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Biomedical subjects

I Liebaers

Publications and source records attributed to I Liebaers.

At least 163 records · Page 9Linked to original sources
PubMed1988

Severe congenital cutis laxa with pulmonary emphysema: a family with three affected sibs.

Clinical and morphologic findings in 3 sibs with congenital cutis laxa are presented. A severe urinary malformation in one affected infant is reported in detail. Elevated serum copper concentrations were observed in 2 of the sibs and in the healthy mother. However, the 64Cu uptake of fibroblast cells from tissue culture was not increased. Ultrastructural pathologic findings from skin biopsies have been studied and compared at birth and at age 2 years. The lack of junction between the 2 elastic fiber components was similar. Further evidence for clinical heterogeneity of this disease is stressed.

Cutis Laxa↗
PubMed1988

Prenatal diagnosis of Hunter syndrome using fetal plasma.

The X-linked Hunter syndrome or mucopolysaccharidosis II was diagnosed in a male fetus by demonstrating a severe deficiency of iduronate 2-sulphate sulphatase activity in fetal plasma obtained by umbilical fetal blood sampling at 23 weeks of pregnancy. The diagnosis was confirmed after termination of pregnancy.

Female↗
PubMed1988

The role of fluorinated pyrimidine analogues in the induction of the in vitro expression of the fragile X chromosome.

The modes of action of 5-fluoro-2'-deoxyuridine (FdUrd) and 5-fluoro-2'-deoxycytidine (FdCyd) were studied in PHA-stimulated lymphocytes from normal volunteer donors and a fragile X patient. In both cell types, FdUrd and FdCyd inhibited cell proliferation at concentrations of 3 x 10(-8) M. Thymidylate synthetase was identified as the decisive target for the action of both FdUrd and FdCyd, as judged from the following observations: First, addition of thymidine to the culture medium was able to counteract both FdUrd and FdCyd toxicities, whereas addition of dCyd had no observable effect. Second, inhibition of the in situ thymidylate synthetase activity measured as an increase in the level of [3H]-dThd incorporation coincided with the inhibition of cell proliferation. Third, the inhibition of the thymidylate synthetase-dependent incorporation of [3H]-dUrd into newly synthesized DNA coincided with the inhibition of cell proliferation. The effects of FdUrd and FdCyd on the in vitro expression of fragile site Xq27 of fragile X chromosomes was shown to be based on the depletion of the intracellular pool of thymidine-5'-monophosphate (dTMP), as judged from the following observations: First, both the FdUrd- and FdCyd-dependent induction of site Xq27 coincided with the antiproliferative effects of the respective fluoropyrimidines. Second, addition of thymidine (dThd) to the culture medium both prevented the expression of site Xq27 and neutralized the cytotoxicity of FdUrd and of FdCyd. On the basis of these findings, we provide further evidence for the concept that the fragile X site is located in an AT-rich region.

Base Composition↗
PubMed1988

Chromosome aberrations in 500 couples referred for in-vitro fertilization or related fertility treatment.

Cytogenetic studies were performed in 500 couples referred for in-vitro fertilization or gamete (zygote) intra-Fallopian transfer. Thirteen individuals (1.3%) with chromosomal abnormalities were found. Four major types of anomalies were observed: reciprocal translocations (n = 3), inversions (n = 2), iso-Xq chromosomes (n = 2) and sex chromosome number mosaics (n = 4). Moreover two males with respectively a 47,XYY and a 47,XY,mar+ karyotype were identified. These data pointed to a higher incidence of chromosomal aberrations in this infertile population as compared to a neonatal population without obvious chromosomal pathology. Analysis of the chromosomes which were involved in hyperdiploidy and hypodiploidy in the 30,000 metaphases evaluated, showed a high proportion of cells that had lost or gained an X-chromosome. A puzzling finding was the statistically significant low incidence of 45,X metaphases (0.9%) in women of couples treated on andrological indication as compared to the frequency of 45,X chromosome complements in women with tubal disease (4.0%) or of couples with an idiopathic (4.3%) or mixed female and male (6.7%) indication.

