RESUMO
OBJECTIVE: The aim of this review was to explore the experiences of nursing students participating in end-of-life education programs. DESIGN: A systematic review. DATA SOURCES: Exhaustive literature searches were performed using seven electronic databases: Medline, Scopus, Web of Science, CINAHL Plus, Dialnet Plus, Eric and Cuiden Plus. REVIEW METHODS: In total, 6572 studies published from 2008 until 2018 were examined. The Critical Appraisal Skills Program was used to assess the quality of the studies included in the review. The findings were synthesized using meta-aggregation. RESULTS: Seventeen studies were included in this systematic review, representing a sample of 606 nursing students. Simulation methods were most common among the educational programs analyzed. The analysis of qualitative data allowed us to identify 260 illustrations which were grouped into 14 categories and three themes: feelings and emotions during the performance of the pedagogical activity, end-of-life education among nursing students and competencies acquired on death and end-of-life. The most highlighted communication skills were learning to listen and building confidence to speak with the patient, family and the general public. CONCLUSIONS: End-of-life programs generally helped students acquire communication skills, learn concepts and improve the administration of this type of care. In addition, they perceived the experience as an opportunity to learn more about oneself, gain trust and support critical thinking. Nonetheless, the evidence available in this field is limited due to the small number of studies, plus the limited data reported. Thus, further studies on this subject are necessary.
RESUMO
The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. Herein we show that the adenosine-to-inosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mouse models, whereas its overexpression has the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early-stage lung cancer, but harboring ADAR1 gene amplification, have poor outcomes. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis.
Assuntos
Adenosina Desaminase/genética , Amplificação de Genes , Neoplasias Pulmonares/etiologia , Edição de RNA , Proteínas de Ligação a RNA/genética , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Oncogenes , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
We have investigated the genotype and allelic distribution of germline restriction fragment length polymorphisms of the T-cell receptor beta chain, segment C beta, and two variable segments which are in linkage disequilibrium, V beta 8 and V beta 11, in 42 insulin-dependent diabetes mellitus (IDDM) patients and in 51 healthy blood donors used as controls. Recently, several works have reported contradictory results showing or not showing an association between polymorphic alleles of the C beta gene and diabetes type I. We found no significant differences in the allele, genotype, and haplotype distribution of the gene segments studied, between IDDM patients and control populations.
Assuntos
Diabetes Mellitus Tipo 1/genética , Receptores de Antígenos de Linfócitos T/genética , Adolescente , Alelos , Criança , Pré-Escolar , DNA/análise , Sondas de DNA , Eletroforese em Gel de Poliacrilamida , Genótipo , Haplótipos , Humanos , Lactente , Recém-Nascido , Polimorfismo de Fragmento de Restrição , Receptores de Antígenos de Linfócitos T alfa-betaRESUMO
CD1 molecules are specialized in presenting lipidic antigens to T lymphocytes. They are structurally and evolutionary related to MHC molecules and show very limited polymorphism. We have previously described and partially characterized a new human CD1A allele differing from the wild type CD1A by a substitution of Cysteine by Tryptophan at position 52 in the alpha1 domain of the CD1A molecule. The frequency of this allele varies from 10% in individuals of Caucasian origin to 56% in Chinese people. The aim of the present work was to structurally characterize this CD1A allele. To do this we have cloned and sequenced the full-length cDNA encoding the new CD1A allele. The cDNA sequence of this allele encodes a protein differing the wild type in two amino acids at positions 14 (Threonine versus Isoleucine) and 52 (Cysteine versus Tryptophan). The cDNAs encoding both wild type and mutant CD1A were cloned in the expression vector pSRalphaNeo and transfected into C1R and L721.221 cells. Cell surface expression of the protein products in transfected cell lines were analyzed by flow cytometry and immunoprecipitation using CD1a-specific monoclonal antibodies. Our results indicate that both allelic products are efficiently expressed on the cell surface.
