RESUMEN
Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.
Asunto(s)
Acalasia del Esófago/diagnóstico , Acalasia del Esófago/terapia , Adulto , Toxinas Botulínicas/uso terapéutico , Niño , Dilatación/métodos , Dilatación/normas , Manejo de la Enfermedad , Acalasia del Esófago/fisiopatología , Esofagoscopía/métodos , Esofagoscopía/normas , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Miotomía/métodos , Miotomía/normas , Factores de Riesgo , Índice de Severidad de la Enfermedad , Evaluación de Síntomas/métodos , Evaluación de Síntomas/normasRESUMEN
Omi is a human serine protease whose catalytic domain is homologous to a bacterial heat shock endoprotease (HtrA), a protein indispensable to the survival of bacteria at elevated temperatures. Omi is expressed ubiquitously, and its protein product is predominantly localized in the endoplasmic reticulum of mammalian cells. Here we present the genomic structure of Omi, consisting of eight exons located on human chromosome 2p12-p13. Furthermore, we describe an alternatively splice form of Omi (D-Omi) that is expressed predominantly in the kidney, colon, and thyroid. D-Omi lacks peptide sequence encoded by two exons (exons III and VII). The absence of exon VII leads to a protein with a modified PDZ domain unable to interact with a known partner, the Mxi2 protein. The absence of exon III affects the catalytic domain and leads to a protein with no detectable protease activity. Our studies suggest that D-Omi may have a unique role in the normal function of kidney, colon, and thyroid.
Asunto(s)
Cromosomas Humanos Par 2 , Proteínas Periplasmáticas , Empalme del ARN , Serina Endopeptidasas/genética , Secuencia de Aminoácidos , Mapeo Cromosómico , Exones , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Serina Peptidasa A2 que Requiere Temperaturas Altas , Humanos , Proteínas Mitocondriales , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismoRESUMEN
BACKGROUND: To study the effects of plasma-exchange on removal and recovery of haemostatic factors and inhibitors using albumin or PPS as replacement fluid. DESIGN: Prospective, noninterventional study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: The study included 11 consecutive patients with Myasthenia Gravis, whose haemostatic parameters were normal before plasma-exchange. INTERVENTIONS: Plasma coagulative factors and inhibitors were studied before at the end of and 24 hours after each exchange. RESULTS: Immediately after exchange plasma coagulation factors and inhibitors evaluated were reduced, except for factor VIII; 24 hours later only fibrinogen was significantly decreased; D-Dimer was not found increased; the platelets, after exchange, were at normal levels. CONCLUSIONS: Our data show a parallel lowering of haemostatic factors and inhibitors after plasmapheresis using material devoid of coagulation factors as replacement, this explains the absence of hemorrhagic or thrombotic complications. So we think that careful monitoring of coagulation during plasma-exchange is not useful.
Asunto(s)
Hemostasis/fisiología , Miastenia Gravis/terapia , Intercambio Plasmático , Humanos , Miastenia Gravis/sangre , Estudios ProspectivosRESUMEN
We report the isolation and characterization of a cDNA encoding the novel mammalian serine protease Omi. Omi protein consists of 458 amino acids and has homology to bacterial HtrA endoprotease, which acts as a chaperone at low temperatures and as a proteolytic enzyme that removes denatured or damaged substrates at elevated temperatures. The carboxyl terminus of Omi has extensive homology to a mammalian protein called L56 (human HtrA), but unlike L56, which is secreted, Omi is localized in the endoplasmic reticulum. Omi has several novel putative protein-protein interaction motifs, as well as a PDZ domain and a Src homology 3-binding domain. Omi mRNA is expressed ubiquitously, and the gene is localized on human chromosome 2p12. Omi interacts with Mxi2, an alternatively spliced form of the p38 stress-activated kinase. Omi protein, when made in a heterologous system, shows proteolytic activity against a nonspecific substrate beta-casein. The proteolytic activity of Omi is markedly up-regulated in the mouse kidney following ischemia/reperfusion.
Asunto(s)
Regulación Enzimológica de la Expresión Génica , Isquemia/genética , Riñón/irrigación sanguínea , Proteínas Periplasmáticas , Serina Endopeptidasas/genética , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Secuencia de Bases , Dominio Catalítico , ADN Complementario , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Serina Peptidasa A2 que Requiere Temperaturas Altas , Humanos , Hidrólisis , Ratones , Proteínas Mitocondriales , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Datos de Secuencia Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Homología de Secuencia de Aminoácido , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismo , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Mxi2 is one of three known alternative spliced forms of the stress-activated mitogen-activated protein kinase p38 (CSBP). Mxi2 was originally identified as a Max-interacting protein and is the smallest member of the family of stress-activated kinases isolated to date. Mxi2 lacks most of the XI domain found in p38 and instead has a distinct COOH-terminal sequence of 17 amino acids. Here we present the genomic structure of the Mxi2/p38 locus on human chromosome 6q21.2/21.3 and establish the origin of the three spliced forms of p38. Using Mxi2-specific antibodies in mouse organs, we found the Mxi2 protein to be present exclusively in the kidney. Mxi2 is present predominantly in the distal tubule of the nephron and the level of the protein decreased during kidney ischemia-reperfusion. Stress signals or other known activators of the p38 pathway including MAP kinase-kinase 3 and MAP kinase-kinase 6 did not induce the kinase activity of Mxi2 using ATF-2 as a substrate. With the use of hybrid proteins encoding different portions of Mxi2 and p38 polypeptides, the different properties of Mxi2 can be assigned to its unique COOH terminus.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Isquemia/metabolismo , Proteínas Quinasas Activadas por Mitógenos , Nefronas/metabolismo , Circulación Renal , Secuencia de Aminoácidos/genética , Animales , Secuencia de Bases/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Línea Celular , Mapeo Cromosómico , ADN Recombinante , Variación Genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Datos de Secuencia Molecular , Proteínas Recombinantes de Fusión/metabolismo , Daño por Reperfusión/metabolismo , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
We describe Mxi2, a human protein that interacts with Max protein, the heterodimeric partner of the Myc oncoprotein. Mxi2 encodes a 297-residue protein whose sequence indicates that it is related to extracellular signal-regulated kinases (ERK protein kinases). Mxi2 in yeast interacts with Max and with the C terminus of c-Myc. Mxi2 phosphorylates Max both in vitro and in vivo. The Mxi2 putative substrate recognition region has sequence similarity to the helix-loop-helix region in Max and c-Myc, suggesting that substrate recognition might be mediated via this motif. Phosphorylation by Mxi2 may affect the ability of Max to oligomerize with itself and its partners, bind DNA, or regulate gene expression.