RESUMEN
In 1999, based on a single family, spondyloepimetaphyseal dysplasia (SEMD) with mental retardation (MR) was described as a novel syndrome with probably X-linked recessive inheritance and unknown molecular defect (MIM 300232). Our purpose was to search for the causative defect in the originally described family and in an independently ascertained second family. All patients had slowly progressive neurodegeneration with central and peripheral involvement and identical skeletal dysplasia. Whole exome sequencing performed in two subjects showed a single plausible candidate - the p.Asp237Gly variant in AIFM1 (chr. Xq26.1). The p.Asp237Gly segregated with disease as indicated by linkage analysis [maximum logarithm of odds score (LOD) score at theta 0 for the two families was 3.359]. This variant had not been previously reported and it was predicted to be pathogenic by Polyphen2, SIFT, MutationTaster and Mutation Assessor. AIFM1 encodes mitochondria associated apoptosis-inducing factor. The AIFM1 gene has been linked with COXPD6 encephalomyopathy (MIM 300816), Cowchock syndrome (MIM 310490) and X-linked deafness with neuropathy (DFNX5, MIM 300614), none of which are similar to SEMD-MR. Our results place SEMD as the third instance of a skeletal phenotype associated with a mitochondrial disease (the others being EVEN-PLUS syndrome caused by mutations of HSPA9 and CODAS syndrome due to LONP1 mutations).
Asunto(s)
Factor Inductor de la Apoptosis/genética , Predisposición Genética a la Enfermedad/genética , Enfermedades Mitocondriales/genética , Mutación , Enfermedades Neurodegenerativas/genética , Osteocondrodisplasias/genética , Secuencia de Aminoácidos , Secuencia de Bases , Exoma/genética , Salud de la Familia , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Masculino , Enfermedades Mitocondriales/diagnóstico , Enfermedades Neurodegenerativas/diagnóstico , Osteocondrodisplasias/diagnóstico , Linaje , Fenotipo , Análisis de Secuencia de ADN/métodos , Homología de Secuencia de Aminoácido , SíndromeRESUMEN
We report two patients with Robinow syndrome, review the published literature and stress the importance and limitations of radiographic examination in the diagnosis of this disorder, which shows extreme clinical and radiographic variability. The radiographic differential diagnosis of Robinow syndrome is discussed.
Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Niño , Anomalías Craneofaciales/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Deformidades Congénitas de las Extremidades/diagnóstico por imagen , Radiografía , Columna Vertebral/anomalías , SíndromeRESUMEN
The use of magnetic resonance imaging as a readout method for polymer gel dosimetry commonly involves long imaging sessions, particularly when high spatial resolution is required in all three dimensions, for the investigation of dose distributions with steep dose gradients and stringent dose delivery specifications. In this work, a volume selective turbo spin echo (TSE) pulse sequence is compared to the established Carr-Purcell-Meiboom-Gill (CPMG) multiecho acquisition with regard to providing accurate dosimetric results in significantly reduced imaging times. Polyethylene glycol diacrylate based (PABIG) gels were irradiated and subsequently scanned to obtain R2 relaxation rate measurements, using a CPMG multiecho sequence and a dual echo TSE utilizing an acceleration (turbo) factor of 64. R2 values, plotted against corresponding Monte Carlo dose calculations, provided calibration data of PABIG gels dose response over a wide dose range. A linear R2 versus dose relationship was demonstrated for both sequences with TSE results presenting reduced dose sensitivity. Although TSE data were found to deviate from linearity at lower doses compared to CPMG data, a relatively wide dynamic dose range of response extending up to approximately 100 Gy was observed for both sequences. The TSE and CPMG sequences were evaluated with a brachytherapy irradiation using a high dose rate 192Ir source and a gamma knife stereotactic radiosurgery irradiation with a single 4 mm collimator helmet shot. Dosimetric results obtained with the TSE and CPMG are shown to compare equally well with the expected dose distributions for these irradiations. The 60-fold scan time reduction achieved with TSE implies that this sequence could prove to be a useful tool for the introduction of polymer gel dosimetry in clinical radiation therapy applications involving high doses and steep dose gradients.
