Search PubMed⌕ Search

Biomedical subjects

J Lejeune

Publications and source records attributed to J Lejeune.

At least 19 recordsLinked to original sources
PubMed1998

No association between dopamine D1, D2, and D3 receptor genes and manic-depressive illness.

BACKGROUND: The dopaminergic receptor genes are candidate genes for manic-depressive illness (MDI). To test this putative involvement we used a case-control study on samples from the native population of the northwest part of France. METHODS: Fifty patients for D1 and D2, 61 patients for D3, and 86-223 controls were tested. RESULTS: No significant association was found between allelic frequencies or genotype counts and MDI, even when the data were pooled with those from published studies. CONCLUSIONS: Single mutations of either of the studied receptor genes are not major determinants of MDI.

Adult↗
PubMed1997

[Variation of amino acids in relation to age in Down syndrome subjects].

BACKGROUND: A preliminary study of plasma and urinary amino acid concentration in Down's syndrome subjects had shown some impairments. PATIENTS AND METHODS: A comparative study of the variations of amino acid concentration with age in Down's syndrome subjects aged 0 to 60 years and in control subjects aged 0 to 94 years was made in order to determine whether these impairments could be explained by generalized premature aging, or by a specific gene dosage effect. RESULTS: Two major changes (P < 0.001) were found in Down's syndrome: a decrease in plasma concentration of serine at any age, which could be due to a dosage effect of cytathionine-beta-synthase, and an increase in plasma lysine concentration in patients above 10 year's old, probably due to premature aging. Other minor changes were also present in plasma and urine, also possibly explained by premature aging. CONCLUSIONS: Other studies are necessary to evaluate possible consequences of such changes in the amino acid profiles.

Adolescent↗
PubMed1995

Excessive glutamine sensitivity in Alzheimer's disease and Down syndrome lymphocytes.

In addition to clinical and neuropathological similarities between Alzheimer's disease and Down syndrome there are genetic and biochemical data which suggest common disease mechanism. Using an in vitro assay examining variations of the mitotic index in the presence or absence of various inhibitors or metabolites of purine and/or pyrimidine synthesis, we studied 19 Alzheimer disease patients and 16 patients with both Down syndrome and Alzheimer type dementia. A highly significant decrease in mitotic index in the presence of exogenous glutamine was noted in patients presenting an Alzheimer type dementia with or without associated Down syndrome. These findings suggest that glutamine sensitivity or some dysregulation of the glutamine/glutamate pathway may play a role in the pathogenesis of Alzheimer's disease. If these findings are confirmed, they would have important implications in the development of preventive strategies.

Adult↗
PubMed1995

In vivo folic acid supplementation partially corrects in vitro methotrexate toxicity in patients with Down syndrome.

Patients with Down syndrome have been found to have characteristic in vivo and in vitro methotrexate toxicity. The in vitro methotrexate toxicity characteristic of Down syndrome can be diminished by the in vivo administration of supplemental high doses of folic acid. A possible explanation for the increased sensitivity to methotrexate which has been documented in patients with Down syndrome may be due to imbalances in nucleotide pools which result from a gene dosage effect and to greater methylation demands. Supplemental folic acid may be beneficial by virtue of a down-regulation of excess gene activity and may also provide needed monocarbons.

Adolescent↗
PubMed1994

[Metabolic anomalies in trisomy 21: a method for analyzing lymphocyte cultures].

Using a method of analysis which consists in the evaluation of the mitotic index of lymphocyte cultures to which different metabolites and anti-metabolites have been added, we studied various forms of mental retardation due to a chromosomal aberration and observed specific biochemical imbalances. Methotrexate sensitivity is characteristic of trisomy 21. A significant difference in purine synthesis pathway was observed between patients with Down syndrome without complications and those presenting with additional psychotic features. Inspite of a gene dosage effect for genes intervening in purine synthesis, lymphocytes from psychotic trisomy 21 patients seem unable to complete inosine synthesis. Lymphocytes from patients with Alzheimer's disease with or without trisomy 21 are excessively sensitive to exogenous glutamine.

Amino Acid Sequence↗
PubMed1993

Acute lymphoblastic leukemia with trisomy 21 constitutional mosaicism.

Acute lymphoblastic leukemia was diagnosed in an 11-year-old girl with mild signs of Down's syndrome. She was known since birth to have a constitutional mosaicism (46,XX/47,XX,+21c). At initial diagnosis of acute leukemia, additional chromosome changes were found in bone marrow blasts: hyperdiploidy > 50, with a structural abnormality. She was treated with a standard chemotherapeutic protocol, and has remained in complete remission for more than 3 years. The constitutional mosaicism evolved toward normalization year after year in the blood and under the effect of chemotherapy in the bone marrow.

