RESUMEN
DLC-1 was originally identified as a potential tumor suppressor. One of the key biochemical functions of DLC-1 is to serve as a GTPase activating protein (GAP) for members of the Rho family of GTPases, particularly Rho A-C and Cdc 42. Since these GTPases are critically involved in regulation of the cytoskeleton and cell migration, it seems clear that DLC-1 will also influence these processes. In this review we examine basic aspects of the actin cyoskeleton and how it relates to cell motility. We then delineate the characteristics of DLC-1 and other members of its family, and describe how they may have multiple effects on the regulation of cell polarity, actin organization, and cell migration.
Asunto(s)
Citoesqueleto/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Supresoras de Tumor/fisiología , Animales , Movimiento Celular , Humanos , Ratones , Modelos Biológicos , Invasividad Neoplásica , Metástasis de la Neoplasia , Transducción de Señal , Proteínas Supresoras de Tumor/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Proteína de Unión al GTP rhoB/metabolismo , Proteína rhoC de Unión a GTPRESUMEN
OBJECTIVE: To study the risk factors for gastrointestinal complications related to enteral nutrition in critically ill children. DESIGN: A prospective, observational study. SETTING: Pediatric intensive care unit. SUBJECTS: Five hundred and twenty-six critically ill children who received transpyloric enteral nutrition(TEN). METHODS: Univariate and multivariate logistic regression analysis were used to identify risk factors for gastrointestinal complications. RESULTS: Sixty six patients (11.5%) presented gastrointestinal complications, 33 (6.2%) abdominal distension and/or excessive gastric residue, 34 (6.4%) diarrhea, one gastrointestinal bleeding, three necrotizing enterocolitis and one duodenal perforation. Enteral nutrition was definitively suspended because of gastrointestinal complications in 11 (2.1%) patients. Fifty patients (9.5%) died. Gastrointestinal complications were more frequent in the patients who died. Death was related to complications of the nutrition in only one patient. The frequency of gastrointestinal complications was significantly higher in children with shock, acute renal failure, hypokalemia, hypophosphatemia and in those receiving dopamine, epinephrine and vecuronium. The stepwise multivariate logistic regression analysis showed that the most important factors associated with gastrointestinal complications were shock, epinephrine at a rate higher than 0.3 microg/kg/min and hypophosphatemia. CONCLUSIONS: The tolerance of TEN in critically ill children is good, although the incidence of gastrointestinal complications is higher in patients with shock, acute renal failure, hypokalemia, hypophosphatemia, and those receiving epinephrine, dopamine, and vecuronium.
Asunto(s)
Enfermedad Crítica/terapia , Nutrición Enteral/efectos adversos , Enfermedades Gastrointestinales/etiología , Complicaciones Posoperatorias/etiología , Lesión Renal Aguda/complicaciones , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crítica/mortalidad , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/mortalidad , Humanos , Hipopotasemia/complicaciones , Hipofosfatemia/complicaciones , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Píloro , Factores de Riesgo , Choque/complicaciones , Factores de Tiempo , Resultado del TratamientoRESUMEN