Asunto(s)
Braquiterapia/métodos , Geles/química , Espectroscopía de Resonancia Magnética/métodos , Radiometría/métodos , Calibración , Relación Dosis-Respuesta en la Radiación , Estudios de Evaluación como Asunto , Radioisótopos de Iridio , Imagen por Resonancia Magnética/métodos , Método de Montecarlo , Fantasmas de Imagen , Polietilenglicoles/química , Polímeros/química , Dosis de Radiación , Radiocirugia/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Factores de TiempoRESUMEN
Spondyloepipmetaphyseal dysplasias (SEMDS) are characterized by flattening of the vertebral bodies and epi-metaphyseal involvement of all the tubular bones. We report a 13 year-old boy with a novel variant of SEMD that presents with rhizomelic/mesomelic shortening of the extremities and normal head, hands and feet. Variable metaphyseal involvement and relatively large proximal humeral and knee epiphyses are further distinctive radiographic features in this patient.
Asunto(s)
Huesos/anomalías , Osteocondrodisplasias/diagnóstico por imagen , Adolescente , Humanos , Masculino , Osteocondrodisplasias/clasificación , RadiografíaRESUMEN
We report here on a correlation between proton magnetic resonance spectroscopy (MRS) spectra obtained in children with posterior fossa tumors and tumor histology and grading. Twenty-six children (age 1-16) were investigated before surgery by using single-voxel proton MRS. All examination were performed on a 1.5 T MR scanner by using single-voxel (8 cm3) with PRESS sequence (TR 1600 ms, TE 270 ms, NEX 256). Spectra of N-acetylaspartate (NAA), choline containing compounds (Cho), creatine and phosphocreatine (Cr) and lactate (Lac) were evaluated. Absolute concentrations of the metabolites were measured and their ratios were calculated. Correlation between these and tumor histology and grading were then determined. Concentration of Cho and Lac, and Cho/NAA ratio were the major statistically significant parameters for discrimination between benign (WHO grade I and II) and malignant tumors (WHO grade III and IV), in particular between pilocytic astrocytomas and medulloblastomas. Discrimination between individual histological types within malignant and benign tumor groups was not possible. Proton MRS of pediatric posterior fossa tumors seems to be helpful in prediction of tumor grading and histology. Specific character of the examination requires establishing of the individual standards for every MR scanner.
Asunto(s)
Ácido Aspártico/análogos & derivados , Neoplasias Infratentoriales/metabolismo , Neoplasias Infratentoriales/patología , Espectroscopía de Resonancia Magnética , Adolescente , Ácido Aspártico/metabolismo , Astrocitoma/metabolismo , Astrocitoma/patología , Astrocitoma/cirugía , Niño , Preescolar , Colina/metabolismo , Creatina/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Neoplasias Infratentoriales/cirugía , Ácido Láctico/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Masculino , Meduloblastoma/metabolismo , Meduloblastoma/patología , Meduloblastoma/cirugía , Fosfocreatina/metabolismo , Protones , Índice de Severidad de la EnfermedadRESUMEN
The cases of two sisters with severe diastrophic dysplasia who showed some unusual radiographic features (kyphosis secondary to hypoplasia/dysplasia of the lumbar spine and a 'monkey wrench' appearance of the proximal femur) are reported here. Absent patellae were another feature that has not previously been reported in diastrophic dysplasia.
Asunto(s)
Fémur/diagnóstico por imagen , Cifosis/diagnóstico por imagen , Osteocondrodisplasias/diagnóstico por imagen , Pie Equinovaro , Enanismo , Femenino , Fémur/anomalías , Humanos , Lactante , Rótula/anomalías , RadiografíaRESUMEN
The pattern of alternating dense and lucent bands, with straight outer edges, at the youngest metaphysis of long bones, the "Afghan turban" sign, occurs when incompletely treated rickets has recurred and been retreated. Recognition of this, and other, rickets patterns allows the radiologist to influence treatment, as described in a very low birth weight infant.
