RESUMEN

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Asunto(s)

Colon/fisiología , Genes Modificadores/genética , Genotipo , Enfermedades Inflamatorias del Intestino/genética , NADPH Oxidasa 1/genética , Animales , Niño , Preescolar , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genoma , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación Missense/genética , Polimorfismo de Nucleótido Simple , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

BACKGROUND: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured. We examined whether IgG-anti-dGli would be useful for diagnosing CD in patients with IgA deficiency. METHODS: We studied 34 IgA-deficient CD patients, 185 IgA-competent newly diagnosed children with CD, 316 children without CD, 400 adult blood donors, and 6 control IgA-deficient individuals without CD. Anti-dGli and anti-tTG were measured by ELISA, and endomysium antibodies (EmA) were measured by immunofluorescence on monkey esophagus (IgA as well as IgG class for all antibodies). We calculated diagnostic sensitivity (percentage of patients above cutoff with 95% CIs) according to age-specific cutoffs for 95% diagnostic specificity and according to cutoffs proposed by the manufacturer of the assays. RESULTS: No IgA-deficient CD patients were positive for any IgA-based antibody assay. Diagnostic sensitivity of IgG-anti-tTG was 91.2% (95% CI 76.3%-97.7%) according to age-specific cutoffs and 82.4% (66.1%-92.0%) according to manufacturer cutoffs. The diagnostic sensitivity of IgG-EmA was 75.8% (58.8%-87.4%) and the sensitivity of IgG-anti-dGli was 88.2% (72.8%-95.9%) according to both cutoffs. CONCLUSIONS: IgG-anti-dGli and IgG-anti-tTG have comparable diagnostic sensitivities for IgA-deficient celiac patients. IgG-anti-dGli may be useful for diagnosing CD in IgA-deficient patients.

Asunto(s)

Enfermedad Celíaca/diagnóstico , Gliadina/inmunología , Deficiencia de IgA/complicaciones , Inmunoglobulina G/inmunología , Adolescente , Adulto , Anciano , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/inmunología , Niño , Preescolar , Femenino , Gliadina/sangre , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Péptidos/sangre , Péptidos/inmunología , Sensibilidad y Especificidad

RESUMEN

Antibodies to deamidated gliadin present a new tool in the diagnosis of celiac disease (CD). In children, the ELISA for the determination of IgG antibodies to (deamidated) gliadin-analogous fusion peptides (GAF3X) has a superior performance compared to the ELISA for the determination of antibodies against native gliadin and is comparable to assays for IgA antibodies against tissue transglutaminase (IgA-anti-tTG). The combined investigation of IgG antibodies to GAF3X (IgG-anti-GAF3X) and IgA-anti-tTG significantly increases the fraction of children definitely identified as either CD or non-CD patients. The new IgG-anti-GAF3X ELISA was also able to detect CD in three cases of IgA deficiency and in two cases of latent CD and was also useful in the diagnosis of children younger than 2 years of age.

Asunto(s)

Autoanticuerpos/sangre , Enfermedad Celíaca/diagnóstico , Gliadina/inmunología , Adolescente , Anticuerpos/sangre , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática/métodos , Gliadina/química , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Lactante , Oligopéptidos/inmunología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Transglutaminasas/inmunología

RESUMEN

Antibody assays play an important role in the diagnosis of coeliac disease (coeliac sprue, gluten-sensitive enteropathy), a condition characterized by immunological intolerance to gluten from wheat and from proteins of related cereals in genetically predisposed persons. Enhanced concentrations of IgA-antibodies against tissue transglutaminase or endomysium under gluten-containing normal diet represent an important indication for a biopsy from the small intestine. Demonstration of typical changes in the mucose of the small intestine is still required for the definitive diagnosis of coeliac disease. Recently highly specific antibodies against deamidated gliadin peptides were detected in serum. These antibodies further improve the reliability of serologic diagnosis. The new assays for IgG-antibodies against deamidated gliadin peptides have a very high diagnostic accuracy and are comparable to IgA tissue transglutaminase antibodies. Further investigations have to show whether IgG-antibodies against deamidated gliadin peptides are a reliable disease marker also in case of IgA deficiency. Prospective studies are needed to show whether antibody assays could replace biopsy in the diagnosis of coeliac disease in a substantial number of patients.