Assuntos
Alelos , Antígenos CD1/química , Antígenos CD1/genética , Variação Genética/imunologia , Anticorpos Monoclonais/análise , Antígenos CD1/biossíntese , Antígenos CD1/imunologia , Linhagem Celular Transformada , Clonagem Molecular/métodos , DNA Complementar/isolamento & purificação , Citometria de Fluxo , Vetores Genéticos/biossíntese , Vetores Genéticos/imunologia , Humanos , Testes de Precipitina , Transfecção , Células Tumorais CultivadasRESUMO
DNA polymorphisms (RFLPs) of the human complement component C6, C7, and C9 genes were studied in three C7-deficient (C7D) families, one C6-deficient (C6D) family, and one C9-deficient (C9D) family. The 3 loci are closely linked on human chromosome 5. The haplotypes carrying the "silent" allele (C7*Q0, C6*Q0, and C9*Q0) were defined in each family, allowing for the detection of carriers among asymptomatic relatives. This paper describes familial studies on a type of hereditary trait, characterized by recurrent Neisseria infections in individuals homozygous for "silent" alleles at the C6, C7, or C9 loci.
Assuntos
Alelos , Complemento C6/deficiência , Complemento C6/genética , Complemento C7/deficiência , Complemento C7/genética , Complemento C9/deficiência , Complemento C9/genética , Feminino , Haplótipos , Heterozigoto , Humanos , Masculino , Infecções Meningocócicas/genética , Infecções Meningocócicas/imunologia , Linhagem , Polimorfismo de Fragmento de Restrição , Recidiva , Sepse/genética , Sepse/imunologiaRESUMO
Promoter CpG island hypermethylation of tumor suppressor genes is an epigenetic hallmark of human cancer commonly associated with nucleosome occupancy and the transcriptional silencing of the neighboring gene. Nucleosomes can determine the underlying DNA methylation status. Herein, we show that the opposite is also true: DNA methylation can determine nucleosome positioning. Using a cancer model and digital nucleosome positioning techniques, we demonstrate that the induction of DNA hypomethylation events by genetic (DNMT1/DNMT3B deficient cells) or drug (a DNA demethylating agent) approaches is associated with the eviction of nucleosomes from previously hypermethylated CpG islands of tumor suppressor genes. Most importantly, the establishment of a stable cell line that restores DNMT1/DNMT3B deficiency shows that nucleosomes reoccupy their positions in de novo methylated CpG islands. Finally, we extend these results to the genomic level, combining a DNA methylation microarray and the nucleosome positioning technique. Using this global approach, we observe the dependency of nucleosome occupancy upon the DNA methylation status. Thus, our results suggest that there is a close association between hypermethylated CpG islands and the presence of nucleosomes, such that each of these epigenetic mechanisms can determine the recruitment of the other.
Assuntos
Ilhas de CpG/genética , Metilação de DNA/genética , Nucleossomos/genética , Linhagem Celular Tumoral , Montagem e Desmontagem da Cromatina , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/deficiência , DNA (Citosina-5-)-Metiltransferases/genética , Genes Supressores de Tumor , Células HCT116 , Humanos , Nucleossomos/metabolismo , Regiões Promotoras Genéticas/genética , DNA Metiltransferase 3BAssuntos
Monócitos/efeitos dos fármacos , Muromonab-CD3/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Linhagem Celular , Células Cultivadas , Citotoxicidade Imunológica/efeitos dos fármacos , Citometria de Fluxo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Monócitos/imunologiaRESUMO
Spry2 has been characterized as a negative regulator of the extracellular-regulated kinase (ERK) pathway. In this study we analysed whether epigenetic alterations of hSpry2 promoter occur in human lymphoid/hematopoietic malignancies. Our results revealed that hSpry2 promoter was hypermethylated in the HT cell line derived from a B-cell diffuse lymphoma, which correlated with decreased hSpry2 expression. We detected deregulation of the ERK pathway in these cells, but not in other blood cell lines expressing hSpry2. In addition, the ectopic overexpression of hSpry2 in HT cells drastically reduced the activation of ERK upon phorbol 12-myristate-13-acetate stimulation. Nude mice inoculated with HT mock cells developed tumors seven times larger than those from HT-hSpry2-transfected cells. We found hypermethylation of hSpry2 promoter in 37% (26 cases out of 71) of primary tumors from patients with B-cell diffuse lymphoma but none in normal B lymphocytes from 37 healthy individuals. Finally, we detected that hSpry2 promoter hypermethylation was associated with a significant decrease in the 5-year survival rate. These data suggest that hSpry2 could be important in lymphoid malignancies.
