RESUMEN
Immunoglobulin (Ig) domains are the most prevalent protein domain structure and share a highly conserved folding pattern; however, this structural family of proteins is also the most diverse in terms of biological roles and tissue expression. Ig domains vary significantly in amino acid sequence but share a highly conserved tryptophan in the hydrophobic core of this beta-stranded protein. Palladin is an actin binding and bundling protein that has five Ig domains and plays an important role in normal cell adhesion and motility. Mutation of the core tryptophan in one Ig domain of palladin has been identified in a pancreatic cancer cell line, suggesting a crucial role for this sole tryptophan in palladin Ig domain structure, stability, and function. We found that actin binding and bundling was not completely abolished with removal of this tryptophan despite a partially unfolded structure and significantly reduced stability of the mutant Ig domain as shown by circular dichroism investigations. In addition, this mutant palladin domain displays a tryptophan-like fluorescence attributed to an anomalous tyrosine emission at 341 nm. Our results indicate that this emission originates from a tyrosinate that may be formed in the excited ground state by proton transfer to a nearby aspartic acid residue. Furthermore, this study emphasizes the importance of tryptophan in protein structural stability and illustrates how tyrosinate emission contributions may be overlooked during the interpretation of the fluorescence properties of proteins.
Asunto(s)
Inmunoglobulina G/química , Inmunoglobulina G/genética , Mutación Missense , Sustitución de Aminoácidos , Animales , Dicroismo Circular , Dominios de Inmunoglobulinas , Ratones , Triptófano/química , Triptófano/genéticaRESUMEN
OBJECTIVES: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories. METHODS: We performed a case-control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome. RESULTS: The strongest finding (p = 2.01 × 10-6, odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance (p = 2.78 × 10-6). CONCLUSION: The identification of FZD1, as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development.
Asunto(s)
Estudio de Asociación del Genoma Completo , Esquizofrenia , Australia , Estudios de Cohortes , Receptores Frizzled/genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genéticaRESUMEN
BACKGROUND: Sternal wound infection and sternal dehiscence are very serious, sometimes life-threatening complications of cardiac surgery, which require immediate attention. The mortality rate can reach 50%. During the past 30 years,various flaps for coverage of sternal wounds have been described. OBJECTIVE: The authors objective was to evaluate their 7-year experience with flaps used for coverage of poststernotomy wounds, with an emphasis on flap selection and post repair complications. RESULTS: The records of 15 patients were reviewed. The most common coverage techniques were pectoralis major flap (n=5)and rectus abdominis flap (n=4). Four patients had both of these flaps. One patient had a latissimus dorsi flap, and another one had an omental flap. Eight of the 15 patients experienced a local complication; these included seroma(n=2), hematoma (n = 1), infection requiring debridement and antibiotics (n = 2), partial flap necrosis (n = 2) and abdominal hernia (n=1). The perioperative mortality rate was 13.3% (n = 2), and all deaths were attributable to multiple organ deficiency due to sepsis. CONCLUSIONS: Early debridement and coverage of the remained defects with flaps are the two main principles in the management of poststernotomy infected wounds, especially insituations where rapid wound healing and recovery are extremely important. Individual approach to each patient and proper selection of the method of reconstruction significantly reduces the postoperative morbidity and mortality rate.
