and severe (score, 20 to 35) by 12.5%. HRQoL was significantly predicted by depression (Partial R(2)=0.193, P<0.01) and LUTS (Partial R(2)=0.048, P=0.0047), and 24% of the variance in HRQoL was explained. CONCLUSIONS: LUTS and depression were the principal predictors of HRQoL in older adults.

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