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Biomedical subjects

I Liebaers

Publications and source records attributed to I Liebaers.

At least 145 records · Page 8Linked to original sources
PubMed1992

Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit.

We report the molecular characterization of a case of a functional PDH-E1 (E1 subunit of pyruvate dehydrogenase) deficiency, a cause of severe congenital lactic acidosis. Residual PDH-E1 activity was reduced to 10% of normal values, although the subunit appeared to be quantitatively and qualitatively normal at the protein level as determined by Western blotting. The sequence of PDH-E1 alpha mRNA and the corresponding genomic DNA revealed an in-frame 21-bp insertion between codons 305 and 306 of the normal E1 alpha cDNA. The mutational insert commences with a novel GAT codon and is a nearly perfect tandem duplication of the wild type DNA sequence. A serine phosphorylation site regulating the activity of the PDH complex is altered by this insertion, which in all likelihood is responsible for the functional enzymatic deficiency leading to lactic acidosis.

Acidosis, Lactic↗
PubMed1992

Preimplantation diagnosis.

Although healthy babies have been born after preimplantation diagnosis for sex determination, this technique is still in an experimental phase. To date, removal by micromanipulation of one or two blastomeres from an eight-cell embryo seems an acceptable procedure. Since a reasonable number of biopsied embryos will implant and develop in utero, the methodology for the analysis of the blastomeres at the chromosomal, gene product or DNA level, needs to be improved before further clinical application. In the meanwhile, more information about early embryo development will become available.

Animals↗
PubMed1992

Oocyte and embryo donation: evaluation of 412 consecutive trials.

A total of 199 patients (412 consecutive cycles) were treated by oocyte-embryo donation in 336 replacement cycles. Of these, 296 involved intra-uterine embryo transfers, 38 zygote intra-Fallopian transfers (ZIFT) and two gamete intra-Fallopian transfers (GIFT). Of the 336 replacements, 244 (73%) constituted transfers of fresh concepti and 92 (27%) of frozen-thawed ones. A total of 85 pregnancies were achieved of which 16 ended in preclinical abortions, giving a clinical pregnancy rate of 34.7% per patient, 20.5% per transfer and a take-home baby rate of 29.1% per patient. The pregnancy rate was significantly higher (P less than 0.05) following fresh gamete or embryo replacement (23%; 56/244) than following that of frozen-thawed embryos (14.1%; 13/92). No significant difference was observed when intra-Fallopian replacement was applied (27.5%; 11/40) as opposed to intra-uterine (19.6%; 58/296). Ovarian function was not found to be of significant importance to the achievement of pregnancies after oocyte donation since comparable pregnancy rates per replacement and per started cycle were obtained in patients with ovarian failure and in those with functional ovaries (19% and 15.4%; 24.2% and 20.2% respectively). Comparison of the implantation and abortion rates between these two groups did not reveal any significant difference (11.1% and 11.1% versus 14.8% and 16.6%). The highest pregnancy rate among patients with ovarian failure was observed in those with primary ovarian failure (26.4%; 14/53), while the lowest was among women who had received chemotherapy and/or radiotherapy (9%; 1/11).(ABSTRACT TRUNCATED AT 250 WORDS)

Embryo Transfer↗
PubMed1992

Beta-N-acetylhexosaminidase activity in human oocytes and preimplantation embryos.

beta-N-acetylhexosaminidase is a lysosomal enzyme, which has two isoenzymes: beta-Hex A, a trimer consisting of one alpha-chain and two beta-chains (alpha beta 2) and beta-Hex B, a tetramer formed of four beta-chains (beta 2 beta 2). Genetic defects in the alpha-chain lead to Tay-Sachs disease, whereas mutations in the beta-chain gene lead to Sandhoff disease. In a previous study we developed a microassay for total beta-N-acetylhexosaminidase and used this for measuring activities in mouse oocytes and preimplantation embryos. In this study, to assess the feasibility of transferring this technique to the human for the purposes of preimplantation diagnosis for Tay-Sachs and Sandhoff disease, beta-Hex activity was assayed in human oocytes and embryos and in the medium in which they had been cultured. We showed that although the activity of beta-N-acetylhexosaminidase in human oocytes and embryos was > 500 times higher than in the mouse, it was not detectable in the culture medium and the activity in oocytes and embryos remained virtually constant throughout human preimplantation development, making it difficult to distinguish embryonic from maternal enzyme activity. In the absence of this distinction it would be inappropriate to use beta-N-acetylhexosaminidase activity for the purposes of preimplantation diagnosis of Sandhoff or Tay-Sachs disease. These experiments demonstrate that measuring the beta-N-acetylhexosaminidase activity in human embryos cannot be used at present for preimplantation diagnosis.

Blastocyst↗
PubMed1991

Beta-glucuronidase deficiency as a cause of prenatally diagnosed non-immune hydrops fetalis.

We describe a case of beta-glucuronidase deficiency presenting as a non-immune hydrops fetalis diagnosed at 26 weeks of gestation. The deficiency was disclosed on cultured amniotic fluid cells and in fetal plasma and was confirmed post-abortion. In a second pregnancy, a normal beta-glucuronidase activity was found in extracts of chorionic villi obtained at 10 weeks of gestation. The pregnancy is continuing uneventfully. We conclude that it is of great importance to verify the presence of metabolic disease whenever the major causes of hydrops fetalis have been excluded.

