RESUMO
Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.
Assuntos
Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Plasticidade Celular/genética , Reprogramação Celular/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
The term vascular anomaly represents a broad spectrum of vascular pathology, including proliferating vascular tumours and vascular malformations. While the treatment of most vascular anomalies is multifactorial, interventional radiology procedures, including embolic therapy, sclerotherapy and laser coagulation among others, are playing an increasingly important role in vascular anomaly management. This review discusses the diagnosis and treatment of common vascular malformations, with emphasis on the technique, efficacy and complications of different interventional radiology procedures.
Assuntos
Radiografia Intervencionista/métodos , Malformações Vasculares/classificação , Malformações Vasculares/diagnóstico por imagem , Malformações Arteriovenosas/diagnóstico por imagem , Capilares/anormalidades , Hemangioma/diagnóstico por imagem , Humanos , Sistema Linfático/anormalidades , Mancha Vinho do Porto/diagnóstico por imagem , Neoplasias Vasculares/diagnóstico por imagem , Veias/anormalidadesRESUMO
Neutron depth profiling (NDP) is a mature, nondestructive technique used to characterize the concentration of certain light isotopes in a material as a function of depth by measuring the residual energy of charged particles in neutron induced reactions. Historically, NDP has been performed using a single detector, resulting in low intrinsic detection efficiency, and limiting the technique largely to high flux research reactors. In this work, we describe a new NDP instrument design with higher detection efficiency by way of spectrum summing across multiple detectors. Such a design is capable of acquiring a statistically significant charged particle spectrum at facilities limited in neutron flux and operation time.
Assuntos
Traumatismos do Braço/diagnóstico , Transtornos Traumáticos Cumulativos/diagnóstico , Doenças Profissionais/diagnóstico , Traumatismos do Braço/classificação , Traumatismos do Braço/etiologia , Transtornos Traumáticos Cumulativos/classificação , Transtornos Traumáticos Cumulativos/etiologia , HumanosRESUMO
We report treatment of a low grade parosteal osteosarcoma of the ring finger metacarpal in a patient who would not contemplate ray amputation because of her career. Surgery involved excision of the bone, extracorporeal radiation then re-implantation.
Assuntos
Neoplasias Ósseas/cirurgia , Metacarpo , Música , Doenças Profissionais/cirurgia , Osteossarcoma Justacortical/cirurgia , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Humanos , Metacarpo/cirurgia , Pessoa de Meia-Idade , Osteossarcoma Justacortical/diagnóstico por imagem , Reimplante , Tomografia Computadorizada por Raios XAssuntos
Comportamento de Escolha , Prestação Integrada de Cuidados de Saúde/organização & administração , Reforma dos Serviços de Saúde/organização & administração , Programas de Assistência Gerenciada/organização & administração , Controle de Custos , Alocação de Recursos para a Atenção à Saúde/organização & administração , Humanos , Marketing de Serviços de Saúde , Ontário , Estados UnidosRESUMO
BACKGROUND: Neonatal circumcision is a painful surgical procedure often performed without analgesia. We assessed the efficacy and safety of 5 percent lidocaine-prilocaine cream (Emla) in neonates undergoing circumcision. METHODS: We carried out a double-blind, randomized, controlled trial in 68 full-term male neonates: 38 were assigned to receive lidocaine-prilocaine cream, and 30 to receive placebo. One gram of lidocaine-prilocaine or placebo cream was applied to the penis under an occlusive dressing for 60 to 80 minutes before circumcision. Behavioral (facial activity and time spent crying) and physiologic (heart rate and blood pressure) responses were recorded during the procedure. Blood samples were obtained at various times after drug application for measurements of methemoglobin and plasma lidocaine, prilocaine, and o-toluidine (a metabolite of prilocaine). RESULTS: A total of 68 and 59 neonates were included in the safety and efficacy analyses, respectively. Demographic characteristics such as gestational age and birth weight did not differ between the lidocaine-prilocaine and placebo groups. During circumcision, the neonates in the lidocaine-prilocaine group had less facial activity (P= 0.01), spent less time crying (P<0.001), and had smaller increases in heart rate (P=0.007) than the neonates in the placebo group. Facial-activity scores were 12 to 49 percent lower during various steps of the procedure in the lidocaine-prilocaine group. As compared with neonates in the placebo group, infants in the lidocaine-prilocaine group cried less than half as much and had heart-rate increases of 10 beats per minute less. Blood methemoglobin concentrations (expressed as a percentage of the hemoglobin concentration) were similar (1.3 percent) in both groups. Lidocaine and prilocaine were detected in plasma in 23 (61 percent) and 21 (55 percent) of the infants treated with lidocaine-prilocaine cream, respectively. CONCLUSIONS: Lidocaine-prilocaine cream is efficacious and safe for the prevention of pain from circumcision in neonates.