The objective of this study was to determine the prevalence of antibodies against alpha-fodrin (alpha-fodrin) of the immunoglobulin G (IgG) isotype in Sjögren's syndrome (SS), as defined by European Community Study Group (ESG) and ESG-modified criteria. We arrived at the prevalence and mean concentrations of IgG anti-alpha-fodrin antibodies using enzyme-linked immunosorbent assay (ELISA) in 507 patients with SS, primary SS (pSS), and secondary SS (sSS), classified according to either the ESG or the ESG-modified criteria. IgG anti-alpha-fodrin antibodies were detected in 6/507 (1.2%) and 4/228 (1.7%) of the SS group, according to the ESG or ESG-modified criteria, respectively. Similar prevalence was found for patients with pSS or sSS. Anti-Ro/SSA antibodies were present in 151/409 (36.9%) vs. 149/213 (70.0%) of the SS group, 85/195 (43.6%) vs. 83/101 (82.2%) of the pSS group, and 66/214 (30.8%) vs. 66/112 (58.9%) of the sSS group. Anti-La/SSB antibodies were detected in 77/403 (19.1%) vs. 73/212 (34.4%) of the SS group, 47/194 (24.2%) vs. 45/101 (44.5%) of the pSS group, and 30/209 (14.3%) vs. 28/111 (25.2%) of the sSS group. No clinical associations were found. Only two IgG anti-alpha-fodrin-positive sera were anti-Ro/SSA-negative. We conclude that IgG antibodies against alpha-fodrin are present in a small percentage of people with SS, pSS, and sSS. The lower prevalence in patients classified according to the ESG criteria reflects the lower specificity of these criteria. IgG anti-alpha-fodrin antibodies can be detected in some SS patients whose sera do not contain anti-Ro/SSA antibodies.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Proteínas Portadoras/análisis , Inmunoglobulina G/análisis , Proteínas de Microfilamentos/análisis , Prevalencia , Síndrome de Sjögren/epidemiología , Síndrome de Sjögren/inmunología , Anticuerpos Antinucleares/análisis , Ensayo de Inmunoadsorción Enzimática , Humanos , Síndrome de Sjögren/clasificación , Síndrome de Sjögren/fisiopatología , España/epidemiologíaRESUMEN
The demolition of a maternity building at our institution provided us with the opportunity to study the load of filamentous fungi in the air. External (nearby streets) and internal (within the hospital buildings) air was sampled with an automatic volumetric machine (MAS-100 Air Samplair) at least daily during the week before the demolition, at 10, 30, 60, 90,120, 180, 240, 420, 540 and 660 min post-demolition, daily during the week after the demolition and weekly during weeks 2, 3 and 4 after demolition. Samples were duplicated to analyse reproducibility. Three hundred and forty samples were obtained: 115 external air, 69 'non-protected' internal air and 156 protected internal air [high efficiency particulate air (HEPA) filtered air under positive pressure]. A significant increase in the colony count of filamentous fungi occurred after the demolition. Median colony counts of external air on demolition day were significantly higher than from internal air (70.2 cfu/m(3) vs 35.8 cfu/m(3)) (P < 0.001). Mechanical demolition on day +4 also produced a significant difference between external and internal air (74.5 cfu/m(3) vs 41.7 cfu/m(3)). The counts returned to baseline levels on day +11. Most areas with a protected air supply yielded no colonies before demolition day and remained negative on demolition day. The reproducibility of the count method was good (intra-assay variance: 2.4 cfu/m(3)). No episodes of invasive filamentous mycosis were detected during the three months following the demolition. Demolition work was associated with a significant increase in the fungal colony counts of hospital external and non-protected internal air. Effective protective measures may be taken to avoid the emergence of clinical infections.