Asunto(s)

Autoanticuerpos/análisis , Enfermedad Celíaca/diagnóstico , Inmunoglobulina A/análisis , Inmunoglobulina G/sangre , Intestino Delgado/patología , Autoanticuerpos/sangre , Biopsia , Enfermedad Celíaca/inmunología , Gliadina/inmunología , Humanos , Mucosa Intestinal/patología , Fibras Musculares Esqueléticas/inmunología , Fragmentos de Péptidos/inmunología , Transglutaminasas/inmunología

RESUMEN

Physical interactions between different cell types are a requirement for the initiation and maintenance of immune responses. The distribution pattern of cells within a tissue may result from specific cell-cell-interactions or random distribution. Tissue architecture, degree of inflammation, frequencies of cells, number of contact partners, cell type, and size as well as cell movement and contact time determine the distribution of cells within tissues. We developed a matrix model to determine the degree of expected random distribution of two cell types (A and B) and cell-cell-contacts within tissue sections. The model predictions were compared with experimental data derived from immunofluorescence microscopy. We implemented a computer algorithm for automatic image analysis to visualize and quantify cell-cell-neighborhood relations. Using the number of cells type A (a), the total cell number (t) and the mean number of cells that are in contact with cells type B (c(B)), the ratio of cells type B in contact with cells type A can be described by b(A)/b = 1- (1- (a/t))[symbol: see text]c(B). We applied the model system to investigate the distribution of Foxp3(+) regulatory T cells with Ki-67(+) proliferating cells within mouse tissue sections. The matrix model provides a tool to describe the expected distribution of two different cell types and their cell-cell-contacts within tissues. Comparing the degree of expected random distribution with experimental data might help to propose functional cell-cell-interactions in tissue sections.

Asunto(s)

Algoritmos , Comunicación Celular/fisiología , Simulación por Computador , Citometría de Imagen/métodos , Programas Informáticos , Linfocitos T Reguladores/citología , Animales , Proliferación Celular , Colon/citología , Colon/inmunología , Colon/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Factores de Transcripción Forkhead/análisis , Factores de Transcripción Forkhead/metabolismo , Inmunofenotipificación/métodos , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Ratones , Ratones Endogámicos C57BL , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo

RESUMEN

Hyaluronate (HA) was administered by intra-articular injection to a 13-year-old Haflinger mare for treatment of metacarpophalangeal osteoarthritis. Ten hours after the injection, a severe inflammatory reaction developed in the treated joint. While awaiting results of synovial fluid analysis, treatment for iatrogenic infectious arthritis was initiated, but the analysis did not confirm sepsis. Clinical signs improved significantly following systemic non-steroidal anti-inflammatory medication and the horse was discharged three days later. Following an intravenous hyaluronate injection, four days after discharge, the synovitis recurred. Synovial fluid analysis did not show any abnormalities, but the clinical signs were severe. The severe acute inflammatory reaction required systemic non-steroidal anti-inflammatory and intra-articular corticosteroid treatment in order to resolve the problem.

Asunto(s)

Adyuvantes Inmunológicos/efectos adversos , Enfermedades de los Caballos/diagnóstico , Ácido Hialurónico/efectos adversos , Articulación Metacarpofalángica , Osteoartritis/veterinaria , Sinovitis/veterinaria , Adyuvantes Inmunológicos/administración & dosificación , Animales , Diagnóstico Diferencial , Femenino , Caballos , Ácido Hialurónico/administración & dosificación , Inyecciones Intraarticulares/veterinaria , Osteoartritis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Sinovitis/inducido químicamente , Sinovitis/diagnóstico , Sinovitis/patología

