RESUMO
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).
Assuntos
Fator de Indução de Apoptose/genética , Predisposição Genética para Doença/genética , Doenças Mitocondriais/genética , Mutação , Doenças Neurodegenerativas/genética , Osteocondrodisplasias/genética , Sequência de Aminoácidos , Sequência de Bases , Exoma/genética , Saúde da Família , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Osteocondrodisplasias/diagnóstico , Linhagem , Fenótipo , Análise de Sequência de DNA/métodos , Homologia de Sequência de Aminoácidos , SíndromeRESUMO
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.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Criança , Anormalidades Craniofaciais/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Deformidades Congênitas dos Membros/diagnóstico por imagem , Radiografia , Coluna Vertebral/anormalidades , SíndromeRESUMO
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.
Assuntos
Braquiterapia/métodos , Géis/química , Espectroscopia de Ressonância Magnética/métodos , Radiometria/métodos , Calibragem , Relação Dose-Resposta à Radiação , Estudos de Avaliação como Assunto , Radioisótopos de Irídio , Imageamento por Ressonância Magnética/métodos , Método de Monte Carlo , Imagens de Fantasmas , Polietilenoglicóis/química , Polímeros/química , Doses de Radiação , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Fatores de TempoRESUMO
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.
Assuntos
Osso e Ossos/anormalidades , Osteocondrodisplasias/diagnóstico por imagem , Adolescente , Humanos , Masculino , Osteocondrodisplasias/classificação , RadiografiaRESUMO
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.
Assuntos
Ácido Aspártico/análogos & derivados , Neoplasias Infratentoriais/metabolismo , Neoplasias Infratentoriais/patologia , Espectroscopia de Ressonância Magnética , Adolescente , Ácido Aspártico/metabolismo , Astrocitoma/metabolismo , Astrocitoma/patologia , Astrocitoma/cirurgia , Criança , Pré-Escolar , Colina/metabolismo , Creatina/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Neoplasias Infratentoriais/cirurgia , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Masculino , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Meduloblastoma/cirurgia , Fosfocreatina/metabolismo , Prótons , Índice de Gravidade de DoençaRESUMO
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.
Assuntos
Fêmur/diagnóstico por imagem , Cifose/diagnóstico por imagem , Osteocondrodisplasias/diagnóstico por imagem , Pé Torto Equinovaro , Nanismo , Feminino , Fêmur/anormalidades , Humanos , Lactente , Patela/anormalidades , RadiografiaRESUMO
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.
Assuntos
Recém-Nascido Prematuro , Raquitismo/diagnóstico por imagem , Clavícula/diagnóstico por imagem , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Fêmur/diagnóstico por imagem , Fêmur/lesões , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Humanos , Úmero/diagnóstico por imagem , Recém-Nascido , Masculino , Radiografia Torácica , Costelas/diagnóstico por imagem , Raquitismo/complicações , Índice de Gravidade de DoençaRESUMO
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.
Assuntos
Ligação Genética , Deficiência Intelectual/genética , Osteocondrodisplasias/genética , Cromossomo X , Adolescente , Pré-Escolar , Evolução Fatal , Humanos , Masculino , Osteocondrodisplasias/diagnóstico , Linhagem , FenótipoRESUMO
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.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Osso e Ossos/anormalidades , Nanismo/diagnóstico por imagem , Articulações/anormalidades , Osteocondrodisplasias/diagnóstico por imagem , Anormalidades Múltiplas/genética , Adolescente , Artrografia , Osso e Ossos/diagnóstico por imagem , Criança , Nanismo/genética , Feminino , Humanos , Masculino , Osteocondrodisplasias/genética , FenótipoRESUMO
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.
Assuntos
Condrodisplasia Punctata/epidemiologia , Cromossomo X , Austrália/epidemiologia , Condrodisplasia Punctata/diagnóstico por imagem , Condrodisplasia Punctata/genética , Ligação Genética , Humanos , Recém-Nascido , Masculino , RadiografiaRESUMO
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.