Asunto(s)
Microbiología del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Recuento de Colonia Microbiana/métodos , Monitoreo del Ambiente/métodos , Explosiones , Hongos , Arquitectura y Construcción de Hospitales , Aire Acondicionado/instrumentación , Aire Acondicionado/métodos , Recuento de Colonia Microbiana/instrumentación , Recuento de Colonia Microbiana/normas , Infección Hospitalaria/epidemiología , Infección Hospitalaria/etiología , Monitoreo del Ambiente/instrumentación , Monitoreo del Ambiente/normas , Monitoreo Epidemiológico , Filtración/instrumentación , Filtración/métodos , Hongos/crecimiento & desarrollo , Arquitectura y Construcción de Hospitales/métodos , Maternidades , Hospitales de Enseñanza , Humanos , Control de Infecciones , Diseño Interior y Mobiliario , Micosis/epidemiología , Micosis/etiología , España/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: Regional bone loss in patients who have a spinal cord injury has been evaluated in males. In addition, there have been reports on groups of patients of both genders who had an acute or chronic complete or incomplete spinal cord injury. Regional bone loss in females who have a complete spinal cord injury has not been reported, to our knowledge. METHODS: In a study of thirty-one women who had a chronic, complete spinal cord injury, we assessed bone mineral density in relation to age, weight, and time since the injury. The results were compared with the bone mineral density in seventeen healthy, able-bodied women who had been age-matched by group (thirty years old and less, thirty-one to fifty years old, and more than fifty years old). Dual-energy x-ray absorptiometry was used to measure the bone mineral density of the lumbar spine, hip, and knee; Z-scores for the hip and spine were calculated. RESULTS: The mean bone mineral density in the spine in the youngest, middle, and oldest spinal-cord-injury groups was 98%, 108%, and 115% of the densities in the respective age-matched control groups (p < 0.0001), and the mean bone mineral density in the oldest spinal-cord-injury group was equal to that in the youngest control group. This gain in bone mineral density in the spine was reflected by the spine Z-scores, as the mean score in the oldest injured group averaged more than one standard deviation above both the norm and the mean score in the control group. The mean loss of bone mineral density in the knee in the youngest, middle, and oldest spinal-cord-injury groups was 38%, 41%, and 47% compared with the densities in the corresponding control age-groups (p < 0.0001). Furthermore, the oldest injured group had a mean reduction of knee bone mineral density of 54% compared with the youngest control group. The mean loss of bone mineral density in the hips of the injured patients was 18%, 25%, and 25% compared with the densities in the control subjects in the respective age-groups (p < 0.0001). CONCLUSIONS: The bone mineral density in the spine either was maintained or was increased in relation to the time since the injury. This finding is unlike that seen in healthy women, in whom bone mineral density decreases with age. The bone mineral density in the hips of the injured patients initially decreased approximately 25%; thereafter, the rate of loss was similar to that in the control group. The bone mineral density in the knees of the injured patients rapidly decreased 40% to 45% and then further decreased only minimally.
Asunto(s)
Osteoporosis/etiología , Traumatismos de la Médula Espinal/complicaciones , Absorciometría de Fotón , Adulto , Densidad Ósea , Femenino , Cadera/fisiopatología , Humanos , Rodilla/fisiopatología , Persona de Mediana Edad , Osteoporosis/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Columna Vertebral/fisiopatologíaRESUMEN
Chart reviews were used to describe demographic and clinical characteristics of 68 urban American Indian people attending an Indian-oriented outpatient substance-abuse treatment program in Denver, Colorado, and to describe program staff's assessment of client's response to treatment. Alcohol and marijuana were the drugs abused most frequently. The program admitted about equal numbers of males and females; age averaged 24 years. Although Colorado has only Ute reservations, 49% of clients were Sioux, while none were Ute. Moreover, 87% of clients were not active in Indian religion and culture. Clients had low educational achievement and very low income. Few were in stable marriages. In comparison to counselors, clients underestimated the severity of their problems. By counselors' assessment, 78% of clients did not finish the program, and only two fully achieved the treatment goals. Areas for further clinical research are suggested.