Assuntos
Epigênese Genética , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Linfoma de Células B/genética , Inibidores de Proteínas Quinases/farmacologia , Animais , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Linfoma de Células B/enzimologia , Proteínas de Membrana , Camundongos , Camundongos Nus , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Methyl-cytosine-phosphate-guanine (CpG)-binding domain (MBD) proteins are bound to hypermethylated promoter CpG islands of tumor suppressor genes in human cancer cells, although a direct causal relationship at the genome-wide level between MBD presence and gene silencing remains to be demonstrated. To this end, we have inhibited the expression of MBD proteins in HeLa cells by short hairpin RNAs; and studied the functional consequences of MBD depletion using microarray-based expression analysis in conjunction with extensive bisulfite genomic sequencing and chromatin immunoprecipitation. The removal of MBDs results in a release of gene silencing associated with a loss of MBD occupancy in 5'-CpG islands without any change in the DNA methylation pattern. Our results unveil new targets for epigenetic inactivation mediated by MBDs in transformed cells, such as the cell adhesion protein gamma-parvin and the fibroblast growth factor 19, where we also demonstrate their bona fide tumor suppressor features. Our data support a fundamental role for MBD proteins in the direct maintenance of transcriptional repression of tumor suppressors and identify new candidate genes for epigenetic disruption in cancer cells.
Assuntos
Ilhas de CpG , Epigênese Genética , Inativação Gênica , Genes Supressores de Tumor , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Metilação de DNA , Fatores de Crescimento de Fibroblastos/metabolismo , Células HeLa , Humanos , Modelos Biológicos , Ligação Proteica , Estrutura Terciária de Proteína , Interferência de RNA , RNA Interferente Pequeno/metabolismoRESUMO
The genes encoding for six receptors involved in the proinflammatory response lie on different chromosomes. Two receptors for N-formylpeptides (FPR1, FPR2), one homologue of these (FPRL2), and the receptor for complement fragment C5a (C5aR) are encoded by four genes mapped to human chromosome 19. The genes encoding two receptors for Interleukin-8 (IL8RA, IL8RB) have been located on human chromosome 2. In this report we describe the physical linkage between these genes in two different clusters. DNA fragments obtained by digestion with several restriction enzymes were separated by pulsed field gel electrophoresis. Nylon filters were hybridized with probes corresponding to the complete translated sequences of these genes. These probes were obtained from a human neutrophil cDNA-library. The four genes on chromosome 19 are contained in a 200 kilobase (kb) fragment. Both Interleukin-8 receptors are on a 150 kb fragment. The complete translated sequences for these genes were amplified from genomic DNA, indicating that they are contained in a single exon.
Assuntos
Cromossomos Humanos , Receptores de Complemento/genética , Receptores Imunológicos/genética , Receptores de Interleucina/genética , Receptores de Peptídeos/genética , Sequência de Bases , Evolução Biológica , Mapeamento Cromossômico , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 2 , Formiatos , Ligação Genética , Genoma Humano , Humanos , Inflamação/genética , Íntrons/genética , Dados de Sequência Molecular , Família Multigênica , Receptor da Anafilatoxina C5a , Receptores de Formil Peptídeo , Receptores de Interleucina-8ARESUMO
To investigate the significance of gastric xanthelasma, a retrospective review of 109 cases with an endoscopic diagnosis of this lesion was undertaken. A predominance in older patients was noted, with a similar distribution in antrum and fornix. In 15 cases (16.6%) they were multiple. They were occasionally associated with gastric erosions. In particular they were associated with chronic gastritis and intestinal metaplasia (48.9%). It is therefore concluded that gastric xanthelasma is not a rare lesion and that it is frequently associated with senile degenerative changes in the gastric mucosa.