Child↗
PubMed1993

Differences in purine metabolism in patients with Down's syndrome.

Three enzymes intervening in de novo purine synthesis, as well as cystathionine B-synthetase, have been mapped to chromosome 21. In order to gain a better understanding of purine synthesis anomalies in Down's syndrome, the present authors studied the variations in mitotic index of lymphocyte cultures to which various inhibitors or metabolites of purine synthesis had been added. In spite of common gene dosage effects, unexpected and highly significant differences were noted between Down's syndrome patients without complications and those presenting with additional psychotic features. In Down's syndrome patients without complications, a highly significant decrease in mitotic index was noted in the presence of exogenous inosine. A significant decrease in the presence of adenosine and guanosine was also noted. These findings are in keeping with the expected metabolic repercussions of genes mapped to chromosome 21. In Down's syndrome patients with psychotic complications, the in vitro reactions were quite different. A paradoxal increase in mitotic index was noted in the presence of inosine and of adenosine, but the response to guanosine did not differ from that observed in normal controls. These findings were unexpected and seem to indicate that, in spite of the gene dosage effect, psychotic Down's syndrome patients are unable to compensate abnormal purine synthesis and resulting imbalances. Furthermore, a marked difference in purine metabolic reactions was noted between Down's syndrome patients receiving supplemental folic/folinic acid and those on no therapy. This suggests that some modulation of the gene dosage effect may be possible.

Adenosine↗
PubMed1993

[Brain morphometry using MRI in Cri-du-Chat Syndrome. Report of seven cases with review of the literature].

The authors present the results of a morphometric study of the brain of 7 patients with cat cry syndrome, explored with Magnetic Resonance Imaging (MRI). A method is proposed in order to facilitate the identification of the anatomical slices. A characteristic anomaly is observed as a marked atrophy of the brainstem predominating at the pontine level and associated with a small cerebellum, atrophic middle cerebellar peduncles and cerebellar white matter. This apparently systematized atrophy obvious in children, seems similar to the one observed in patients presenting a olivopontocerebellar atrophy, possibly correlating with disturbance of coordination and developmental delay in motility as observed in these patients. This does not implicate the same subjacent functional neuroanatomical pathways.

Adolescent↗
PubMed1992

Segregation of three reciprocal translocations in the same family: t(3;4), t(5;10), and t(15;21).

A male infant with static antenatal encephalopathy and epilepsy was found to have a duplication of 5p12----5pter and deficiency of 10p13----10pter. Each of his parents was a carrier of a balanced reciprocal translocation. A third translocation was found in the maternal grandfather. The pedigree of each translocation and the segregation of parental reciprocal translocations are discussed.

Amino Acids↗
PubMed1992

Reduced sensitivity to dexamethasone of pancreatic islets from obese (fa/fa) rats.

The direct effects of dexamethasone exposure on insulin secretion from islets of fa/fa rats and their lean littermates (Fa/?) were compared. After 72 h culture in 1 nM dexamethasone, glucose (27.5 mM)-stimulated insulin secretion over 90 min from islets of lean rats was significantly decreased compared with islets cultured without dexamethasone (12.9 +/- 1.4 vs. 5.7 +/- 1.0% of total islet content, p < 0.05). Higher doses of dexamethasone for 24-48 h culture produced similar effects. For islets of fa/fa rats, the minimum inhibitory concentration of dexamethasone was 10-fold higher, and islets required at least 48 h exposure for inhibitory effects to be observed. Dexamethasone also decreased the insulin response by islets to glybenclamide, indicating that dexamethasone effects were not specific to glucose transport or metabolism. The results suggest that islets of fa/fa rats may be less sensitive to direct inhibitory effects of glucocorticoids on glucose-stimulated insulin release than islets of lean animals.

Animals↗
PubMed1992

No significant effect of monosomy for distal 21q22.3 on the Down syndrome phenotype in "mirror" duplications of chromosome 21.

