Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To protect against reactive oxygen species, prokaryotic and eukaryotic cells have developed an antioxidant defence mechanism where O2- is converted to H2O2 by superoxide dismutase (Sod), and in a second step, H2O2 is converted to H2O by catalase (Cat) and/or glutathione peroxidase (Gpx). If Sod levels are increased without a concomitant Gpx increase, then the intermediate H2O2 accumulates. This intermediate could undergo the Fenton's reaction, generating hydroxyl radicals which may lead to lipid peroxidation in cells. In this study, we investigate the expression of Sod1, Gpx1 and susceptibility to lipid peroxidation during the aging process in mouse brains. We demonstrate that the mRNA levels and enzyme activity of Sod1 are higher in brains from adult mice compared to neonatal mice. Furthermore, we show that a linear increase in Sod1 mRNA and enzyme activity occurs with aging (1-100 weeks). On the contrary, we find that the mRNA and enzyme activity for Gpx1 does not increase with aging in mouse brains. In addition, our results demonstrate that the susceptibility of murine brains to lipid peroxidation increases with aging. The data in this study are consistent with the notion that reactive oxygen species may contribute to the aging process in mammalian brains. These results are discussed in relation to the normal aging process in mammals, and to the premature aging and mental retardation in Down syndrome.
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PMID:Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains. 159 44

Trisomy 21 (Down's syndrome, DS) is the most frequent chromosomal aberration. Triplication of a small region of chromosome 21, the fragment 21q22 is sufficient to cause the DS phenotype including immunodeficiency, premature aging, neurodegenerations, mental retardation and an increased risk of leukemia. Chromosomal aberrations caused by X-ray irradiation were observed in DS lymphocytes and DS fibroblasts, but the correlation to cell death or repair deficiency was not clear. We approached this problem and report here on a profound X-ray repair deficiency of DS cells. With a colorimetric viability assay we observed an UV sensitivity of DS fibroblasts at doses beyond 14 Jm-2 but no significant X-ray sensitivity. By the nucleoid sedimentation technique, a deficient restoration of nucleoids in DS cells after X-ray irradiation was demonstrated. The same features apply for cells, which contain an overexpressed Cu/Zn-superoxide dismutase (SOD-1) gene. Radiation sensitivity of DS cells and SOD-1 overexpressing cells resemble those of ataxia telangiectasia (AT) fibroblasts. Additionally, DS and AT cells exert lack of inhibition of DNA synthesis after X-ray irradiation.
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PMID:Radiation sensitivity of Down's syndrome fibroblasts might be due to overexpressed Cu/Zn-superoxide dismutase (EC 1.15.1.1). 252 18

Neuropathological findings in two patients with Cockayne's syndrome, a rare familial condition with mental retardation, progressive neurological deficits, progeria, and dwarfism, are described. Both patients showed extensive tigroid demyelination of the white matter and massive calcifications in the striatum, pallidum, and dentate nucleus. In one patient, neurofibrillary tangles were found in neurons in the nucleus basalis of Meynert, locus ceruleus, substantia nigra, and cerebral cortex, while in the other case only a few tangles were seen in the cerebral cortex. Electron microscopy revealed paired helical filaments. The presence of neurofibrillary tangles in Cockayne's syndrome, rarely reported previously, could suggest premature aging of the brain.
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PMID:Cockayne's syndrome: report of two autopsy cases associated with neurofibrillary tangles. 370 54

Aneuploid chromosomal disorders may offer insight into the pathogenesis of certain common diseases. The birth defects and mental retardation that characterize Down's syndrome are well recognized. In addition, the altered chromosomal content that occurs in the syndrome apparently affects the prevalence of a variety of disorders, such as malignancy, endocrine dysfunction, infection, atherosclerosis, and premature aging. Because the single distinguishing factor in Down's syndrome is the presence of an excess of a part of chromosome 21, the genetic information contained in this chromosomal segment seems to be responsible for the disease manifestations. Techniques of somatic cell genetics and molecular biology allow mapping of human genes and study of their expression. With such methods it should be possible to understand Down's syndrome and other aneuploid disorders and to apply these considerations to other areas of medicine.
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PMID:Down's syndrome as a model disease. 646 5

A 4-year-old female with Cockayne syndrome presented for cataract extraction under general anesthesia. She was thin and frail; her neck, epiglottis and larynx were stiff; she was deaf and blind; and she could not speak, sit unaided, or perspire. At the time of her admission, she weighed 5.5 kg. Cockayne syndrome is a disease of childhood characterized by mental retardation and premature aging. Although the underlying abnormality appears to be autosomal recessive inheritance or metabolic (possibly thymic) dysfunction, there is no consensus on etiology. The multiple organ involvement carries significant implications for the anesthetist. Intubation can be technically difficult, and care of the skin can be problematic. Essential hypertension, hepatic deficiencies, osteoporosis, deafness, blindness, and other effects of premature aging may be encountered making perioperative management a challenge.
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PMID:Cockayne syndrome: a case report. 781 Feb 87

