RESUMEN
The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimer's disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted whole-genome exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N=13), I-II (N=20), III-IV (N=19) and V-VI (N=19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N=30), and in patients with late-onset AD (N=37), dementia with Lewy bodies (N=17) and Parkinson disease (N=36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Protein-protein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.
Asunto(s)
Enfermedad de Alzheimer/genética , Ovillos Neurofibrilares/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Enfermedad de Alzheimer/patología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Encéfalo/patología , Moléculas de Adhesión Celular Neuronal/genética , Ciclooxigenasa 2/genética , Progresión de la Enfermedad , Proteínas de la Matriz Extracelular/genética , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Genes/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Proteínas de la Membrana , Miosina Tipo V/genética , Proteínas del Tejido Nervioso/genética , Ovillos Neurofibrilares/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína Reelina , Serina Endopeptidasas/genéticaRESUMEN
OBJECTIVES: The fused in sarcoma (FUS) protein is a 526 amino acid and its expression is ubiquitous. Recently, mutations in a gene coding FUS have been identified in familial amyotrophic lateral sclerosis (ALS). Also, FUS has been found in neuronal cytoplasmic inclusions in sporadic forms of ALS, suggesting that FUS has an important role in the neurodegeneration occurring in sporadic disease. However, there has been no study of FUS in ALS skin. MATERIAL AND METHODS: We made a quantitative immunohistochemical study of the expression of FUS in the skin from patients with sporadic ALS and controls. RESULTS: The proportion of FUS-immunoreactive (ir) cells in the epidermis in ALS patients was significantly higher (P < 0.001) than in controls. There was a significant positive relationship (r = 0.78, P < 0.001) between the proportion and duration of illness in ALS patients. The optical density of FUS-ir cells in the epidermis in ALS patients is markedly stronger (P < 0.001) than in controls. There was a significant positive relation (r = 0.49, P < 0.05) between the immunoreactivity and duration of illness in ALS patients. CONCLUSIONS: These data suggest that changes of FUS in ALS skin are related to the disease process, and that metabolic alterations of FUS may take place in the skin of patients with ALS.
Asunto(s)
Esclerosis Amiotrófica Lateral/patología , Proteína FUS de Unión a ARN/metabolismo , Piel/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína FUS de Unión a ARN/genéticaRESUMEN
Flaps composed of the latissimus dorsi and the serratus anterior muscles have been used to repair extensive defects in 10 patients with no remarkable disabilities of shoulder function. The latissimus dorsi and serratus anterior muscles are consistently nourished through the subscapular-thoracodorsal vessels. Thus, the 2 flaps can be based on 1 vascular pedicle. If required, the ribs beneath the serratus anterior muscle, which are vascularized by the periosteal circulation, can be transferred with the muscle. The vascular pedicle of this flap is long and anatomically reliable. Care must be taken to avoid tension or torsion of the pedicle when positioning the flap.
Asunto(s)
Colgajos Quirúrgicos , Adulto , Anciano , Dorso/cirugía , Procedimientos Quirúrgicos Dermatologicos , Femenino , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Úlcera de la Pierna/cirugía , Masculino , Persona de Mediana Edad , Músculos/cirugía , Músculos/trasplante , Costillas/cirugía , Trasplante de Piel , Infección de la Herida Quirúrgica/cirugíaAsunto(s)
Deformidades Adquiridas del Pie/cirugía , Pie/cirugía , Cirugía Plástica/métodos , Colgajos Quirúrgicos , Adulto , Niño , Femenino , Humanos , MasculinoRESUMEN
We have used 9 free latissimus dorsi myocutaneous flaps. All but 1 survived completely. This one showed superficial necrosis at the flap margin. Our operative techniques and experiences are reported here, with some of our results. A relatively large flap can be nourished by only one vascular pedicle, the subcapsular-thoracodorsal vessels. Though three are many vascular variations in the axillary region, the subscapular-thoracodorsal vessels are easily identifiable in our experience, and their diameters are always large enough for microvascular anastomosis. The bulk of this flap is one of its important features. Care must be taken in the design of the flap so that it fits exactly, and it should also be remembered that the volume of the flap will decrease greatly later on. The flap is remarkably simple, safe, and reliable. We believe it will be the method of choice in many microsurgical cases.