RESUMEN

UNLABELLED: Whereas in adults angiodysplasia is a frequent cause of gastrointestinal bleeding, in children this disorder is extremely rare. A 7 10/12 year old girl is presented suffering over 3-4 months from mild but recurrent rectal bleeding. Blood count and serum ferritin and transferrin levels were normal. The rectosigmoideoscopy revealed a rectal lesion, which was confirmed histologically as angiodysplasia. Pathological investigation of the biopsies included HE staining and immunohistological staining of endothelial cells with anti-CD34 and anti-von Willebrand factor. A follow-up period of three years revealed spontaneous regression of the angiodysplastic lesion at the rectosigmoideal localisation, which could be confirmed by endoscopy. CONCLUSION: The outcome of the few pediatric patients described in the literature was reviewed. Due to the lack of conclusive understanding of the nature of this extremely rare vascular disorder and the variable outcome described, a wait and see attitude should be assumed in cases of less clinical affection.

Asunto(s)

Angiodisplasia/diagnóstico , Hemorragia Gastrointestinal/etiología , Angiodisplasia/complicaciones , Angiodisplasia/patología , Biopsia , Niño , Femenino , Estudios de Seguimiento , Hemorragia Gastrointestinal/patología , Humanos , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/patología , Proctoscopía , Recto/irrigación sanguínea , Recto/patología , Recurrencia , Remisión Espontánea

RESUMEN

BACKGROUND: The pathohistological features of Helicobacter pylori-associated gastritis in children and adolescents are less well understood than they are in adults. The aim of the study was to compare histological parameters of H. pylori-infected children with those of adults. METHODS: The retrospective study compared histological features of 111 children (mean age 10.8 +/- 3.8). Three paediatric age groups were analysed and the findings were compared with those of 111 adults (mean age 64.2 +/- 12.1). Degree of chronicity and activity of inflammation, mucus depletion and regeneration of foveolar epithelium by regenerating epithelium and H. pylori colonization were scored in antral biopsies. RESULTS: The histological parameters in children, i.e. degree of chronicity, activity of gastritis and the summed gastritis score, were not significantly different compared to those in adults. Replacement of foveolar epithelium by regenerating epithelium was significantly larger in adults compared to that of paediatric patients. The rate of low-grade mucus depletion and of the strongest degree of H. pylori colonization was higher in children than in adults. Children with antral nodularity had significantly higher histological score values. CONCLUSION: The histological differences between paediatric patients and adults are focused on signs of chronic inflammation and regeneration. Our results imply that antral nodularity is an important sign of highest-grade gastritis, especially in young children.

Asunto(s)

Gastritis/patología , Infecciones por Helicobacter/patología , Helicobacter pylori , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/microbiología , Gastroscopía , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad

RESUMEN

BACKGROUND: Mice with a targeted mutation in the G protein subunit G alpha i2 gene develop a colonic mucosal inflammation, with a highly activated B-cell response. We wanted to investigate whether this increased B-cell activity was directed against dietary antigens and/or various self tissues. METHODS: The level of antibodies specific for dietary (gliadin, soya and fish meal) antigens was measured by ELISA. Reactivity against self antigens was measured by immunohistochemistry on cryo-sectioned mouse and rat tissue. Sera and intestinal lavages were analysed from G alpha i2-/- mice before and after development of colitis and in age-matched wild type litter mates. RESULTS: Titres of antibodies against dietary antigens were significantly enhanced both in serum and in large intestinal lavages from G alpha i2-/- mice with ongoing colitis but not prior to disease, as compared to wild type mice. The autoreactivity to self tissues was significantly increased in G alpha i2-/- mice both before and after development of colitis as compared to litter mate control animals. Self tissue reactivity was directed not only against epithelial cells of the colon, small intestine and gastric glands, but also against smooth muscle cells, hepatocytes, bile duct cells, renal tubule and collecting tubule cells of the kidney. In analogy to human ulcerative colitis, autoantibodies against epithelial cells, bile duct epithelium and neutrophil granulocytes were found. CONCLUSIONS: Earlier increase in levels of autoantibodies (before onset of colitis) than of food antibodies (after onset of colitis) suggests the latter response to be a secondary phenomenon to e.g. a destroyed barrier function.