Asunto(s)
Desbridamiento , Esternotomía , Colgajos Quirúrgicos , Dehiscencia de la Herida Operatoria/cirugía , Infección de la Herida Quirúrgica/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Desbridamiento/métodos , Femenino , Hematoma/etiología , Humanos , Masculino , Persona de Mediana Edad , Epiplón , Músculos Pectorales , Procedimientos de Cirugía Plástica , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Seroma/etiología , Esternotomía/efectos adversos , Músculos Superficiales de la Espalda , Dehiscencia de la Herida Operatoria/mortalidad , Infección de la Herida Quirúrgica/mortalidad , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
UNLABELLED: Reconstruction of complex mucocutaneous defects after ablative surgery for advanced cancer of the oropharynx, hypopharynx and larynx (Stages III and IV of disease according to TNM classification) with previous radiotherapy is a challenging problem for the plastic surgeon. The gastroomental free flap provides in these cases both a reliable mucosal lining of the digestive tract and soft tissue coverage in the neck. One-stage surgical excision and reconstruction improves the quality of life by reducing the hospitalization and providing recovery of the swallowing function. BACKGROUND: The method of reconstruction of the complex mucocutaneous defects that usually occur after extensive ablative surgery associated with radiotherapy for advanced malignant lesions of the oropharynx, hypopharynx and larynx should provide both digestive tract reconstruction and soft tissue coverage of the neck. The purpose of the article is to report our experience with the use of the gastroomental free flap for the reconstruction of such complex defects of the oro-and hypopharynx. METHOD: Gastro-omental free flap was used for one-stage reconstruction of complex defects of the oropharynx in four cases and hypopharynx in eleven cases between December 1990 and December 2008 after extensive ablative surgery for cancer. All fifteen patients had received previous irradiation. In all cases the tumor ablation was associated with neck dissection. RESULTS: There was one flap failure in this series (6.67%). Complications included: two cases of gastric outlet obstructions, one case of mild superficial bleeding of the transplanted gastric mucosa and three fistulas formed. Thirteen patients had adequate swallowing function after reconstruction of the digestive tract. CONCLUSION: Gastro-omental free flap represents a reliable and valuable solution in covering of extended and complex defects in the oral and cervical area following advanced cancer ablation.
Asunto(s)
Carcinoma de Células Escamosas/cirugía , Colgajos Tisulares Libres , Neoplasias Laríngeas/cirugía , Epiplón/trasplante , Procedimientos de Cirugía Plástica/métodos , Neoplasias Tonsilares/cirugía , Adulto , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Femenino , Humanos , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/radioterapia , Masculino , Persona de Mediana Edad , Disección del Cuello , Estadificación de Neoplasias , Calidad de Vida , Neoplasias Tonsilares/patología , Neoplasias Tonsilares/radioterapia , Resultado del TratamientoRESUMEN
Eukaryotes possess a mechanism that generates small interfering RNA (siRNA) and microRNA (miRNA) and use these to regulate gene expression at the transcriptional or post-transcriptional level. These small RNAs (21-24nt) are processed from long double-stranded RNA precursors by type III RNase enzymes, referred to as DICER or DICER-LIKE proteins (DCLs). In Arabidopsis, there are four DCL genes and their role in small RNA biogenesis and silencing has been the subject of intense study. DCL2 is less well studied than the other DCL proteins although it is known to play a role in formation of natural antisense siRNA and may be involved in transitive silencing of transgene transcripts. This study provides basic genomic information on DCL2 in the Nicotiana tabacum (NtDCL2) gene family and its probable roles in plant growth and development.