Assuntos
Anestesia Local , Anestésicos Locais/uso terapêutico , Circuncisão Masculina/efeitos adversos , Lidocaína/uso terapêutico , Dor/prevenção & controle , Prilocaína/uso terapêutico , Anestesia Local/efeitos adversos , Anestésicos Locais/efeitos adversos , Choro , Método Duplo-Cego , Combinação de Medicamentos , Frequência Cardíaca , Humanos , Recém-Nascido , Lidocaína/efeitos adversos , Masculino , Metemoglobinemia , Pomadas , Dor/etiologia , Dor/fisiopatologia , Prilocaína/efeitos adversosRESUMO
During oogenesis in Drosophila, germ cells appear in sequential clusters of 16 interconnected cells. The events surrounding the differentiation of these cells are not fully understood. Here we present genetic and morphological analysis of mutations in the gene stand still (stil). Through complementation analyses we have refined the location of this gene to cyological region 49B-C. Our analyses of ovaries from ethylmethane sulfonate (EMS)-induced mutant alleles of this gene suggest that mutations in the stil gene produce a wide range of phenotypic abnormalities, from the absence of germ cells in the most severe alleles, to egg chambers with cytoskeletal defects in the less severe alleles. Our results suggest a role for this gene in specifying or maintaining a cytoskeletal component, with consequences during oogenesis and possibly during germ line sex determination.
Assuntos
Drosophila/genética , Genes de Insetos , Oogênese/genética , Ovário/citologia , Óvulo/citologia , Actinas/ultraestrutura , Alelos , Animais , Diferenciação Celular/genética , Mapeamento Cromossômico , Citoesqueleto/ultraestrutura , Feminino , Mutação , FenótipoRESUMO
With the increasing popularity of day case surgery it is important to ensure that safe and appropriate techniques are being used. We retrospectively reviewed a large series of 732 patients who underwent planned day case hand surgery under intravenous regional anaesthesia (modified Bier's block) over a 5-year period. We found a modified Bier's block to be ideally suited to day case surgery with no deaths, minimal morbidity and a success rate in excess of 98%.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Mãos/cirurgia , Bloqueio Nervoso , Adulto , Idoso , Anestesia Local/métodos , Anestésicos Locais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , PrilocaínaRESUMO
Haemangioma of bone is a rare benign tumour of blood vessels. We report a case arising in a middle phalanx and the problems encountered in its management.
Assuntos
Neoplasias Ósseas/cirurgia , Dedos/patologia , Hemangioma/cirurgia , Adulto , Neoplasias Ósseas/patologia , Feminino , Hemangioma/patologia , HumanosRESUMO
The female-sterile ovarian tumor gene, otu, is located in cytological region 7F1 on the Drosophila melanogaster chromosome map. We have mapped the gene at the molecular level by using four dysgenic alleles and two revertant derivatives of these alleles as well as an ethyl methanesulfonate-induced allele. The insertional (dysgenic) changes were all associated with one restriction fragment, and its size was restored after phenotypic reversion. One ethyl methanesulfonate-induced allele had a deletion in the restriction fragment adjacent (distal) to the fragment altered in the insertional alleles. These two restriction fragments were immediately adjacent to the s38 chorion gene. Associated with the two altered restriction fragments were two RNA species, an abundant 3.2-kilobase (kb) poly(A)+ RNA and a minor 4.0-kb RNA. Several other less-abundant RNA species were detectable with more-sensitive single-stranded RNA probes. The otu gene was transcribed proximal to distal relative to the centromere; this was opposite to the direction of transcription of the adjacent s38 gene. During development, the 3.2-kb RNA was absent in larvae, first appeared in the pupal stages, and persisted in adult females, in which it was most prevalent in the ovaries. The DNA that hybridized to the 3.2-kb ovarian RNA hybridized to four different RNAs found in the testes but not in the rest of the adult male. These testis-enriched RNAs were transcribed from the same strand of DNA as the ovarian transcripts.
Assuntos
Drosophila melanogaster/genética , Genes , Transcrição Gênica , Alelos , Animais , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Heterozigoto , Infertilidade Feminina , Mutação , Hibridização de Ácido Nucleico , Neoplasias Ovarianas , Polimorfismo GenéticoRESUMO
Breakdancing is an acrobatic dance that involves spinning on various parts of the body including the head, dorsal spine and hand. Three cases are reported of partial rupture of the ulnar collateral ligament (UCL) of the thumb, associated with a fracture of the base of the proximal phalanx which occurred as a result of torsional forces applied to the abducted and hyperextended thumb. It appears to be a distinct clinical entity. In all cases, open reduction was required and led to excellent functional recovery.