Asunto(s)
Alcoholismo/rehabilitación , Indígenas Norteamericanos/psicología , Trastornos Relacionados con Sustancias/rehabilitación , Población Urbana , Adolescente , Adulto , Alcoholismo/psicología , Colorado , Femenino , Estudios de Seguimiento , Humanos , Masculino , Abuso de Marihuana/psicología , Abuso de Marihuana/rehabilitación , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
DLC1 (deleted in liver cancer 1), which encodes a Rho GTPase-activating protein (Rho-GAP), is a potent tumor suppressor gene that is frequently inactivated in several human cancers. DLC1 is a multidomain protein that has been shown previously to bind members of the tensin gene family. Here we show that p120Ras-GAP (Ras-GAP; also known as RASA1) interacts and extensively colocalizes with DLC1 in focal adhesions. The binding was mapped to the SH3 domain located in the N terminus of Ras-GAP and to the Rho-GAP catalytic domain located in the C terminus of the DLC1. In vitro analyses with purified proteins determined that the isolated Ras-GAP SH3 domain inhibits DLC1 Rho-GAP activity, suggesting that Ras-GAP is a negative regulator of DLC1 Rho-GAP activity. Consistent with this possibility, we found that ectopic overexpression of Ras-GAP in a Ras-GAP-insensitive tumor line impaired the growth-suppressing activity of DLC1 and increased RhoA activity in vivo. Our observations expand the complexity of proteins that regulate DLC1 function and define a novel mechanism of the cross talk between Ras and Rho GTPases.1R01CA129610
Asunto(s)
Neoplasias/patología , Proteínas Supresoras de Tumor/fisiología , Proteína Activadora de GTPasa p120/fisiología , Proteína de Unión al GTP rhoA/metabolismo , Dominio Catalítico , Línea Celular Tumoral , Proliferación Celular , Proteínas Activadoras de GTPasa , Humanos , Proteínas Supresoras de Tumor/análisis , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Proteínas Supresoras de Tumor/química , Proteína Activadora de GTPasa p120/análisis , Proteína Activadora de GTPasa p120/química , Dominios Homologos srcRESUMEN
El personal sanitario se encuentra incluido cada año entre los grupos de riesgo con indicación para vacunarse frente a la gripe. No obstante, las coberturas vacunales entre el personal sanitario en nuestro país son muy bajas, no superando el 25%. Convencidos de que una de las mejores herramientas para aumentar estas coberturas entre los profesionales de nuestro país son las evidencias científicas, 19 Sociedades Científicas y Asociaciones Profesionales que agrupan a los profesionales sanitarios más directamente relacionados con la gripe como problema de salud, así como el Consejo General de Enfermería, se han reunidopara debatir y elaborar este documento de consenso con el objetivo de concienciar al personal sanitario sobre la conveniencia de su vacunación frente a la gripe y de los beneficios que de ella se derivan para sí mismos, para sus pacientes y para el resto de la población. Esta recomendación está basada en 3 pilares básicos: argumento de necesidad, de ética y de ejemplaridad
Health care workers (HCW) are included each year among risk groups for vaccination against influenza. However, vaccination coverage among this group in our country is very low, not exceeding 25%. Convinced that one of the best tolos to increase this coverage among professionals in our country are the scientific evidence, 19 scientific societies and associations professionals bringing together health professionals more directly related to influenza as an health problem, and the General Nursing Council, met to discuss and develop this consensus document in order to inform HCW about the appropriateness of their vaccination against influenza and the benefits that flow from it for themselves, for their patients and for the rest of the population. This recommendation is based on 3 pillars: argument of necessity, ethics and exemplary
Asunto(s)
Humanos , Vacunación/normas , Gripe Humana/prevención & control , Cobertura de Vacunación , Personal de Salud/estadística & datos numéricosRESUMEN
Assessment of strength using motor scores derived from the standards of the American Spinal Injury Association (ASIA) was compared with assessment using motor scores based on biomechanical aspects of walking in the prediction of ambulatory performance. Measurements of strength, gait performance, and the energy expenditure were performed in 36 spinal cord injured patients. The ASIA scoring system compared favorably with the biomechanical scoring system. The ASIA score strongly correlated with the percent increase in the rate of O2 consumption above normal (p < .0005), O2 cost per meter (p < .0006), peak axial load exerted by the arms on crutches (p < .0001), velocity (p < .0001), and cadence (p < .0001). Patients with lower extremity ASIA scores < or = 20 were limited ambulators with slower average velocities at higher heart rates, greater energy expenditure, and greater peak axial load exerted on assistive devices than patients with lower extremity ASIA scores > or = 30 who were community ambulators. We conclude the ASIA motor score is a simple clinical measure that strongly correlates with walking ability.