Asunto(s)

Autoanticuerpos/metabolismo , Linfocitos B/inmunología , Colitis/etiología , Proteínas en la Dieta/efectos adversos , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/deficiencia , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/inmunología , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/inmunología , Animales , Autoanticuerpos/sangre , Colitis/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Subunidad alfa de la Proteína de Unión al GTP Gi2 , Humanos , Mucosa Intestinal/inmunología , Ratones , Ratones SCID , Ratas , Ratas Sprague-Dawley

RESUMEN

OBJECTIVE: To test whether Helicobacter pylori-positive children are smaller and weigh less than H pylori-negative children. DESIGN: Cross-sectional population-based study. PARTICIPANTS: In 3,315 5-to 7-year-old preschool and school children, the putative influence of H pylori infection on growth was investigated. Standing height and weight were analyzed in relation to H pylori infection. The diagnosis of H pylori infection was established by 13C-urea-breath test. RESULTS: The prevalence of H pylori infection in boys was 7.2% (95% confidence interval, 5.9-8.9; n = 1,550) and in girls was 6.1% (95% confidence interval, 4.9-7.3; n = 1,552) H pylori-positive children were smaller than noninfected children (117.6 +/- 5.5 cm vs. 118.9 +/- 5.7 cm; P < 0.01). Although H pylori-positive boys were 2.06 cm smaller than H pylori-negative boys (117.4 +/- 5.6 cm vs. 119.5 +/- 5.7 cm; P < 0.001), the difference in girls was not significant (117.9 +/- 5.3 cm vs. 118.4 +/- 5.7 cm). When standing height was adjusted for age, the found differences were more pronounced. Differences between the infected and noninfected children with regard to body weight were not significant (22.4 +/- 4.0 kg vs. 22.1 +/- 4.0 kg), nor was there a significant difference with regard to body-mass index. However, boys with H pylori infection had a lower weight than noninfected boys (21.6 +/- 3.3 kg vs. 22.6 +/- 4.0 kg; P < 0.01), but in girls, these differences were not observed (22.2 +/- 4.0 vs. 22.8 +/- 4.6 kg, respectively). When weight was adjusted for age, H pylori -positive children also had a lower weight than H pylori -negative children because of the lower weight of boys. CONCLUSIONS: H pylori infection is associated with growth delay, growth retardation, or both in affected children.

Asunto(s)

Trastornos del Crecimiento/microbiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Estatura , Índice de Masa Corporal , Peso Corporal , Pruebas Respiratorias , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Alemania/epidemiología , Crecimiento , Humanos , Masculino , Prevalencia , Caracteres Sexuales

RESUMEN

OBJECTIVES: Antibodies that detect coeliac-toxic prolamins from wheat, barley and rye are important tools for controlling the diet of coeliac disease patients. Recently, a monoclonal antibody R5 that recognizes wheat gliadin, barley hordein and rye secalin equally was described. In this study, the epitope recognized by R5 was investigated. METHODS: Both a phage-displayed heptapeptide library and overlapping peptides spanning the sequence of alpha- and gamma-type gliadins (pepscan) were screened for binding of R5. RESULTS: Both techniques yielded comparable pentapeptide consensus sequences (phage display QXPW/FP; pepscan QQPFP). According to recent observations, this peptide stretch may be of key importance in the pathogenicity of coeliac disease. This sequence occurs repetitively in prolamins (in gamma- and omega-type prolamins more frequently than in alpha-type prolamins) together with several homologous peptide stretches, which are recognized less strongly. CONCLUSIONS: R5 seems to be a good candidate for the specific detection of putative coeliac disease-active sequences in prolamins and thus represents a valuable tool for the quality control of gluten-free food.

