RESUMEN
Obesity affects more than 35% of Americans, increasing the risk of more than 200 comorbid conditions, impaired quality of life and premature mortality. This review aimed to summarize literature published over the past 15 years regarding the prevalence and impact of obesity in people with haemophilia (PWH) and to discuss implementing general guidelines for weight management in the context of the haemophilia comprehensive care team. Although few studies have assessed the effects of obesity on haemophilia-specific outcomes, existing evidence indicates an important impact of weight status on lower extremity joint range of motion and functional disability, with potentially important effects on overall quality of life. Data regarding bleeding tendency in PWH with coexisting obesity are largely inconclusive; however, some individuals may experience reduced joint bleeds following moderate weight loss. Additionally, conventional weight-based dosing of factor replacement therapy leads to increased treatment costs for PWH with obesity or overweight, suggesting pharmacoeconomic benefits of weight loss. Evidence-based recommendations for weight loss include behavioural strategies to reduce caloric intake and increase physical activity, pharmacotherapy and surgical therapy in appropriate patients. Unique considerations in PWH include bleed-related risks with physical activity; thus, healthcare professionals should advise patients on types and intensities of, and approaches to, physical activity, how to adjust treatment to accommodate exercise and how to manage potential activity-related bleeding. Increasing awareness of these issues may improve identification of PWH with coexisting obesity and referral to appropriate specialists, with potentially wide-ranging benefits in overall health and well-being.
Asunto(s)
Hemofilia A/fisiopatología , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Comorbilidad , Ejercicio Físico/fisiología , Guías como Asunto , Hemofilia A/epidemiología , Hemofilia A/terapia , Humanos , Obesidad/epidemiología , Obesidad/terapia , Sobrepeso/epidemiología , Sobrepeso/terapia , Prevalencia , Estados Unidos/epidemiología , Pérdida de Peso/fisiologíaAsunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Enfermedades del Sistema Inmune/terapia , Acondicionamiento Pretrasplante , Niño , Insuficiencia de Crecimiento/diagnóstico , Insuficiencia de Crecimiento/genética , Insuficiencia de Crecimiento/terapia , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/genética , Masculino , Síndrome , Trasplante HomólogoRESUMEN
Most of the completely sequenced prokaryotic genomes contain genes of potassium channel homologues, but there is still not much known about the role of these proteins in prokaryotes. Here we describe the large-scale overproduction and purification of a prokaryotic voltage-gated potassium channel homologue, Kch, from Escherichia coli. After successful overproduction of the protein, a specific increase in the potassium permeability of the cells was found. Kch could be purified in large amounts using classical purification methods to prevent aggregation of the protein. The physiological state of the protein was revealed to be a homotetramer and the protein was shown to be localized to the cytoplasmic membrane of the cells. In the course of the localization studies, we found a specific increase in the density of the cytoplasmic membrane on Kch production. This was linked to the observed increase in the protein to lipid ratio in the membranes. Another observed change in the membrane composition was an increase in the cardiolipin to phosphatidylglycerol ratio, which may indicate a specific cardiolipin requirement of Kch. On the basis of some of our results, we discuss a function for Kch in the maintenance of the membrane potential in E. coli.