Asunto(s)
Proteínas de Arabidopsis/genética , Proteínas de Ciclo Celular/genética , Genes de Plantas , Nicotiana/genética , Ribonucleasa III/genética , Agrobacterium tumefaciens/genética , Agrobacterium tumefaciens/metabolismo , Arabidopsis/enzimología , Arabidopsis/genética , Bacteriófago lambda/genética , Bacteriófago lambda/metabolismo , Northern Blotting , Clonación Molecular , Silenciador del Gen , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Familia de Multigenes , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , ARN Mensajero/análisis , ARN Mensajero/genética , ARN de Planta/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ribonucleasas/genética , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Nicotiana/enzimología , Nicotiana/crecimiento & desarrolloRESUMEN
INTRODUCTION: Thyroid follicular adenomas (FA) and adenomatous thyroid nodules (AN) - lesions that are frequently found in areas with iodine deficiency, can be normo-/hypofunctioning (scintigraphically cold - SCN) or hyperfunctioning (scintigraphically hot - SHN) nodules. AIM: Evaluation of proliferation potential in thyroid nodules on tissue samples obtained at surgery from euthyroid patients clinically diagnosed with SCN and from patients with thyroid hyperfunction and SHN. MATERIALS AND METHODS: We investigated the proliferation activity estimated by assessing PCNA and Ki-67 proliferation markers in 20 SCN (eight FA and 12 AN) and 16 toxic nodules (six hyperfunctioning FA and 10 toxic multinodular goiters), on formalin-fixed and paraffin-embedded tissue samples, 4-5 µm thick; we used the immunohistochemical technique in LSAB system (DAB visualization) with anti-PCNA (PC10) and anti-Ki-67 (MIB-1) monoclonal antibodies. For each case, we calculated the proliferation index PI-PCNA and PI-Ki-67. The dates were statistically evaluated using the t-unpaired test. RESULTS: We observed a higher PI-PCNA in thyroid nodules than in the normal surrounding thyroid tissue, with statistically significant values for FA (14.3% vs. 3.8%; p<0.029) and also for AN (8.36% vs. 1.24%; p<0.001). The mean PI-Ki-67 in nodules vs. surrounding thyroid tissue was 1.64% vs. 1.10% in FA (p<0.35) and 1.07% vs. 0.51% in AN (p>0.05). We also noted: (1) significantly higher PI-PCNA values (p < 0.01) in FA (14.03%) than in AN (8.36%), as compared to statistically insignificant values for Ki-67 (1.64% vs. 1.07%; p>0.05); (2) increased proliferation rate (p<0.01) in thyroid nodules with aspects of lymphocytic thyroiditis (LT) (PI-Ki-67 was 1.21%) as compared to nodules without LT (PI-Ki-67 was 0.12%); (3) a mean PI-PCNA of 8.5% and PI-Ki-67 of 4.61% in toxic thyroid nodules (TTN) vs. 3.01% and 1.5% in normal surrounding thyroid, respectively. CONCLUSIONS: The clinical expression of SCN is the consequence of increased thyrocyte proliferation in the nodules; the increased proliferative potential of TTN thyrocytes is a common feature of nodules, independent of their histopathological characteristics.
Asunto(s)
Glándula Tiroides/patología , Glándula Tiroides/fisiopatología , Nódulo Tiroideo/patología , Nódulo Tiroideo/fisiopatología , Adenoma/patología , Proliferación Celular , Humanos , Antígeno Ki-67/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Glándula Tiroides/metabolismo , Nódulo Tiroideo/metabolismo , Tiroiditis/metabolismo , Tiroiditis/patologíaRESUMEN
Despite improvements in reconstructive techniques for pressure sores, recurrences are still seen frequently, and success rate remains variable. During 2003 - 2007, at the Emergency Hospital for Plastic Surgery and Burns in Bucharest, 27 patients underwent surgical repair of 45 pressure sores located at sacral (22 ulcers), ischial (12 ulcers) and trochanteric (11 ulcers) regions. The mean patient age was 57, 1 years (range 26 to 82 years). Mean postoperative follow-up was 6 months (range 2 months - 2 years). There were 18 complications for the 45 sores (40%). At 6 months postoperatively, recurrence was noted in 12 ulcers (27%). Details regarding indications, contraindications, advantages and disadvantages for different coverage options are outlined. The authors advocate the importance of surgical coverage in reducing morbidity, mortality and treatment costs.