Assuntos
alfa-Manosidose/diagnóstico , Doenças Ósseas/diagnóstico por imagem , Criança , Pré-Escolar , Surdez , Feminino , Humanos , Masculino , Radiografia , alfa-Manosidose/genéticaRESUMO
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.
Assuntos
Deformidades da Mão/complicações , Deformidades da Mão/genética , Perda Auditiva Condutiva/complicações , Perda Auditiva Condutiva/diagnóstico , Adolescente , Audiometria de Tons Puros , Deformidades da Mão/diagnóstico , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
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.
Assuntos
Amina Oxidase (contendo Cobre)/metabolismo , Histamina/metabolismo , Intestino Delgado/metabolismo , Amina Oxidase (contendo Cobre)/antagonistas & inibidores , Animais , Divisão Celular/efeitos dos fármacos , Guanidinas/farmacologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/cirurgia , Intestino Delgado/citologia , Intestino Delgado/cirurgia , Masculino , Ratos , Ratos Endogâmicos F344RESUMO
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.
Assuntos
Histamina/metabolismo , Intestino Delgado/metabolismo , Fígado/metabolismo , Sarcoma Experimental/metabolismo , Amina Oxidase (contendo Cobre)/metabolismo , Animais , Histamina N-Metiltransferase/metabolismo , Transplante de Neoplasias , Ratos , Ratos Endogâmicos , Sarcoma Experimental/enzimologiaRESUMO
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.
Assuntos
Etanol/farmacologia , Histamina/metabolismo , Fígado/metabolismo , Putrescina/metabolismo , Acetaldeído/farmacologia , Amina Oxidase (contendo Cobre)/metabolismo , Animais , Feminino , Cobaias , Imidazóis/metabolismo , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Oxirredução , Ácido gama-Aminobutírico/metabolismoRESUMO
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.
Assuntos
Amina Oxidase (contendo Cobre)/antagonistas & inibidores , Intestinos/enzimologia , Metilidrazinas/toxicidade , Monometilidrazina/toxicidade , Mutagênicos , Animais , Humanos , Mucosa Intestinal/efeitos dos fármacos , Monometilidrazina/análogos & derivados , Coelhos , Ratos , Ratos Endogâmicos , SuínosRESUMO
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.
Assuntos
Amina Oxidase (contendo Cobre)/análise , Galinhas/metabolismo , Amina Oxidase (contendo Cobre)/antagonistas & inibidores , Animais , Hidrato de Cloral/farmacologia , Feminino , Intestinos/enzimologia , Fígado/metabolismo , Putrescina/metabolismo , Ratos , Ratos Endogâmicos , Ácido gama-Aminobutírico/fisiologiaRESUMO
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.
Assuntos
Amina Oxidase (contendo Cobre)/metabolismo , Histamina/metabolismo , Intestinos/enzimologia , Adulto , Idoso , Animais , Fenômenos Químicos , Química , Cães , Feminino , Cobaias , Humanos , Mucosa Intestinal/enzimologia , Cinética , Masculino , Camundongos , Pessoa de Meia-Idade , Coelhos , Ratos , Ratos Endogâmicos , Especificidade da Espécie , Especificidade por Substrato , SuínosRESUMO
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.
Assuntos
Amina Oxidase (contendo Cobre)/fisiologia , Intestinos/enzimologia , Amina Oxidase (contendo Cobre)/deficiência , Animais , Galinhas , Cães , Feminino , Inibidores do Crescimento , Cobaias , Histamina/metabolismo , Humanos , Neoplasias Intestinais/etiologia , Neoplasias Intestinais/prevenção & controle , Metilistaminas/metabolismo , Camundongos , Modelos Biológicos , Putrescina/metabolismo , Coelhos , Ratos , Especificidade da Espécie , SuínosRESUMO
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.