Asunto(s)
Escherichia coli , Activación del Canal Iónico , Canales de Potasio/química , Canales de Potasio/metabolismo , Membrana Celular/química , Membrana Celular/ultraestructura , Dicroismo Circular , Escherichia coli/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/aislamiento & purificación , Proteínas de Escherichia coli/metabolismo , Potasio/metabolismo , Canales de Potasio/genética , Canales de Potasio/aislamiento & purificación , Estructura Cuaternaria de Proteína , Estructura Secundaria de Proteína , Proteínas Recombinantes , Solubilidad , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
The natural history of chronic hepatitis C (HCV) infections in long-term leukemia survivors has not been well characterized. We studied the prevalence of HCV infections, measured HCV RNA levels, and evaluated the severity of liver disease in patients with leukemia who achieved long-term remissions after intensive chemotherapy or bone marrow transplantation (BMT). HCV antibody tests were performed by the enzyme-linked immunosorbent assay (ELISA) and positive tests confirmed by the recombinant immunoblot assay (RIBA). HCV RNA levels were measured by the branched DNA (bDNA) assay. Seventy-five leukemia survivors with 25 or more blood donor exposures were identified. Nine (12%) were anti-HCV positive. All were infected before 1992 when second generation HCV screening tests were implemented. Mean HCV RNA levels were 10.3 x10(6) eq/mL versus 3.2 x 10(6) eq/mL (P =.056) in a control group of 20 anti-HCV positive immunocompetent individuals of comparable age who were infected twice as long (17.8 +/- 6.5 years v 9.0 +/- 4.4 years in leukemia survivors, P =.001). Liver biopsies were performed on six of the nine anti-HCV positive leukemia survivors. All showed at least moderate portal inflammation and half had evidence of bridging fibrosis. We conclude that viral loads in anti-HCV positive leukemia survivors are markedly higher than in immunocompetent controls. Our results suggest that long-term leukemia survivors with chronic HCV may have more rapidly progressive liver disease than has been previously recognized.
Asunto(s)
Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/etiología , Leucemia/complicaciones , Leucemia/virología , Adulto , Niño , Estudios de Cohortes , Femenino , Hepatitis C Crónica/fisiopatología , Hepatitis C Crónica/virología , Humanos , Leucemia/fisiopatología , Leucemia/terapia , Masculino , Persona de Mediana Edad , Prevalencia , Reacción a la Transfusión , Carga ViralRESUMEN
Autophonia, the hyperperception of one's own voice and breathing, is one of the consequences of rapid weight loss and is explained within the syndrome of the patulous eustachian tube. We report on a female adolescent, who presented to an otologist for autophonia and was finally diagnosed with anorexia nervosa. The occurrence and relevance of this symptom in eating-disorder patients is discussed.
Asunto(s)
Anorexia Nerviosa/complicaciones , Enfermedades del Oído/etiología , Trompa Auditiva , Trastornos de la Audición/etiología , Adolescente , Trompa Auditiva/fisiopatología , Femenino , HumanosRESUMEN
For neuromuscular patients with progressive respiratory muscle weakness a new training apparatus was developed, which allows a home training of strength as well as endurance of the inspiratory muscles, especially the diaphragma. A significant positive training result could be proved in a comparative study between 2 groups of 15 Duchenne muscular dystrophy (DMD) patients each (8). By the end of the training the satisfaction of patients with the new training equipment was evaluated by means of a questionnaire. The degree of satisfaction was determined at a 10-point scale. Critical ideas were used for improvement of the newly developed training apparatus.
Asunto(s)
Distrofias Musculares/rehabilitación , Satisfacción del Paciente , Insuficiencia Respiratoria/rehabilitación , Terapia Respiratoria/instrumentación , Rol del Enfermo , Adulto , Niño , Femenino , Humanos , Masculino , Distrofias Musculares/psicología , Cooperación del Paciente/psicología , Insuficiencia Respiratoria/psicología , Terapia Respiratoria/psicología , Resultado del TratamientoRESUMEN
UNLABELLED: The goals of this investigation were to characterize the uptake of 11C-hydroxyephedrine (HED) in neuroblastoma and to determine the feasibility and potential advantages of utilizing this compound as a tumor imaging agent. METHODS: Seven patients with known or subsequently proven neuroblastoma were studied. Each patient underwent PET scanning with 11C-HED. Six of seven patients underwent scintigraphy with [123I]meta-iodobenzylguanidine (MIBG), and two patients were also studied with [18F]FDG PET. For six patients, CT or MR images were available for comparison. RESULTS: Neuroblastomas were located by PET scanning with 11C-HED in all seven patients. The uptake of HED into neuroblastomas was rapid; tumors were evident on images within 5 min postintravenous injection. Those lesions in the field of view of the PET camera were also identified on [123I]MIBG scintigraphic images. In two patients, tumor deposits in the abdomen were better visualized with MIBG scintigraphy due to relatively less hepatic accumulation of MIBG than HED. CONCLUSION: PET scanning with HED for neuroblastoma results in high quality functional images of the tumors that can be obtained within minutes following injection.
