Parkinson's disease and Alzheimer's disease: neurodegenerative disorders due to brain antioxidant system deficiency?
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Alzheimer Disease↗
Biomedical subjects
A Nicole
Publications and source records attributed to A Nicole.
Acute pulmonary oedema following administration of ornithine-8-vasopressin.
We report the case of a patient who developed acute pulmonary oedema following a short and uneventful surgical procedure. Among the differential diagnoses, the role of ornithine-8-vasopressin is emphasized.
Acute Disease↗
The hyperreactive malarial splenomegaly syndrome in a European: has the treatment a modulatory effect on the immune system?
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Chloroquine↗
Slot blot method for the quantification of DNA sequences and mapping of chromosome rearrangements: application to chromosome 21.
As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots using specific and reference probes, we designed a "slot blot" method for the evaluation of the copy number of unique chromosome 21 sequences. Varying amounts of denatured DNA from a normal control, a trisomy 21 patient, and the subject to be analyzed were loaded on the same membrane. Successive hybridizations with reference probes and chromosome 21 probes were then carried out. Intensities of the signals on autoradiograms were quantified by densitometric scanning. Graphic and statistical analysis of the linear regressions between reference and chromosome 21 probe signals were performed, and the conclusion that the DNA from the studied subject had two or three copies for a given chromosome 21 sequence was assessed by statistical comparison of the slopes. As a test for the validation of this method, 10 coded blood DNAs from five normal controls and from five trisomy 21 patients were analyzed, by using two reference (COL1A1 and COL1A2) and two chromosome 21 (D21S11 and D21S17) probes. Among the 10 DNAs analyzed, it was possible to diagnose, with 100% accuracy, normal controls and trisomic 21 individuals. Application of this methodology to the mapping of partial chromosome 21 rearrangements is presented.
Base Sequence↗
Critical role of the D21S55 region on chromosome 21 in the pathogenesis of Down syndrome.
The duplication of a specific region of chromosome 21 could be responsible for the main features of Down syndrome. To define and localize this region, we analyzed at the molecular level the DNA of two patients with partial duplication of chromosome 21. These patients belong to two groups of Down syndrome patients characterized by different partial trisomies 21: (i) duplication of the long arm, proximal to 21q22.2, and (ii) duplication of the end of the chromosome, distal to 21q22.2 We assessed the copy number of five chromosome 21 sequences (SOD1, D21S17, D21S55, ETS2, and D21S15) and found that D21S55 was duplicated in both cases. By means of pulsed-field gel analysis and with the knowledge of regional mapping of the probes D21S17, D21S55 and ETS2, we estimated the size of the common duplicated region to be between 400 and 3000 kilobases. This region, localized on the proximal part of 21q22.3, is suspected to contain genes the overexpression of which is crucial in the pathogenesis of Down syndrome.
Chromosome Banding↗
Preferential localization of copper zinc superoxide dismutase in the vulnerable cortical neurons in Alzheimer's disease.
The distribution of cells containing CuZn superoxide dismutase (CuZn SOD) was determined in hippocampi and associative cortex from normal and Alzheimer's individuals by using antisera against native and denatured CuZn SOD proteins. Immunostaining was intense in large pyramidal neurons, moderate in hippocampal granule cells and very weak in other cells. In the hippocampus of an Alzheimer's patient, successive immunostaining of the same tissue section by anti CuZn SOD and anti paired helical filaments antisera show that both normal and degenerating cells are labelled by the anti CuZn SOD antiserum. Thus, large pyramidal neurons which are potentially susceptible to degenerative processes in AD have the property to contain higher amounts of CuZn SOD than other brain cells.
Aged↗
Expression of transfected human CuZn superoxide dismutase gene in mouse L cells and NS20Y neuroblastoma cells induces enhancement of glutathione peroxidase activity.
The human CuZn superoxide dismutase (superoxide dismutase 1) a key enzyme in the metabolism of oxygen free-radicals, is encoded by a gene located on chromosome 21 in the region 21 q 22.1 known to be involved in Down's syndrome. A gene dosage effect for this enzyme has been reported in trisomy 21. To assess the biological consequences of superoxide dismutase 1 overproduction within cells, the human superoxide dismutase 1 gene and a human superoxide dismutase 1 cDNA were introduced into mouse L cells and NS20Y neuroblastoma cells. Both cell types expressed elevated levels (up to 3-fold) of enzymatically active human superoxide dismutase 1. These human superoxide dismutase 1 overproducers, especially neuronal cell lines, showed an increased activity in the selenodependent glutathione peroxidase. These data are consistent with the possibility that gene dosage of superoxide dismutase 1 contributes to oxygen metabolism modifications previously described in Down's syndrome.
Animals↗
X-linked lymphoproliferative syndrome. Identification of a large family in Switzerland.