Adult↗
PubMed1988

Oocyte donation in patients without ovarian function.

The clinical, hormonal and cytogenetic findings in 36 women with primary ovarian failure, referred for oocyte or embryo donations are reported. Fifteen women were suffering from ovarian dysgenesis and 11 from premature menopause. Six of these 26 patients showed X-chromosome abnormalities. One patient had a Noonan syndrome. The remaining 10 had surgical menopause. The mean duration of their infertility was 6.5 +/- 3.2 years (+/- SD). All patients had elevated serum gonadotrophins within the menopausal range. Hypothalamic, pituitary and thyroid function were found to be intact. In one of the 15 ovarian biopsies on the patients with chromosomal competent ovarian failure, primordial follicles were found. Hysterosalpingograms revealed a normal uterine cavity in all patients. In view of oocyte donation, careful evaluation of the obstetric risk was mandatory in the six patients with X-chromosome aberrations and in the patient with the Noonan syndrome, because of their short stature and possible concomitant cardiovascular and renal disease. After substitution therapy with oestradiol valerate and natural progesterone, 13 pregnancies were established, seven patients delivered (one set of twins), eight healthy children were born, three pregnancies aborted and three pregnancies are progressing normally.

Adult↗
PubMed1988

Chorionic gonadotrophin-beta mRNA, a trophoblast marker, is expressed in human 8-cell embryos derived from tripronucleate zygotes.

Human chorionic gonadotrophin beta (HCG-beta) is a trophoblast marker. Its expression is normally limited to syncytiotrophoblast cells of chorionic villi, although it is known to be secreted from the human embryo as early as 7 days post-fertilization. To examine the onset of embryonic transcriptional activity of the gene encoding this polypeptide we have performed in-situ hybridization to cellular RNAs of human tripronucleate preimplantation embryos. We see expression of HCG-beta RNA at the 6-8-cell stage, before morphological differentiation between trophectoderm and inner cell mass is apparent. We believe that this RNA is the product of de novo transcription from the embryonic genome, since transcripts are only observed in embryos of at least 2 days post-fertilization in age.

Blastocyst↗
PubMed1987

First trimester prenatal diagnosis of lysosomal storage disease. Study of alpha-L-fucosidase isoenzyme patterns in fetal and maternal tissue.

The normal range of activities of 6 lysosomal enzymes was determined in extracts of chorionic villi samples obtained by a rigid forceps in the first trimester of pregnancy. These activities were compared to those in villi obtained after abortion and in cultured amniotic fluid cells and fibroblasts. For five of the six enzymes tested, the data suggest that first trimester prenatal diagnosis should be possible and reliable. For the sixth enzyme, alpha-L-fucosidase, where on occasion very low activities were found, the results obtained on fresh chorionic villi have to be interpreted with extreme caution. Considerable lysosomal enzyme activities were also found in maternal decidua. Therefore, extreme care must be taken in the preparation of chorionic villi for prenatal diagnosis of lysosomal disorders since even small amounts of maternal tissue could lead to misdiagnosis. This study has allowed us to monitor 2 pregnancies at risk for lysosomal storage disease. Differences in the isoenzyme pattern of alpha-L-fucosidase were found in chorionic villi and maternal decidua. Although further studies are required, this observation could lead to the development of immuno-biochemical methods to evaluate the purity of chorionic villi used for prenatal diagnosis.

Amniotic Fluid↗
PubMed1986

Pathological pregnancies. Results of amniotic fluid studies and fetal outcome.