Asunto(s)

Anticuerpos Monoclonales/metabolismo , Enfermedad Celíaca/genética , Epítopos/genética , Gliadina/genética , Secuencia de Aminoácidos , Enfermedad Celíaca/inmunología , Ensayo de Inmunoadsorción Enzimática , Epítopos/inmunología , Análisis de los Alimentos , Gliadina/inmunología , Glútenes/genética , Humanos , Datos de Secuencia Molecular

RESUMEN

Screening a human small intestinal library with human serum yielded a clone which encoded a protein res4-22 the gene of which was highly homologous to a recently described gene located in the Huntington's disease locus. Autoantibodies against res4-22 (anti-res4-22), mainly of the immunoglobulin (Ig)A type, were detected in patients with neurological disorders at a higher frequency (18.4%) than in healthy blood donors (8.0%). In neurological patients with cerebral ischaemia anti-res4-22 was found significantly more often (47.4%) than in the total group of neurological patients. Anti-res4-22 positive sera showed significantly more frequently myelin staining in cerebellum and nerve sections than anti-res4-22 negative sera. Our findings demonstrate a new species of human autoantibodies against a newly described protein the function of which is still unknown.

Asunto(s)

Autoanticuerpos/inmunología , Autoantígenos/inmunología , Cromosomas Humanos Par 4/genética , Inmunoglobulina A/inmunología , Proteínas del Tejido Nervioso/inmunología , Enfermedades del Sistema Nervioso/inmunología , Autoanticuerpos/sangre , Autoantígenos/genética , Enfermedades Autoinmunes del Sistema Nervioso/sangre , Enfermedades Autoinmunes del Sistema Nervioso/genética , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Isquemia Encefálica/sangre , Isquemia Encefálica/inmunología , Cerebelo/inmunología , Biblioteca de Genes , Genes , Humanos , Proteína Huntingtina , Mucosa Intestinal/química , Intestino Delgado/química , Microscopía Fluorescente , Músculo Liso/química , Vaina de Mielina/inmunología , Proteínas del Tejido Nervioso/genética , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/genética , Proteínas Nucleares/genética , Proteínas , Células de Schwann/química , Homología de Secuencia de Ácido Nucleico

RESUMEN

BACKGROUND: The pathogenesis of coeliac disease (CD) and of dermatitis herpetiformis (DH) is strongly associated with production of autoantibodies, defined by indirect immunohistology. Recently, tissue transglutaminase (tTG) was identified as a prominent autoantigen. It would be important to investigate if further molecules apart from tTG are involved in autoimmunity. METHODS: Tissue sections of human foetal intestine were used to compare the distribution of tTG with the autoantibody binding patterns of 14 sera samples from patients with CD or DH. Double label experiments were performed using monoclonal as well as polyclonal tTG antibodies (anti-tTG) and patient sera. The staining was investigated by using conventional light and confocal laser scanning microscopy. RESULTS: Most autoantibody binding sites were matched by tTG. Further, the binding of autoantibodies could be inhibited by preincubation with monoclonal anti-tTG. However, in nine serum samples (64%) autoantibody staining suggested a few distinct binding sites apart from tTG. In three sera (21 %) autoantibody binding fibres were detected which definitely did not match monoclonal anti-tTG signals. Distinctly stained fibres were confirmed by applying polyclonal anti-tTG. This indicates the existence of autoantigenic epitopes not related to tTG.

Asunto(s)

Autoanticuerpos/metabolismo , Enfermedad Celíaca/inmunología , Dermatitis Herpetiforme/inmunología , Gliadina/inmunología , Intestinos/inmunología , Transglutaminasas/inmunología , Animales , Anticuerpos Monoclonales , Autoantígenos/inmunología , Autoantígenos/metabolismo , Sitios de Unión , Cobayas , Humanos , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Yeyuno/inmunología , Microscopía de Sonda de Barrido , Conejos , Transglutaminasas/metabolismo