Assuntos
Gastroenteropatias/diagnóstico , Xantomatose/diagnóstico , Adulto , Fatores Etários , Idoso , Animais , Biópsia , Doença Crônica , Cães , Endoscopia , Gastrite/complicações , Gastroenteropatias/complicações , Gastroenteropatias/patologia , Gastroscopia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Estômago/patologia , Xantomatose/complicações , Xantomatose/patologiaRESUMO
The genes for human complement components C6, C7, and C9 are linked on chromosome 5. In this report we describe the physical linkage between C6 and C7 genes. DNA fragments obtained by digestion with several rare-cutting restriction enzymes were separated through pulsed field gel electrophoresis. Hybridization with probes corresponding to the 5' and 3' ends of the three cDNAs showed common bands for the C6 and C7 genes. Both genes are contained in a NotI fragment of 500 kilobases (kb). Moreover, the presence of common 3' C6 and 3' C7 fragments indicates that both genes are oriented in a tail-to-tail, reverse way relative to transcription. No evidence of physical linkage between C9 and C6 or C7 was found in the range 50 kb-2.5 megabases (Mb).
Assuntos
Mapeamento Cromossômico , Complemento C6/genética , Complemento C7/genética , Complemento C9/genética , Ligação Genética , HumanosRESUMO
With the aim of evaluating, in a controlled prospective fashion, the efficacy of monopolar electrocoagulation in the emergency treatment of bleeding gastric and stomal ulcers, 37 patients were studied: 16 were electrocoagulated (EC group) while the remaining 21 were treated by conventional methods (control group). The hemorrhage recurred in only one of the 16 patients belonging to the EC group, but in 11 of the 21 control patients (p less than 0.0005). Transfusion requirements were also reduced in the EC group (p less than 0.05), with no significant difference in relation to mortality. Stratifying the results according to hemorrhagic activity, electrocoagulation should be clearly effective in those patients with spurting hemorrhage, taking into account several limitations: deep ulcers bearing gross vessels, and lack of cooperation by the patient. Prophylactic treatment of the bleeding ulcer with a visible non-spurting vessel may be indicated whenever we make a proper selection of the patients with a greater possibility of hemorrhagic recurrence.
Assuntos
Eletrocoagulação/métodos , Úlcera Péptica Hemorrágica/cirurgia , Úlcera Gástrica/cirurgia , Adulto , Idoso , Ensaios Clínicos como Assunto , Gastroscopia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , RecidivaRESUMO
N-formyl peptides (FMLP) and complement fragment C5a are neutrophil chemoattractants. In humans, a single-copy gene was identified for the C5a receptor, and the receptor for FMLP (FPR1) is encoded by a single gene that shows 53% amino acid similarity to the C5aR. Two other human FPR1 homologues, FPR-like 1 (FPR2/FPRL1) and FPR-like 2 (FPRL2) have been cloned. The human C5aR, FPR1, FPRL1, and FPRL2 are physically linked. By direct sequencing or by sequencing plasmid clones we studied the C5aR and FPR genes from four non-human primates (chimpanzee, gorilla, orangutan, and macaque). The sequences showed 95% - 99% similarity to the human homologues, with the major divergences observed in macaque. In these genes, the transmembrane and the cytoplasmic domains are highly conserved, while the highest divergence corresponded to the extracellular loops involved in ligand binding. Additionally, we constructed a physical map of these genes in non-human primates. In all species the four genes were physically linked and we defined the relative orientation of the four genes in primates: C5aR>FPR1>FPR2 (FPRL1)>FPRL2.
Assuntos
Antígenos CD/genética , Evolução Molecular , Primatas/genética , Receptores de Complemento/genética , Receptores Imunológicos/genética , Receptores de Lipoxinas , Receptores de Peptídeos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Gorilla gorilla , Humanos , Macaca mulatta , Dados de Sequência Molecular , Pan troglodytes , Filogenia , Pongo pygmaeus , Primatas/classificação , Receptor da Anafilatoxina C5a , Receptores de Formil Peptídeo , Alinhamento de SequênciaRESUMO
Interleukin-8 is a chemokine with a potent neutrophil chemoattractant activity. In humans, two different cDNAs encoding human IL8 receptors designated IL8RA and IL8RB have been cloned. IL8RA binds IL8, while IL8RB binds IL8 as well as other alpha-chemokines. Both human IL8Rs are encoded by two genes physically linked on chromosome 2. The IL8RA and IL8RB genes have open reading frames (ORF) lacking introns. By direct sequencing of the polymerase chain reaction products, we sequenced the IL8R genes of cell lines from four non-human primates: chimpanzee, gorilla, orangutan, and macaca. The IL8RB encodes an ORF in the four non-human primates, showing 95% - 99% similarity to the human IL8RB sequence. The IL8RA homologue in gorilla and chimpanzee consisted of two ORF 98% - 99% identical to the human sequence. The macaca and orangutan IL8RA homologues are pseudogenes: a 2 base pair insertion generated a sequence with several stop codons. In addition, we describe the physical linkage of these genes in the four non-human primates and discuss the evolutionary implications of these findings.