Asunto(s)
Recien Nacido Prematuro , Raquitismo/diagnóstico por imagen , Clavícula/diagnóstico por imagen , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/etiología , Fémur/diagnóstico por imagen , Fémur/lesiones , Fracturas Espontáneas/diagnóstico por imagen , Fracturas Espontáneas/etiología , Humanos , Húmero/diagnóstico por imagen , Recién Nacido , Masculino , Radiografía Torácica , Costillas/diagnóstico por imagen , Raquitismo/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
UNLABELLED: A new X-linked variant of spondylo-epimetaphyseal dysplasia with distinctive phenotype and severe mental retardation in three boys of one family is reported. The children were normal at birth. After several months of normal development progressive physical disability and slow mental deterioration were observed. Extensive biochemical tests were normal. CONCLUSION: These patients represent a new form of X-linked spondylo-epimetaphyseal dysplasia.
Asunto(s)
Ligamiento Genético , Discapacidad Intelectual/genética , Osteocondrodisplasias/genética , Cromosoma X , Adolescente , Preescolar , Resultado Fatal , Humanos , Masculino , Osteocondrodisplasias/diagnóstico , Linaje , FenotipoRESUMEN
Two patients with a unique generalised bone dysplasia demonstrating severe distinctive platyspondyly are reported. This group of crippling disorders defies metabolic and histological classification. The radiographic examination is, at present, the only practical method of documentation of these rare disorders.
Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Huesos/anomalías , Enanismo/diagnóstico por imagen , Articulaciones/anomalías , Osteocondrodisplasias/diagnóstico por imagen , Anomalías Múltiples/genética , Adolescente , Artrografía , Huesos/diagnóstico por imagen , Niño , Enanismo/genética , Femenino , Humanos , Masculino , Osteocondrodisplasias/genética , FenotipoRESUMEN
A case is reported here of a boy with brachytelephalangic chondrodysplasia punctata. This is the first case of this disorder reported in the Australian literature.
Asunto(s)
Condrodisplasia Punctata/epidemiología , Cromosoma X , Australia/epidemiología , Condrodisplasia Punctata/diagnóstico por imagen , Condrodisplasia Punctata/genética , Ligamiento Genético , Humanos , Recién Nacido , Masculino , RadiografíaRESUMEN
A rare metabolic disease, alpha-mannosidosis, is described in two siblings. Psychomotoric deficiency, deafness, coarse face and radiological changes in the skeletal system indicated an inherited lysosomal storage disease.
Asunto(s)
alfa-Manosidosis/diagnóstico , Enfermedades Óseas/diagnóstico por imagen , Niño , Preescolar , Sordera , Femenino , Humanos , Masculino , Radiografía , alfa-Manosidosis/genéticaRESUMEN
Dominant symphalangism in three generations is presented in this paper. Conductive hearing loss of 14 year old male patient with proximal symphalangism was due to fixation of the stapes.