Asunto(s)
Efedrina/análogos & derivados , Neuroblastoma/diagnóstico por imagen , Tomografía Computarizada de Emisión , 3-Yodobencilguanidina , Adulto , Radioisótopos de Carbono , Niño , Preescolar , Medios de Contraste , Desoxiglucosa/análogos & derivados , Estudios de Factibilidad , Femenino , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Humanos , Lactante , Radioisótopos de Yodo , Yodobencenos , Masculino , Factores de TiempoRESUMEN
PURPOSE: To assess the uptake of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in common and uncommon tumors in children and to develop a method for performing positron emission tomography (PET) studies in children with malignant neoplasms. MATERIALS AND METHODS: Twenty-two pediatric patients with known or suspected malignancies (27 scans) underwent FDG PET. Tumor uptake of FDG was measured on PET scans. RESULTS: Tumor uptake of FDG was detected in 17 of 21 patients with malignant disease. Neuroblastomas and their metastases (including those that did not absorb metaiodobenzylguanidine) intensely accumulated FDG. In a patient with Ewing sarcoma, FDG PET showed two foci of metastatic disease not evident on bone scans. In two patients, PET showed that large areas of the tumor were necrotic. CONCLUSION: FDG PET is feasible, is useful in the study of tumors in children, and may provide unique, clinically important information.
Asunto(s)
Desoxiglucosa/análogos & derivados , Neoplasias/diagnóstico por imagen , Tomografía Computarizada de Emisión , Adolescente , Niño , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Humanos , Lactante , Linfoma/diagnóstico por imagen , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/secundario , Sarcoma de Ewing/diagnóstico por imagen , Sarcoma de Ewing/secundarioRESUMEN
BACKGROUND: The 27-kd heat shock protein (Hsp27) is differentially expressed in some malignancies, including breast carcinoma, leukemia, and malignant fibrous histiocytoma. In breast carcinoma, a high-level expression of Hsp27 has been associated with shorter disease-free survival in patients with localized disease. PURPOSE: We have observed variable levels of Hsp27 among neuroblastoma tumors. Our aim in this study was to investigate the relationship between Hsp27 expression and stage of the disease and N-myc gene copy number. METHODS: We determined Hsp27 protein levels in 53 neuroblastoma tumors representing different stages of the disease and in 17 neuroblastoma cell lines by quantitative two-dimensional polyacrylamide gel electrophoresis (PAGE). We also performed statistical analysis of Hsp27 levels in relation to stage of the disease and to N-myc gene copy number. RESULTS: Increased Hsp27 expression in neuroblastomas was associated with limited stage disease and inversely correlated with N-myc gene amplification, a feature known to predict poor clinical outcome. An inverse correlation was also observed between N-myc gene amplification and Hsp27 protein levels among the neuroblastoma cell lines analyzed. Immunohistochemical staining of sections of neuroblastomas showed that Hsp27 was most prominently expressed in the cytoplasm of large ganglionic tumor cells present in neuronally differentiated areas of the tumors. Induction of neuronal differentiation in SMS-KCNR neuroblastoma cells using retinoic acid resulted in an increase in Hsp27. CONCLUSION: High level expression of Hsp27 in neuroblastoma is a feature of limited stage, differentiated tumors. IMPLICATION: Hsp27 may play a part in the biology of neuroblastomas with a favorable outcome.