Assuntos
Antígenos CD/genética , Receptores de Interleucina/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Ligação Genética , Gorilla gorilla/genética , Humanos , Macaca/genética , Dados de Sequência Molecular , Fases de Leitura Aberta , Pan troglodytes/genética , Reação em Cadeia da Polimerase , Pongo pygmaeus/genética , Receptores de Interleucina-8A , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido NucleicoRESUMO
We characterized the MHC-related 1 ( MR1) locus in two nonhuman primates species, Pongo pygmaeus and Pan troglodytes. MR1 cDNA sequences encoding several isoforms generated through alternative splicing were observed in both species. Amino acid alignment between the five species in which MR1 has been characterized to date - human, chimpanzee, orangutan, mouse, and rat - reveals a very high degree of conservation specially in the alpha1 and alpha2 domains of the molecule. The main differences concentrate in the transmembrane and cytoplasmic domains. In the three primates species there is a lysine residue inside the putative transmembrane domain which is not present in rodents. Furthermore, the MR1 cytoplasmic region is longer in rodents, with a conserved serine-containing motif that could be involved in endocytosis; remarkably, this motif is absent in the three primate species. We also describe the presence in the chimpanzee of a sequence homologous to the MR1P1 pseudogene previously found in humans.
Assuntos
Genes MHC Classe I/genética , Antígenos de Histocompatibilidade Classe I/genética , Pan troglodytes/genética , Pongo pygmaeus/genética , Sequência de Aminoácidos , Animais , Linhagem Celular Transformada , Clonagem Molecular , Sequência Conservada , Humanos , Antígenos de Histocompatibilidade Menor , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Homologia de Sequência de AminoácidosRESUMO
Human MR1 is a recently discovered, ubiquitously transcribed gene very similar to the HLA class I loci and of unknown function. Mouse and rat MR1 sequences have also been described showing high similarity with the human gene. The goal of this work was to investigate if human MR1 was polymorphic. We have found that DNA sequences of MR1-specific polymerase chain reaction (PCR) products obtained from samples of diverse ethnic origin were invariant except in one case in which two silent mutations were detected. We also found an MR1-like sequence displaying significant differences with the previously described, the most remarkable of which is a STOP codon in the alpha2 domain indicating that is a pseudogene.
Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Pseudogenes/imunologia , Sequência de Bases , Códon de Terminação/genética , Éxons , Humanos , Íntrons , Antígenos de Histocompatibilidade Menor , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , Pseudogenes/genéticaRESUMO
Short term sclerotherapy (by injection(s) around the bleeding point) is used for immediate control of massive haemorrhage from oesophagogastric varices. The usefulness of longterm sclerotherapy once short term sclerotherapy has been successfully carried out was assessed. Two treatment groups were studied: 50 patients were treated by 'combined' (short term followed by longterm) sclerotherapy; 56 patients were treated by short term sclerotherapy only. Patients included in the second group were treated by short term sclerotherapy only if a variceal rebleeding was present. The overall cumulative proportion of patients rebleeding was not significantly different in either group. Combined sclerotherapy patients, however, experienced less episodes of variceal haemorrhage and the source of haemorrhage was different (p < 0.002). Combined sclerotherapy was more efficient in preventing bleeding from oesophageal bleeding points but not those arising from a junctional source (p < 0.05). A greater incidence of oesophageal rebleeding was found in those patients whose first source of bleeding was oesophageal (p < 0.05). No significant difference was detected in survival expectancy between either group. In conclusion, after short term sclerotherapy is carried out successfully, those patients with bleeding from variceal bleeding points located on oesophageal mucosa should benefit most from a longterm sclerotherapy programme.