Adult↗
PubMed1991

Beta-glucuronidase activity in mouse oocytes, mouse preimplantation embryos, and human gametes.

A microfluorimetric assay was designed to monitor beta-glucuronidase (beta-gluc) activity during the early development of mouse embryos and was also applied to measure beta-gluc activity in human sperm cells and single human oocytes. Mouse oocytes and preimplantation embryos at different stages of development, failed fertilized human oocytes, and human sperm cells were collected, and beta-gluc activity was analysed. In the mouse, beta-gluc activity could be measured starting from the morula stage on in a pooled sample of 15 embryos and at blastocyst formation in one single embryo. beta-Gluc activity was low in human sperm cells. The enzyme could be readily demonstrated in 87 per cent of non-fertilized human oocytes. Considerable variation in beta-gluc activity was noticed between individual oocytes.

Animals↗
PubMed1991

Beta-N-acetylhexosaminidase activity in mouse oocytes and preimplantation embryos.

Beta-N-Acetylhexosaminidase is a lysosomal enzyme; mutation in this protein leads to Tay-Sachs or Sandhoff disease. We have developed an assay for the beta-N-acetylhexosaminidase in mouse oocytes and preimplantation embryos. Activity was low in oocytes and zygotes and started to rise from the late 2-cell stage. By using alpha-amanitin, an inhibitor of DNA-dependent RNA polymerase, we were able to show that the first embryonic mRNA transcriptions of the beta-N-acetylhexosaminidase genes take place between 38 and 46 h post HCG (early 2-cell stage) and between 46 and 54 h post HCG (late 2-cell stage).

Amanitins↗
PubMed1991

Lysosomal storage diseases presenting as transient or persistent hydrops fetalis.

Two cases of beta-glucuronidase deficiency (mucopolysaccharidosis VII), presented with fetal hydrops at 20 and 26 weeks of gestation. The enzyme deficiency was observed in cultured amniotic fluid cells and in fetal plasma from cord-blood and was confirmed after termination of pregnancy. A third case presented with transient ascites at 6.5 months of gestation. Mild dysmorphic features at birth and gradual neurological deterioration were observed. Deficiency of beta-galactosidase was documented confirming a GM1 gangliosidosis. Evidence has accumulated that fetuses affected by lysosomal diseases, may present with transient or persistent hydrops fetalis. The exact frequency is however not known. Further diagnostic studies in persistent or transient hydrops fetalis, looking for lysosomal and other metabolic diseases, whenever major causes of hydrops fetalis have been excluded, are therefore indicated. Amniocentesis and cordocentesis should always be performed.

Chorionic Villi Sampling↗
PubMed1990

The deletion F508 is the major gene mutation in a representative Belgian cystic fibrosis population.

The cystic fibrosis (CF) gene deletion F508 was studied in a Belgian population of 74 families and their 83 CF children. The haplotypes for CF and normal chromosomes had previously been determined with several linked DNA probes. In our CF population, the gene deletion F508 was found in 76% of the mutant alleles. Of the deletion F508, 97% segregated with the highest risk haplotype for the CF carrier status. Some 61% of our families were found to be homozygous for this major CF mutation. Each of our three pancreatic sufficiency patients (two of whom were siblings) was heterozygote for the F508 deletion.

Belgium↗
PubMed1990

Allogeneic cultured epidermal grafts heal chronic ulcers although they do not remain as proved by DNA analysis.

To investigate whether allogeneic cultured keratinocytes are rejected or not, and to find out how beneficial their effect on wound healing could be, patients with chronic ulcers were grafted with allogeneic cultured human keratinocytes. In order to examine the epidermal origin of the healed wound, DNA analysis was performed and compared to donor and recipient blood-cell DNA. Healing was observed in 84% of the grafted ulcers by granulation tissue stimulation and would edge effect. In little time 60% of the grafted chronic ulcers healed completely. Although no rejection was observed, DNA analysis revealed that the grafted allogeneic keratinocytes were finally replaced by the patient's own epidermis. This study confirmed that cultured allogeneic keratinocytes that have been grafted on ulcers, play an important role in the wound healing process.

Adult↗
PubMed1989

Chromosome studies and fertility treatment in women with ovarian failure.

In vitro fertilization and embryo transfer or gamete (or zygote) intra-Fallopian transfer after ovum donation were performed in 16 patients with primary or secondary amenorrhea, associated with chromosome abnormalities. The patients showed the wide range of (mostly X) chromosome abnormalities characteristic for women with primary or premature ovarian failure. Four of these patients became pregnant and three of them have delivered healthy infants with a normal karyotype. This pregnancy rate is far superior to the accepted fertility figure in these patients. When these results were compared with the fertility treatment results of three other groups of women with absent ovarian function (1. ovarian dysgenesis; 2. surgical castration; 3. premature menopause) but with a normal 46,XX karyotype, no difference in treatment efficiency could be detected. These results offer a promising approach for the treatment of infertility in agonadal patients with chromosome aberrations.

Adult↗