Asunto(s)
Deformidades de la Mano/complicaciones , Deformidades de la Mano/genética , Pérdida Auditiva Conductiva/complicaciones , Pérdida Auditiva Conductiva/diagnóstico , Adolescente , Audiometría de Tonos Puros , Deformidades de la Mano/diagnóstico , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
We have suggested previously that the histamine-diamine oxidase system is involved in cell proliferation. Therefore, the diamine oxidase activity and the histamine content were studied during mucosal proliferation induced by 70% resection of the small intestine of the rat with and without aminoguanidine (AG), a specific inhibitor of diamine oxidase (DAO). The DAO activity underwent a marked alteration during the period of mucosal proliferation, probably as an expression of an antiproliferative regulation mechanism. The histamine content decreased in the proliferating mucosa. No influence of AG on mucosal proliferation could be found, which might be due to a compensatory activity of the interconversion pathway.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/metabolismo , Histamina/metabolismo , Intestino Delgado/metabolismo , Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Animales , División Celular/efectos de los fármacos , Guanidinas/farmacología , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/cirugía , Intestino Delgado/citología , Intestino Delgado/cirugía , Masculino , Ratas , Ratas Endogámicas F344RESUMEN
The relationship between malignancy and histamine metabolism in the liver and the small intestine has been examined in sarcoma-bearing Wistar rats two weeks after subcutaneous implantation of a transplantable methylcholanthrene sarcoma Sa1828 and on the 3, 7 and 14th days after tumour extirpation. Two weeks after tumour implantation, the histamine level was increased by 100% and 50% in the liver and the small intestine, respectively. On the 3rd day after extirpation of the tumour the level of histamine had returned to the control values and remained unchanged during the next 10 days. Neither of the histamine catabolizing enzymes, diamine oxidase with a putrescine as a substrate or histamine methyltransferase were influenced by the existing tumour or by its extirpation except on the 14th day where a high increase in diamine oxidase activity was found. Some changes in the distribution of histamine metabolites suggest an involvement of an oxidative pathway of histamine catabolism as well as the aldehyde catabolizing enzymes in tumour development.
Asunto(s)
Histamina/metabolismo , Intestino Delgado/metabolismo , Hígado/metabolismo , Sarcoma Experimental/metabolismo , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Histamina N-Metiltransferasa/metabolismo , Trasplante de Neoplasias , Ratas , Ratas Endogámicas , Sarcoma Experimental/enzimologíaRESUMEN
The in vitro influence of ethanol and acetaldehyde on diamine oxidase catalyzed reaction was measured with guinea pig liver and intestine. Acetaldehyde, having no influence on diamine oxidase activity, diminished the formation of gamma-aminobutyric acid or imidazole-4-acetic acid when putrescine or histamine were used, respectively, as enzyme substrate. During ethanol ingestion by guinea pig the enhancement of hepatic diamine oxidase activity was observed after 10 days of treatment with subsequent decrease to the control value on the 18th day. The metabolic products of putrescine in diamine oxidase catalyzed reaction by livers of alcohol animals show similar increase and the same time course as enzymic activity. The per cent distribution of particular products in diamine oxidase reaction was not affected by ethanol administration.
Asunto(s)
Etanol/farmacología , Histamina/metabolismo , Hígado/metabolismo , Putrescina/metabolismo , Acetaldehído/farmacología , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Femenino , Cobayas , Imidazoles/metabolismo , Técnicas In Vitro , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Oxidación-Reducción , Ácido gamma-Aminobutírico/metabolismoRESUMEN
N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human intestinal diamine oxidase (ID50 = 1.6 X 10(-5) mol/l). This concentration corresponds to less than 5 g of wet weight of mushroom/l. The diamine oxidases from 5 other sources are inhibited in a similar manner. Semicarbazide and aminoguanidine are 10-respectively 1000-fold more potent inhibitors of the human intestinal diamine oxidase. An involvement of the diamine oxidase inhibitory property of N-methyl-N-formylhydrazine in toxic and mutagenic effects of the substance is considered.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Intestinos/enzimología , Metilhidrazinas/toxicidad , Monometilhidrazina/toxicidad , Mutágenos , Animales , Humanos , Mucosa Intestinal/efectos de los fármacos , Monometilhidrazina/análogos & derivados , Conejos , Ratas , Ratas Endogámicas , PorcinosRESUMEN