Asunto(s)
Expresión Génica , Genes myc , Proteínas de Choque Térmico/análisis , Neuroblastoma/química , Electroforesis en Gel de Poliacrilamida/métodos , Humanos , Inmunohistoquímica , Estadificación de Neoplasias , Neuroblastoma/genética , Neuroblastoma/patología , Células Tumorales CultivadasRESUMEN
Recent evidence suggests that the human interferon-inducible double-stranded RNA-dependent protein kinase may function as a tumor suppressor. Here we describe the mapping of the gene for this kinase to chromosome region 2p21-22 by fluorescence in situ hybridization. A combined analysis of cytogenetic data from a series of 341 patients with hematologic disorders that exhibited cytogenetic abnormalities and from published reports indicates that abnormalities involving 2p21-22 occur nonrandomly and are observed among patients with acute myelogenous leukemia, raising the possibility of a role for this protein kinase in leukemogenesis.
Asunto(s)
Aberraciones Cromosómicas , Trastornos de los Cromosomas , Cromosomas Humanos Par 2 , Interferones/farmacología , Proteínas Serina-Treonina Quinasas/genética , Médula Ósea/enzimología , Médula Ósea/patología , Bandeo Cromosómico , Mapeo Cromosómico , Inducción Enzimática , Femenino , Enfermedades Hematológicas/genética , Humanos , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/genética , Masculino , Proteínas Serina-Treonina Quinasas/biosíntesis , eIF-2 QuinasaRESUMEN
We have developed a data base of lymphoid proteins detectable by two-dimensional polyacrylamide gel electrophoresis. The data base contains two-dimensional patterns and derived information pertaining to polypeptide constituents of unstimulated and stimulated mature T cells and immature thymocytes, single-cell-derived T- and B-cell clones, leukemia cells, and lymphoid cell lines. Using this data base, we have compared the protein constituents of mature T cells and immature thymocytes before and after mitotic stimulation. A subset of polypeptides that are induced in mature T cells following mitotic stimulation were found to be constitutively expressed in immature thymocytes. Other polypeptides exhibited differences in their expression between mature and immature thymocytes in a manner unrelated to proliferation. The identity of several constitutively expressed or mitotically induced proteins in lymphoid cells was established by microsequencing. These initial findings point to significant differences in the molecular pathways leading to proliferation between mature and immature T cells. The construction of this database should facilitate further studies of lymphoid differentiation and function.
Asunto(s)
Bases de Datos Factuales , Activación de Linfocitos , Proteínas/genética , Linfocitos T/fisiología , Timo/fisiología , Secuencia de Aminoácidos , Antígenos CD4/análisis , Antígenos CD8/análisis , Diferenciación Celular , Preescolar , Electroforesis en Gel Bidimensional , Enzimas/genética , Humanos , Datos de Secuencia Molecular , Proteínas/aislamiento & purificación , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/fisiología , Linfocitos T/citología , Linfocitos T/inmunología , Timo/inmunologíaRESUMEN
Op18 is a highly conserved major cytosolic phosphoprotein which has been implicated in signal transduction in a wide variety of cell types. Freshly isolated peripheral blood lymphocytes (PBL) constitutively express low levels of mostly unphosphorylated Op18. Following mitogenic stimulation of PBL, Op18 synthesis is induced at a time when cells are entering S-phase. In this study we have characterized Op18 phosphorylation during progression of freshly isolated PBL through the cell cycle. Transition from G0 to G1 following activation with OKT3 was associated with an increase in a phosphorylated form designated Op18c. Progression of cells through G1 into S resulted in an increase in phosphorylated Op18 forms, designated Op18a and Op18b, which paralleled new Op18 synthesis. Transition of cells into G2 + M resulted in the appearance of the more acidic phosphorylated forms Op18d and Op18e. Calphostin C, a specific inhibitor of protein kinase C, dramatically decreased all forms of phosphorylated Op18 in OKT3 treated Jurkat cells. Our results suggest that Op18 phosphorylation is mediated in part by PKC activation as well as by other kinases yielding different phosphorylated forms at specific stages of the cell cycle.