Asunto(s)
Úlcera por Presión/cirugía , Colgajos Quirúrgicos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fémur/cirugía , Humanos , Isquion/cirugía , Masculino , Persona de Mediana Edad , Úlcera por Presión/patología , Recurrencia , Reoperación , Estudios Retrospectivos , Región Sacrococcígea/cirugía , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
AIMS: This study evaluates the behaviour in spiked sludge of a pathogenic bacteria, Listeria monocytogenes, by cultural and molecular techniques, and compares its survival with the one of a faecal indicator, Enterococcus faecium. METHODS AND RESULTS: Listeria monocytogenes strain Scott A and E. faecium(T) were followed for 17 days after inoculation in sludge. Kinetics of survival depended on the bacteria and on the technique used [most probable number method, direct plate count or real-time quantitative PCR (qPCR)]. The concentration of L. monocytogenes decreased rapidly regardless of the technique, but the decrease was much more dramatic with culture techniques than with qPCR. On the contrary, the concentrations of culturable E. faecium(T) were stable. CONCLUSIONS: The results suggest that the cells of L. monocytogenes strain Scott A might have entered a viable, but nonculturable (VBNC) status, whereas cells of the indicator bacteria, E. faecium(T), maintained themselves better and stayed culturable. SIGNIFICANCE AND IMPACT OF THE STUDY: The difference of survival kinetics in the sludge of a faecal indicator (E. faecium) and a pathogenic bacterium (L. monocytogenes) may be linked to the fact that they either enter or do not enter into a VBNC status.
Asunto(s)
Enterococcus faecium/crecimiento & desarrollo , Listeria monocytogenes/crecimiento & desarrollo , Aguas del Alcantarillado/microbiología , Toxinas Bacterianas/genética , Recuento de Colonia Microbiana , ADN Bacteriano/genética , Heces/microbiología , Proteínas de Choque Térmico/genética , Proteínas Hemolisinas , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genéticaRESUMEN
Chronic obstructive pulmonary disease (COPD) and asthma are conditions that exact a tremendous toll on patients, providers, and society. The substantial increase in the prevalence of both conditions in recent decades has generated sizable concern from both domestic and global perspectives. The underlying characteristics of both conditions involve inflammation of the respiratory tract, although the specific nature and reversibility of these processes differ according to each illness. Within the context of disease management, acute exacerbations are important clinical events that contribute to an increase in morbidity and mortality, and may occur in any patient suffering from the disease. Because these conditions are highly important to clinical practice and healthcare systems, this article will highlight key aspects of epidemiology, burden of illness, and clinical presentation of COPD and asthma. A review of the definition, classification, and natural history is also offered, emphasizing the role of acute exacerbations. In general, the natural history of both COPD and asthma is highly variable and not precisely defined because of their heterogeneous clinical courses. Continued inquiry concerning the epidemiology, etiology, classification, and prognosis of each condition and related exacerbations may offer clinicians improved decision-making information to optimize interventions for affected patient populations.
Asunto(s)
Asma/epidemiología , Costo de Enfermedad , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Asma/economía , Humanos , Enfermedad Pulmonar Obstructiva Crónica/economía , Estados UnidosRESUMEN
Acute exacerbations in chronic obstructive pulmonary disease (COPD) and asthma are potentially life-threatening clinical events that may result in substantial morbidity and mortality. Treatment of these episodes requires the rapid reversal of airway obstruction by decreasing bronchoconstriction and inflammation. Consensus guidelines and recommendations build on stepwise approaches to care, with the mainstay of therapeutic interventions involving brochodilators and often including systemic corticosteroids, oxygen, and other treatments, depending on severity and setting. Future therapies that target inflammatory processes may offer improved efficacy and potential disease-modifying effects. The purpose of this article is to assess the treatment options for acute exacerbations in COPD and asthma within the scope of current consensus guidelines and recommendations (eg, Global Initiative for Chronic Obstructive Lung Disease, National Asthma Education and Prevention Program, Global Initiative for Asthma). Although bronchodilators and corticosteroids are the primary therapies discussed, antibiotics, oxygen, magnesium sulfate, noninvasive positive pressure ventilation, and helium/oxygen mixtures are also addressed. Preventive approaches for future exacerbations are considered in the overall approach to achieve optimal outcomes.