Observation of a patient with acquired hypogammaglobulinemia associated with a mononucleosis syndrome led to the identification of one of the largest families affected by the X-linked lymphoproliferative (XLP) syndrome in the world. It is the first such family identified in Switzerland and the largest in Europe. At least nine male subjects over two generations presented phenotypic expressions consistent with the XLP syndrome. Study of the pedigree extending over seven generations suggests that the mutation occurred in the proband's great-grandmother. In the next generation, a second mutation of the X chromosome in one branch of the family resulted in expression of hemophilia A in the children. This remarkably large family, comprising six living obligate female carriers, displays a wide spectrum of the XLP syndrome and offers valuable information for future genetic linkage studies and for genetic counseling.
Adult↗
Twofold CuZnSOD activity suggesting homozygous submicroscopic duplication of chromosome 21 in the orangutan.
A twofold CuZnSOD activity was observed in an orangutan as compared to man and a chimpanzee. This suggests that a submicroscopic duplication of chromosome 21 (similar to those demonstrated in patients with the trisomy 21 phenotype but with a normal karyotype) has occurred in the homozygous state during evolution of the orangutan phylum. Such duplications could be important evolutionary mechanisms, together with visible chromosome rearrangements and classical gene mutations.
Animals↗
Cloning and sequencing of a rat CuZn superoxide dismutase cDNA. Correlation between CuZn superoxide dismutase mRNA level and enzyme activity in rat and mouse tissues.
The molecular cloning and nucleotide sequence of a cDNA clone (pR SOD) for rat CuZn superoxide dismutase (CuZnSOD) is reported. Nucleotide sequence homology with human superoxide dismutase is 86% for the coding region and 71% for the 3' untranslated region. The deduced amino acid sequence is given and the homologies with the sequences reported for other species are presented. Northern blot analysis of total RNA from various rat and mouse tissues and from two mouse cell lines show that pR SOD hybridizes with one mRNA species of about 0.7 kb. The amount of CuZnSOD mRNA in each tissue, measured by densitometry of the Northern blot autoradiograms, correlates with the enzymatic activity based on protein content. These results indicate that the control of CuZnSOD activity in mammalian tissues is largely dependent on the regulation of CuZnSOD mRNA levels. In human liver, fibroblasts and FG2 hepatoma cells, two CuZnSOD mRNAs (0.7 kb and 0.9 kb) are observed. The level of CuZnSOD mRNA in FG2 is 25% that of the liver and four times more abundant than in fibroblasts.
Amino Acid Sequence↗
Beta amyloid gene duplication in Alzheimer's disease and karyotypically normal Down syndrome.
With the recently cloned complementary DNA probe, lambda Am4 for the chromosome 21 gene encoding brain amyloid polypeptide (beta amyloid protein) of Alzheimer's disease, leukocyte DNA from three patients with sporadic Alzheimer's disease and two patients with karyotypically normal Down syndrome was found to contain three copies of this gene. Because a small region of chromosome 21 containing the ets-2 gene is duplicated in patients with Alzheimer's disease, as well as in karyotypically normal Down syndrome, duplication of a subsection of the critical segment of chromosome 21 that is duplicated in Down syndrome may be the genetic defect in Alzheimer's disease.
Adult↗
[The long QT syndrome: importance of phonocardiography and ergometry].
The chronological relationship between the S2 of the phonocardiogram and the T wave of the ECG, and the behaviour of the QT and QTc intervals, have been investigated in two cases of idiopathic long QT syndrome (LQTS) at rest and during effort. At rest and during effort with heart rates (HR) under 120/min, the S2 is always abnormal before the end of the T wave where the QTc interval is generally prolonged, but is sometimes within normal range (less than or equal to 440 msec). In cases where the QTc interval falls within normal range, the use of Bazett's formula to calculate the QTc interval may mislead and cause the existence of LQTS to be overlooked. Study of the chronological relationship (timing) between S2 and T wave is a reliable method of detecting LQTS even with a normal QTc interval. During ergometer exercise, if we observe (as in our two cases) not only a normal acceleration of the HR but a shortening and even a normalization of the QTc interval, therapeutic abstention (betablockers) may be recommended in asymptomatic LQTS. It is concluded that (1) in LQTS at rest and with HR under 120/min, S2 is always abnormal before the end of the T wave, (2) study of the timing S2/T wave is a reliable method of detecting the existence of LQTS even with a normal QTc interval, (3) in asymptomatic LQTS where the QTc interval shortens or falls within normal range during effort with S2 appearing at the end of the T wave, as reported in our first case, therapeutic abstention (betablockers) may be recommended.
Adolescent↗
Down syndrome with duplication of a region of chromosome 21 containing the CuZn superoxide dismutase gene without detectable karyotypic abnormality.
We report the case of an 18-month-old boy with many typical Down syndrome features but a normal cytogenetic analysis. High-resolution banding techniques on lymphocytes and fibroblasts of the propositus and his parents did not show any detectable abnormality including that of trisomy 21 mosaicism. However, CuZn superoxide dismutase (CuZn SOD) in the patient's red cells was increased as in trisomy 21. DNA analysis (Southern blots) using a human CuZn SOD probe showed that the genotype of the propositus contained three CuZn SOD genes. In situ hybridization on metaphase chromosomes with the same probe confirmed the gene location in a segment enclosing the distal part of 21q21 and 21q22.1. There was no significant labeling on other chromosomes of the patient. These results indicate that the Down syndrome phenotype of this patient is due to microduplication of a chromosome 21 fragment containing the CuZn SOD gene.