Three Down syndrome patients for whom karyotypic analysis showed a "mirror" (reverse tandem) duplication of chromosome 21 were studied by phenotypic, cytogenetic, and molecular methods. On high-resolution R-banding analysis performed in two cases, the size of the fusion 21q22.3 band was apparently less than twice the size of the normal 21q22.3, suggesting a partial deletion of distal 21q. The evaluation of eight chromosome 21 single-copy sequences of the 21q22 region--namely, SOD1, D21S15, D21S42, CRYA1, PFKL, CD18, COL6A1, and S100B--by a slot blot method showed in all three cases a partial deletion of 21q22.3 and partial monosomy. The translocation breakpoints were different in each patient, and in two cases the rearranged chromosome was found to be asymmetrical. The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1-S100B, CD18-S100B, and PFKL-S100B. DNA polymorphism analysis indicated in all cases a homozygosity of the duplicated material. The duplicated region was maternal in two patients and paternal in one patient. These data suggest that the reverse tandem chromosomes did not result from a telomeric fusion between chromosomes 21 but from a translocation between sister chromatids. The phenotypes of these patients did not differ significantly from that of individuals with full trisomy 21, except in one case with large ears with an unfolded helix. The fact that monosomy of distal 21q22.3 in these patients resulted in a phenotype very similar to Down syndrome suggests that the duplication of the genes located in this part of chromosome 21 is not necessary for the pathogenesis of the Down syndrome features observed in these patients, including most of the facial and hand features, muscular hypotonia, cardiopathy of the Fallot tetralogy type, and part of the mental retardation.

Adult↗
PubMed1992

[Amino acids and trisomy 21].

The relative concentrations of plasmatic and urinary amino acids were analysed in 79 trisomic-21 patients, 322 mentally retarded non-trisomic patients, and 206 controls. No true amino acidopathy was found in 21-trisomy, but in plasma a deficit of serine and an excess of cysteine and lysine are highly significant. Excesses of cysteine, methionine, tyrosine, and methyl-histidine are also typical in urine. The increased activity of superoxide-dismutase, cystathionine-beta-synthase, and purine synthesis enzymes, together with the sensitivity to methotrexate, atropine, and dysthyroidism, are in accordance with this shift of equilibrium. A nutritional compensation seems worth investigating.

Amino Acids↗
PubMed1991

Metabolic anomalies in cri du chat syndrome (5p-) lymphocytes and de novo purine synthesis.

Having previously demonstrated that patients with cri du chat, 5p- syndrome, have a highly significant excess of the plasmatic and urinary relative amount of asparagine and aspartate, the authors tested the hypothesis according to which this excess could be in relation with a defect of purine metabolism. Using a previously reported in vitro assay, they found a paradoxal increase in the mitotic index in the presence of L-alanosine in lymphocyte cultures of patients with 5p- who were on no medication. They also observed particularly severe toxicity to HAT medium. This response, apparently characteristic for 5p- syndrome, was highly significant when compared to the one observed in samples of normal controls, of patients with mental retardation of various etiologies, patients with Down syndrome or with Xqfra syndrome. When patients with cri du chat syndrome received inosine with folinic acid, an inversion of their response to alanosine was observed as well as the normalization of their response to HAT medium. These findings suggest that deletion of 5p14-5p15 leads to some impairment of de novo purine synthesis, the implications of these findings are discussed.

Adolescent↗
PubMed1991

[The pathogenesis of mental retardation in trisomy 21].

An adequate number of nerve cells, their connection by dendrites and axons, the transmission of information by chemical mediators are all necessary for normal brain function. Monocarbonic acid residues, purines and pyrimidines and tubulins and biopterin are essential to ensure that the necessary chemical processes can take place. In trisomy 21 the metabolism is disturbed by the enhancement of individual enzyme activities. Particular clinical effects suggest specific therapeutic interventions. The effects can be influenced by way of the monocarbonic acid metabolisms. The action of thyroxine is especially interesting, as it inhibits the disintegration of monocarbonic acids.

Amyloid beta-Protein Precursor↗
PubMed1991

[Pathogenesis of mental impairment in trisomy 21].

Short of discovering how to silence selectively one of the 3 chromosomes 21, no rational medication can be envisaged before pathogenesis has been unraveled, at least partially. A biochemical scheme of impairment of mental efficiency is presented, and the possible deleterious effects of a given gene overdose are discussed. Cu/Zn SOD, cystathionine beta synthase, S 100 beta protein, phosphofructokinase, purine synthesis and adenosine pharmacology, thyroid disturbance, and elevated TSH with low rT3 as well as biopterin metabolism interferences are reviewed. These metabolic paths are tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutual regulation. Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate, and systematic research of special sensitivities has begun. Clinical observations and relevant statistical methods allow study of the speed of mental development under various medications. The interest of regulating thyroid metabolism, when needed, is exemplified. Re-equilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo Alzheimer complication is presented.

Chromosome Mapping↗