RESUMEN

A phage displayed dodecapeptide library and synthetic octapeptides spanning the complete sequence of alpha- and gamma-type gliadin and overlapping in six amino acids (pepscan) were screened for binding to human gliadin antibodies (AGA). Phage display experiments led to four sequences recognized with significantly higher frequency by sera with raised IgA-AGA titres than by control sera. All these peptides contained the core sequence PEQ. Pepscan experiments revealed binding of AGA to five prominent regions: (i) QXQPFP (binding to IgG and IgA, X representing P, Q, and L); (ii) IPEQ (IgG) and WQIPEQ (IgA); (iii) FFQP (IgG) and QGXFQP (IgA, X representing F and S); (iv) PQQLPQ (IgG and IgA), all in alpha-type gliadin; and (v) QPQQPF (IgG and IgA) in gamma-type gliadin. In two of the sequences (QPQQPF and QQQPFP), substitution of Q by E resulting in QPEQPF and QEQPFP, respectively, increased significantly binding of AGA from sera of patients with biopsy-proven or suspected coeliac disease (CoD), all positive for endomysium antibodies (EmA). In contrast, binding of sera with high AGA titre from EmA-negative patients (CoD and dermatitis herpetiformis excluded) was not enhanced by this substitution. Thus, AGA directed against these modified epitopes can be regarded as specific for CoD. This is the first study demonstrating that deamidation of gliadin improves reactivity of AGA of CoD patients.

Asunto(s)

Linfocitos B/inmunología , Enfermedad Celíaca/inmunología , Epítopos/inmunología , Gliadina/inmunología , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Datos de Secuencia Molecular , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/inmunología , Biblioteca de Péptidos , Alineación de Secuencia

Asunto(s)

Fístula Biliar/tratamiento farmacológico , Colangiopancreatografia Retrógrada Endoscópica , Doxiciclina/administración & dosificación , Hepatectomía , Complicaciones Posoperatorias/tratamiento farmacológico , Humanos , Instilación de Medicamentos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

BACKGROUND AND OBJECTIVE: The significance of zinc in the pathogenesis of different dermatological conditions is controversial. Using our own patient collective, the present study aimed to determine variations in serum zinc levels in patients with atopic dermatitis and psoriasis as compared to levels in the normal population. PATIENTS/METHODS: The serum zinc levels of 97 patients with atopic dermatitis and 88 patients with psoriasis were compared to those in 22 healthy subjects and subjected to statistical analysis. RESULTS: In contrast to the data given in the literature, no statistically significant difference was found between the populations investigated. CONCLUSIONS: Zinc replacement therapy in patients with atopic dermatitis and psoriasis appears to be indicated only in those with a documented zinc deficiency.

Asunto(s)

Dermatitis Atópica/sangre , Psoriasis/sangre , Zinc/sangre , Adulto , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia

RESUMEN

A random phage heptapeptide library was screened with rabbit antibodies against wheat flour proteins comprising gliadins and a small amount of low molecular weight glutenins (gli/glu). Gli/glu antibodies isolated from the sera selected different consensus sequences (CS). All CS contained tri- to pentapeptide stretches homologous to gli/glu sequences (proposed epitopes). In alpha- and gamma-type gliadins, these sequences are clustered in the N-terminal region recently suspected to be toxic for humans with celiac disease. Peptides with CS were synthesized and checked for reactivity. Only immune and no control rabbit sera reacted with synthetic peptides. One of eight human sera containing gliadin antibodies was reactive as well (4/8 peptides) but control sera were negative. Thus the phage display technique is useful for epitope screening of polyclonal antibodies even in the case of a group of homologous but diverse antigens.

Asunto(s)

Anticuerpos/inmunología , Bacteriófagos , Epítopos/análisis , Gliadina/inmunología , Secuencia de Aminoácidos , Animales , Secuencia de Consenso , Ensayo de Inmunoadsorción Enzimática , Epítopos/química , Gliadina/química , Gliadina/genética , Haplorrinos , Humanos , Immunoblotting , Peso Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Biblioteca de Péptidos , Conejos

RESUMEN

On different tissue sections, binding of gliadin to reticular matrix components was observed which was Ca2+-dependent, inhibited by Cu2+ and Zn2+ ions, by putrescine, and by preincubation with antibodies against tissue transglutaminase (tTG) suggesting that binding of gliadin is mediated by tTG. tTG was able to bind to gliadin and fibronectin fixed to microplates. Furthermore, tTG mediated binding of gliadin to fibronectin coated to microplates. On tissue sections, treatment with sera containing coeliac disease autoantibodies yielded staining patterns very similar to that of bound gliadin. Dual label experiments by means of conventional and laser scanning microscopy revealed that most of autoantibody binding sites are matched by bound gliadin. However, lack of competition between gliadin and autoantibody binding hints to ligands in very close vicinity of this enzyme. Furthermore, there were several autoantibody binding regions which did not bind gliadin. This implies the existence of further autoantigenic epitopes not related to tTG.