Asunto(s)
Evaluación de la Discapacidad , Locomoción , Músculos/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Adulto , Fenómenos Biomecánicos , Metabolismo Energético , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Análisis de Regresión , Traumatismos de la Médula Espinal/clasificaciónRESUMEN
We measured the cervical length of 166 normal, gravid patients between 8 and 37 weeks' gestation by vaginal ultrasonography. Patients were assigned to one of five groups according to gestational age at the time of the measurements. Cervical length was longest (48 mm) in group 3 (20 to 25 weeks) and significantly longer than that of groups 1 (8 to 13 weeks), 2 (14 to 19 weeks), and 5 (32 to 37 weeks). The use of vaginal ultrasonography to assess cervical length eliminates some technical problems encountered with abdominal ultrasonography. Nomogram of cervical length throughout pregnancy was established. This may aid in early diagnosis and management of preterm labor and cervical incompetence.
Asunto(s)
Cuello del Útero/anatomía & histología , Embarazo/fisiología , Ultrasonografía/métodos , Femenino , Humanos , Vagina/anatomía & histologíaRESUMEN
Molecular dynamics studies of the N-domain (amino acids 1-77; CaM(1-77)) of Ca2+-loaded calmodulin (CaM) show that a solvent exposed hydrophobic cleft in the crystal structure of CaM exhibits transitions from an exposed (open) to a buried (closed) state over a time scale of nanoseconds. As a consequence of burying the hydrophobic cleft, the R(g) of the protein is reduced by 1.5 A. Based on this prediction, x-ray scattering experiments were conducted on this domain over a range of concentrations. Models built from the scattering data show that the R(g) and general shape is consistent with the simulation studies of CaM(1-77). Based on these observations we postulate a model in which the conformation of CaM fluctuates between two different states that expose and bury this hydrophobic cleft. In aqueous solution the closed state dominates the population, while in the presence of peptides, the open state dominates. This inherent flexibility of CaM may be the key to its versatility in recognizing structurally distinct peptide sequences. This model conflicts with the currently accepted hypothesis based on observations in the crystal structure, where upon Ca2+ binding the hydrophobic cleft is exposed to solvent. We postulate that crystal packing forces stabilize the protein conformation toward the open configuration.
Asunto(s)
Calmodulina/química , Fenómenos Biofísicos , Biofisica , Calcio/química , Calcio/metabolismo , Simulación por Computador , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Metionina/química , Modelos Moleculares , Modelos Teóricos , Unión Proteica , Conformación Proteica , Estructura Terciaria de Proteína , Dispersión de Radiación , Factores de Tiempo , Agua/química , Agua/metabolismo , Rayos XRESUMEN
This study compares the correlation between two methods for the determination of cardiac output-the pulmonary arterial thermodilution technique using the Swan-Ganz catheter and the femoral arterial thermodilution technique using a pulse contour analysis computer (PiCCO) catheter. We performed a prospective animal study using 16 immature Maryland pigs weighing 9 to 16 kg. A 5.5- or 7.5-Fr Swan-Ganz catheter was introduced into the femoral or jugular vein, and a 4- or 5-Fr arterial PiCCO catheter was introduced into the femoral artery. In each animal, we made measurements of cardiac output at 30-minute intervals, simultaneously by pulmonary arterial thermodilution and femoral arterial thermodilution, before, during, and after hemodiafiltration carried out via different venous catheters, recording a total of 78 measurements. The mean Swan-Ganz cardiac output was 2.22 +/- 0.94 L/min, and mean PiCCO cardiac output was 1.94 +/- 0.80 L/min (no significant difference). The mean difference (bias) of differences (limits of agreement) was 0.2812. The differences between the methods increased with higher cardiac output, but the percentage differences in relation to cardiac output remained stable. Good correlation was found between the two methods: single-measure intraclass correlation was 0.8892 (95% confidence interval, 0.54-0.95). There were no differences between the 5.5- and 7.5-FR Swan-Ganz catheters or between the 4- and 5-Fr PiCCO catheters. Femoral arterial thermodilution cardiac output measurements correlated well with pulmonary arterial thermodilution cardiac output measurements in a pediatric animal model.