A new group of recessively inherited metabolic disorders affecting glycoprotein metabolism has been identified--the carbohydrate-deficient-glycoprotein (CDG) syndromes. Here the course and clinical expression of CDG syndrome type I in 13 patients who have passed the age of 15 years are described. All presented with early onset psychomotor retardation, in most cases combined with slight facial dysmorphic features, some degree of hepatic dysfunction, and in one case, pericardial effusion. About half of the patients had subcutaneous lipodystrophy and comatose or stroke-like episodes during childhood. After the age of 15 the disease was mainly characterised by neurological symptoms consisting of non-progressive ataxia associated with cerebellar hypoplasia, stable mental retardation, variable peripheral neuropathy, and strabismus. One third of the patients had generalised seizures, usually sporadic, and all had retinal pigmentary degeneration. In all cases there was more or less pronounced thoracic deformity and no female had passed puberty. Also, the oldest female showed premature aging. Severe internal organ symptoms, which are common in pediatric patients, were absent. All patients had highly raised serum concentrations of the biochemical marker carbohydrate-deficient transferrin, which can be used to verify the diagnosis. It is concluded that after childhood, CDG syndrome type I is a largely non-progressive disease compatible with a socially functioning but dependent lifestyle.
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PMID:Carbohydrate-deficient glycoprotein syndrome: clinical expression in adults with a new metabolic disease. 820 22

In Down's syndrome (DS) mental retardation accompanying chromosomal abnormalities is seen, and the incidence of associated congenital heart abnormalities is also known to recent years, the accelerated aging and premature senility associated with DS have attracted attention. In the present study, we examined cardiac lesions using echocardiography in a group of asymptomatic adult DS subjects discussed the relation between these lesions and premature aging. The subjects comprised 28 adult DS patients ranging in age from 20 to 46 years (mean +/- SD, 30.8 +/- 8.9 years) residing in 8 institutions in Fukui prefecture. The presence of DS was confirmed in all cases by chromosomal examination, which revealed 21-trisomy in 25 and mosaic type in three. Of indices of left heart function, the end diastolic volume index (EDVI) and end systolic volume index (ESVI) showed significantly reduced values, whereas indices of systolic function such as the ejection fraction (EF) and mean velocity of circumferential fiber shortening (mean Vcf) showed significantly elevated values. The results of early diastolic left ventricular function, which has been noted to be related to aging, did not show any significant difference as determined by observation of mitral valve dynamics. On the other hand, morphologically, mitral valve prolapse (MVP) was found significantly more frequently in the DS group (17.9%) as compared to a normal control group. Also, valvular calcification (14.3%) and aortic valve regurgitation (AR, 11%) were both frequently noted. Whether signs such as valvular calcification are findings related to accelerated aging will require further study.
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PMID:[Echocardiographic study in adult patients with Down's syndrome]. 836 Oct 52

The human Cu/Zn superoxide dismutase (hSOD-1) gene, catalyses the dismutation of O2 to H2O2 and O2. It is located on chromosome 21 in q22.1 and is overexpressed in Down's syndrome (DS) patients. These patients present various abnormalities including mental retardation, congenital heart disease, immunological deficits and premature aging. In order to explore the potential role of SOD-1 overexpression in DS, we have generated two lineages of transgenic mice for the hSOD-1 gene and studied, at the ultrastructural level, the effect of hSOD-1 overexpression on the thymic microenvironment. Modification of the cellular architecture and morphology associated with a lipidic invasion, signs of a premature involution of the thymus, were observed in both lineages. A rupture of the filamentous network in the extracellular and probably also in the intracellular matrix was first observed. These results correlate the thymic alterations visualized in light microscopy, on the thymus from DS patients, and raise the question of the relationship between the SOD-1 overexpression and the different morphological alterations associated with the premature thymic involution observed in SOD-1 transgenic mice. They suggest that thymic and immunological impairments present in DS patients may be related to the SOD-1 gene dosage effect.
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PMID:Premature thymic involution, observed at the ultrastructural level, in two lineages of human-SOD-1 transgenic mice. 922 11

In Down's syndrome, the presence of three copies of chromosome 21 is associated with premature aging and progressive mental retardation sharing the pathological features of Alzheimer disease. Early cortical dysgenesis and late neuronal degeneration are probably caused by an overproduction of amyloid beta-peptide, followed by an increased cellular oxidation. Interestingly, chromosome 21 codes for superoxide-dismutase and amyloid beta precursor resulting, in Down's syndrome, in an overflow of these gene products and metabolites. We studied Down's fetal brain cortex to evaluate the presence and amount of lipid and protein oxidation markers; moreover, we quantified two forms of glycation end products that are known to be involved in the process of cellular oxidation. All these parameters are significantly increased in Down's fetal brains in comparison to controls, providing the evidence that accelerated brain glycoxidation occurs very early in the life of Down's syndrome subjects.
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PMID:Early glycoxidation damage in brains from Down's syndrome. 950 Oct 12

Wiedemann-Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome. The girl is now 16 years and 10 months old and has had follow-up from birth. We measured terminal restriction fragment (TRF) length to evaluate whether the patient's premature aging process is accompanied by shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb found in our patient's fibroblasts is not shortened as compared to that of normal fibroblasts. Our results differ from those observed in Hutchinson-Gilford progeria.
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PMID:Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal telomere length in skin fibroblasts. 1156 21


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