Assuntos
Dança , Fraturas Fechadas/etiologia , Ligamentos Articulares/lesões , Polegar/lesões , Adolescente , HumanosRESUMO
DNA replication patterns in the nurse and follicle cells of wild type and a female sterile mutant, fs(1)1304, of Drosophila melanogaster have been studied by DNA-Feulgen cytophotometry, using a cell dispersal technique that allowed the measurement of DNA amounts in individual nuclei from egg chambers of known developmental stages. DNA-Feulgen values associated with various ovarian nuclei from egg chambers at different stages of development were used to assess a base line DNA content for ovarian tissues and to estimate the extent of DNA replication in the nurse cells and follicle cells of growing and mature egg chambers. Our data show that both the nurse and follicle cells undergo multiple cycles of endonuclear DNA replication and that there may be selective amplification as well as underreplication by portions of the genome in these highly polyploid, ovarian cells. Alternative models are proposed to account for the DNA replication patterns observed. Comparisons of DNA-Feulgen levels in wild type ovarian nuclei with those found for the fs(1)1304 mutant and its heterozygote in the balanced stock fs/FM3, show that equivalent DNA levels are present in follicle cell nuclei from all three types of females. Nurse cell nuclei in the homozygous fs stock, however, fail to achieve the same high DNA levels observed in both fs/FM3 and wild type nurse cell nuclei. Although the nuclei of follicle cells in ovaries from fs/fs females appear morphologically like those surrounding egg chambers in wild type ovaries, nurse cell nuclei from mutant females show a more compacted organization of their chromatin than found for nurse cell nuclei from wild type ovaries at similar developmental stages. Our findings suggest that a major effect of the fs(1)1304 mutation may be on the coiling behavior of chromatin and the conformation of DNA-protein moieties in both nurse cell and follicle cell nuclei. These changes in chromatin structure apparently are manifest by perturbations in DNA replication patterns and normal gene function in these biosynthetically active cells.
Assuntos
Corantes , DNA/análise , Drosophila melanogaster/análise , Corantes de Rosanilina , Animais , Núcleo Celular/análise , Drosophila melanogaster/genética , Feminino , Gônadas/análise , Mutação , Coloração e RotulagemRESUMO
A mouse genomic library in lambda Charon 4A was screened for putative ribosomal protein genes using a fragment of the gene encoding Drosophila ribosomal protein 49 as a hybridization probe under nonstringent hybridization conditions. A recombinant phage was selected and its restriction enzyme map determined. The major species of mouse poly(A)+ mRNA homologous to the putative gene is about 740 nucleotides long.
Assuntos
Drosophila melanogaster/genética , Proteínas Ribossômicas/genética , Animais , Evolução Biológica , Mapeamento Cromossômico , Enzimas de Restrição do DNA , Genes , Camundongos , Hibridização de Ácido Nucleico , Poli A/genética , RNA Mensageiro/genéticaAssuntos
Consumo de Bebidas Alcoólicas , Psicologia Criminal , Adulto , Humanos , Masculino , Prisioneiros , Escócia , AutorrevelaçãoRESUMO
The female sterile mutant of Drosophila melanogaster, fs(1)1304 (1-19 +/- 2), has been characterized. Our studies show that the mutation affects the organization of nucleolar material in the ovarian nurse cells and the pattern of RNA metabolism in the ovary. Autoradiographic analysis of incorporation of 3H-uridine in vivo and analysis of 3H-uridine incorporation into high molecular weight RNA in vitro suggest that RNA from the ovaries of homozygous fs flies is degraded at a higher rate than that from heterozygous fs and wild-type ovaries. It is likely that the RNA class affected is ribosomal RNA. These data are discussed in the context of the functional role for the wild-type gene allelic to fs(1)1304, and it is suggested that one of the effects of the mutation may be on the biogenesis of ribosomes that are to be stored in the oocyte.
Assuntos
Drosophila melanogaster/metabolismo , RNA/metabolismo , Animais , Drosophila melanogaster/genética , Feminino , Genes , Cinética , Mutação , Ovário/metabolismo , RNA/análise , ReproduçãoRESUMO
A technique is described for treating severe compound injuries of the phalanges either single or multiple, with transverse Kirschner wires bonded with acrylic cement. The operative procedure, post-operative management and advantages of the technique are described.