Chromosome Mapping↗
Submicroscopic duplication of chromosome 21 and trisomy 21 phenotype (Down syndrome).
A patient with the phenotype of trisomy 21 (Down syndrome) was found to have a normal karyotype in blood lymphocytes and fibroblasts. Assessment of the chromosome 21 markers SOD1, CBS, ETS2, D21S11, and BCEI showed partial trisomy by duplication of a chromosome segment carrying the SOD1, CBS, and ETS2 loci and flanked by the BCEI and D21S11 loci, which are not duplicated. This submicroscopic duplication at the interface of 21q21 and 21q22.1 reduces to about 2000-3000 kb the critical segment the trisomy of which is responsible for the phenotype of trisomy 21.
Adult↗
[Cholera in Fribourg. Apropos a case].
A 41-year-old man from Cameroon was admitted to the Hospital of Fribourg (Switzerland) for watery diarrhea 3 months after cholera vaccination. Stool cultures were positive for Vibrio cholerae, biotype El Tor. Treatment consisted of rehydration (up to 9 litres per day) and correction of metabolic acidosis. No antibiotics were administered. The diagnosis of cholera should be considered in the presence of watery diarrhea in travellers or immigrants from countries suffering from the pandemic, even though, before this case, there had been no registered case for four years in Switzerland and none for twenty years in Fribourg.
Adult↗
Rearrangement of chromosome 21 in Alzheimer's disease.
We have analyzed the DNA from four patients suffering from a dementia of the Alzheimer type and of four controls of identical age. Estimates of the copy numbers of two genes located on chromosome 21, SOD1 and ETS2, gave the following results: in all the cases there was duplication of ETS2 whereas SOD1 was normal. These preliminary results indicate that the segment of chromosome 21(q21----q22.1) is rearranged in all the four patients who were investigated.
Alzheimer Disease↗
Lowered level of translatable messenger RNAs for manganese superoxide dismutase in human fibroblasts transformed by SV 40.
The activity of manganese superoxide dismutase (MnSOD) revealed by specific staining after gel electrophoresis of cell extracts, is decreased in human fibroblasts transformed by SV40. The decrease in enzyme activity is attributable to decreased amount of enzyme protein as determined by radial immunodiffusion. Total fibroblast RNAs were translated in the presence of (35S) methionine in a cell-free translation system and the neo synthesized proteins submitted to immunoprecipitation with an anti MnSOD antiserum. Gel electrophoresis of the immunoprecipitated material followed by fluorography shows that MnSOD is translated as a peptide which is 2000 daltons larger than the mature enzyme subunit. This precursor (pre-MnSOD) is processed in vitro to mature MnSOD by the action of an isolated mitochondrial preparation. Levels of translatable MnSOD mRNA in normal and SV 40 transformed cells were compared in terms of the radioactivities incorporated into pre MnSOD bands. The results indicate that the decreased amount of MnSOD in SV 40 transformed fibroblasts is due to a decreased level of translatable mRNA for MnSOD.
Cell Transformation, Viral↗
Influence of palmitoyl-3-catechin and heptyl-3-catechin on the leucocyte migration inhibition test carried out in the presence of PPD and hepatitis B surface antigen (HBsAg).
It has been shown that (+)-cyanidanol-3 [+)-catechin) is able to stimulate in vitro the cell-mediated immune response specific for hepatitis B surface antigen (HBsAg), and might contribute to the elimination of hepatitis B virus (HBV) during HBV infection. In the present study, the possible action of two of its derivatives, palmitoyl-3-catechin and heptyl-3-catechin, on this type of immunity was investigated by adding the substances to leucocyte migration inhibition tests performed in presence of PPD and HBsAg, with leucocytes from individuals sensitized to these antigens. In normal individuals sensitized to PPD, the addition of palmitoyl-3-catechin and heptyl-3-catechin amplified the inhibition of migration by resp. 7.2% (p less than 0.05) and 13.5% (p less than 0.001). In patients previously infected by HBV and sensitized to HBsAg, the maximum amplification was resp. 12.7% (p less than 0.001) and 7.6% (p less than 0.05). This effect was dose-dependent. These substances did not modify the leucocyte migration measured in the absence of antigen. Palmitoyl-3-catechin and heptyl-3-catechin therefore seem capable of amplifying the cell-mediated immune response. The effect of the two derivatives, which were selected because of their liposolubility, was more pronounced than the effect of (+)-cyanidanol-3. It is thus possible that the two new catechin-derivatives, not yet in therapeutical use, will also stimulate cell-mediated immunity to HBsAg, and that a more marked clinical effect might be expected.
Adjuvants, Immunologic↗