Asunto(s)

Autoanticuerpos/inmunología , Enfermedad Celíaca/inmunología , GTP Fosfohidrolasas/inmunología , Proteínas de Unión al GTP , Gliadina/inmunología , Transglutaminasas/inmunología , Animales , Matriz Extracelular/inmunología , Humanos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Conejos , Ratas , Reticulum/inmunología

RESUMEN

To delineate the development of melatonin (MLT) production during childhood, we measured the excretion of MLT and 6-hydroxymelatonin sulfate (MLTS) in the urine of children (n = 134) from the 26th week of gestation until the age of 20 years. MLTS excretion showed a diphasic pattern with declining values in preterm babies with lowest values around term. After birth, the values remained low for the first 6 months of life. The highest values were reached between 4 and 7 years of age with a smooth but steady decline thereafter. A night-day difference was not detectable before the age of 6 months; the greatest night-day variations occurred at the time of the highest MLTS excretions. The MLT values showed an identical pattern but with amounts 1,000 times smaller; the ratio of MLTS to MLT increased from 40:1 in preterm babies to 900:1 in prepubertal children. In summary, the MLT/MLTS excretion exhibits the highest activity with respect to total secretory capacities as well as night-day differences at the time of gonadal quiescence during childhood. The strong inverse correlation of MLT and MLTS excretion with the hypothalamic-pituitary-gonadal activity points to a causal relationship between pineal gland activity and pubertal development.

Asunto(s)

Gónadas/crecimiento & desarrollo , Recién Nacido/orina , Recien Nacido Prematuro/orina , Melatonina/análogos & derivados , Melatonina/orina , Adolescente , Adulto , Niño , Preescolar , Ritmo Circadiano , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Lactante , Masculino , Glándula Pineal/fisiología , Pubertad/fisiología , Pubertad/orina

RESUMEN

Severe colitis, eventually complicated by toxic megacolon, perforation or massive hemorrhage still represents a potentially life threatening complication during the course of inflammatory bowel disease reaching a mortality of almost 40% if not operated in time. From 1.1.1973 until 30.4.1994 22 patients (13 men, 9 women, mean age 29 years) with either ulcerative colitis or Crohn's disease of the colon were operated on for severe colitis. Indications for operative treatment were as follows: 7 patients relapsed conservative medical treatment, 8 developed toxic megacolon and in 7 patients perforation occurred. Diagnosis was based on the clinical criterias first described by Turnbull. In 11 (50%) cases subtotal colectomy with an ileostomy and intrapelvic Hartmann's pouch was performed, in 4 (18%) patients a Turnbull's procedure was carried out with loop ileostomy and colostomies and in 3 (14%) cases a left hemicolectomy and transversostomy was applied. In two patients with Crohn's disease an ileocolic resection was done because of perforation, one received a subtotal colectomy and ileorectal anastomosis and one patient was operated by a right hemicolectomy and ileostomy. One patient with ulcerative colitis died, reaching a post-operative mortality of 4.5%. After an intervall of approximately 18 months in the 16 surviving patients with ulcerative colitis an ileal pouch-anal procedure could be done. Of the 5 patients with Crohn's disease one had to be operated on for recurrence, the other patients have been free of recurrent Crohn's disease for a follow-up time between 3 and 11 years. We conclude, provided early operative treatment is intended, that subtotal colectomy with Hartmann's pouch and ileostomy is the procedure of choice in patients with severe colitis.

Asunto(s)

Colitis Ulcerosa/cirugía , Enfermedad de Crohn/cirugía , Adulto , Colectomía , Enfermedades del Colon/cirugía , Femenino , Estudios de Seguimiento , Humanos , Ileostomía , Perforación Intestinal/cirugía , Masculino , Megacolon Tóxico/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Reoperación , Resultado del Tratamiento