In adult hens diamine oxidase (histaminase) activity was found in gastrointestinal tract (with the highest value in ileum), liver and spleen. Intestinal diamine oxidase is predominantly a particle-bound enzyme. In the intestine oxidation of putrescine leads to delta 1-pyrroline formation, in liver both delta 1-pyrroline and gamma-aminobutyric acid are formed. The inhibitor properties of hen intestinal and rat intestinal diamine oxidases are very similar and differ from pea seedling diamine oxidase. The natural dipeptides carnosine and anserine are relatively potent inhibitors of hen intestinal diamine oxidase.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/análisis , Pollos/metabolismo , Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Animales , Hidrato de Cloral/farmacología , Femenino , Intestinos/enzimología , Hígado/metabolismo , Putrescina/metabolismo , Ratas , Ratas Endogámicas , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
High activities of diamine oxidase (EC 1.4.3.6) were measured in the intestinal tract of human subjects and of several mammalian species. The enzyme was localized in the mucosa and was distributed primarily in the cytoplasm; the only exception being the guinea-pig where it was located in the particulate fraction. Despite its instability the enzyme from human colonic mucosa was purified 80-fold. During the purification a soluble monoamine oxidase (EC 1.4.3.4) was separated from diamine oxidase. The pH optima of diamine oxidase for putrescine and histamine were 6.6-7.0 and 6.4-6.6, respectively. Short-chain aliphatic diamines were deaminated with the highest reaction velocity, but histamine and N tau-methylhistamine were also excellent substrates. The Km for putrescine was 8.3 x 10(-5) M, for histamine 1.9 x 10(-5) M and for N tau-methylhistamine 9.7 x 10(-5) M. Typical substrates of monoamine oxidase were not deaminated by the enzyme. Aminoguanidine strongly inhibited human intestinal diamine oxidase (IC50 = 1.1 x 10(-8) M). Because of its properties the intestinal diamine oxidase is considered to play a protective role against histamine in diseases such as ischaemic bowel syndrome, mesenteric infarction and ulcerative colitis.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/metabolismo , Histamina/metabolismo , Intestinos/enzimología , Adulto , Anciano , Animales , Fenómenos Químicos , Química , Perros , Femenino , Cobayas , Humanos , Mucosa Intestinal/enzimología , Cinética , Masculino , Ratones , Persona de Mediana Edad , Conejos , Ratas , Ratas Endogámicas , Especificidad de la Especie , Especificidad por Sustrato , PorcinosRESUMEN
Studies were performed on the distribution and properties of intestinal diamine oxidase (DAO) previously called histaminase. DAO activity is high in the gastrointestinal tract of all investigated species. The highest values are in the aboral part of the small intestine: where DAO is localized in the mucosa, predominantly in the top villus region. A high reaction velocity of human intestinal DAO is observed with putrescine, methylhistamine and histamine. H2 receptor antagonists and an agonist (impromidine) inhibit intestinal DAO. The physiological and pathophysiological significance of intestinal DAO in the regulation of histamine and putrescine levels is described, as is the possibility that DAO may act as a growth retardant.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/fisiología , Intestinos/enzimología , Amina Oxidasa (conteniendo Cobre)/deficiencia , Animales , Pollos , Perros , Femenino , Inhibidores de Crecimiento , Cobayas , Histamina/metabolismo , Humanos , Neoplasias Intestinales/etiología , Neoplasias Intestinales/prevención & control , Metilhistaminas/metabolismo , Ratones , Modelos Biológicos , Putrescina/metabolismo , Conejos , Ratas , Especificidad de la Especie , PorcinosRESUMEN
Imidazoles, aliphatic substrate analogues and the natural dipeptides, carnosine and anserine, were investigated as inhibitors of diamine oxidase from the pig kidney, human pregnancy plasma and pea seedlings. Imidazole, methylimidazoles, N-acetylimidazole, histamine and N tau-methylhistamine are relatively potent inhibitors of mammalian diamine oxidase showing no influence on plant enzymes. Anserine and carnosine are inhibitors of pig kidney and pea seedling enzymes. Ki values are 2 microM and 10 microM respectively. Investigated natural derivatives of putrescine and cadaverine have no influence on diamine oxidase of different origin. In conclusion, we present some evidence to suggest that mammalian diamine oxidase, despite a high reaction rate with putrescine, is better adapted to histamine oxidation, whereas for plant enzymes the diamines are preferred substrates.