Late amniocenteses (greater than 20 weeks' gestation) were performed in 114 pregnancies with no a priori genetic risk, but referred because of abnormal clinical and/or ultrasound findings suggesting fetal malformations. Reasons for referral included polyhydramnios (51 cases), oligohydramnios (15 cases), fetal growth retardation (FGR) (16 cases) and abnormal fetal ultrasound findings excluding anencephaly (32 cases). In 42 of these cases, referral was motivated by a combination of the above abnormal findings. When polyhydramnios was the sole anomaly (25 cases), 5 fetuses were malformed (20%), abnormal fetal karyotype and/or elevated amniotic fluid alphafetoprotein (AFP) were demonstrated in 2 cases. Oligohydramnios was the sole anomaly in one case; the infant died of prematurity. Fetal growth retardation was the sole anomaly in 14 cases, 11 otherwise normal newborns were small for date, 2 died at birth and 1 was malformed (1/14, 7%). In this group all fetal karyotypes were normal and in 2 cases amniotic fluid AFP were increased. In the 32 pregnancies without abnormal amniotic fluid volume and/or FGR and with fetal malformation(s) suggested by ultrasound, all malformations except one (ovarian cyst possibly ruptured during birth) were confirmed at birth, amniotic fluid AFP was elevated, and/or karyotype was abnormal in 6 cases. In 42 pregnancies where more than one alarm sign was present, abnormal karyotype and/or elevated amniotic fluid AFP level were recorded in 21 of the 39 cases where amniocentesis was performed, 33 fetuses were malformed (79%) and 13 died in the perinatal period (31%). The high incidence of abnormal results of amniocentesis found in this survey of pathological pregnancies, particularly in those with multiple alarm signs, emphasizes the need for amniocentesis in these situations.

Congenital Abnormalities↗
PubMed1985

Demonstration of human alpha-L-fucosidase polymorphism by means of monoclonal antibodies.

Conventional rabbit antibodies and mouse monoclonal antibodies were raised to alpha-L-fucosidase purified from human placenta. Four monoclonal antibodies were studied, of which only one (A) was able to immunoprecipitate the fucosidase activity completely. Two antibodies (B and C) precipitated 65% and one (D) 35% of the activity. The enzyme precipitated by the monoclonal antibodies remained fully active, whereas the enzyme precipitated by conventional antibodies was partly inactivated. As shown by the method of successive immunoprecipitations, the monoclonal antibodies B and C recognized the same set of placental fucosidase molecules, and D a subset thereof. The purified fucosidase also yielded two components after gel electrophoresis in nondenaturing conditions, and the slower component corresponded to the set recognized by antibodies B and C. The fucosidase extracted from different tissues and serum was studied by immunoprecipitation. In all cases, the enzyme was completely precipitated by monoclonal antibody A. Two patterns were found with B, C and D: either part of the activity was precipitated by these antibodies (leucocytes, placenta, brain, liver, spleen, thymus) or B, C and D failed to precipitate any of the enzyme (serum, heart, kidney, testes).

Animals↗
PubMed1985

Neonatal hepatitis with obstructive jaundice in an SZ heterozygous alpha 1-antitrypsin-deficient boy and destructive lung disease in his SZ mother. A review of the literature.

SZ-Alpha 1-antitrypsin deficiency, leading to severe transient neonatal cholestasis with mild hepatitis is rare. In our patient, intrahepatic bile duct hypoplasia was suspected. Since cholecystography and hepatic scintigraphy failed to reveal intrahepatic bile ducts, a diagnostic surgical liver biopsy was performed. Typical intrahepatocytic PAS-positive granules and a low serum alpha 1-antitrypsin concentration allowed a correct diagnosis of the SZ phenotype. The administration of an elementary diet quickly improved the clinical condition of our patient. Follow-up studies of this case and others will allow a better establishment of prognostic criteria and help in genetic counselling.

Adult↗
PubMed1984

Polyclonal antibodies against iduronate 2-sulphate sulphatase from human urine.

Human iduronate 2-sulphate sulphatase (EC 3.1.6.-) from urine has been purified by affinity chromatography on concanavalin A-Sepharose, ammonium sulphate fractionation and DEAE-cellulose chromatography. With ion-exchange chromatography, the enzyme was resolved in two activity peaks. The less anionic of these forms was further purified by polyacrylamide gel electrophoresis under non-denaturing conditions. Anti-iduronate 2-sulphate sulphatase antibodies were obtained from mice immunized with polyacrylamide eluted enzyme. The specificity of the antibodies towards iduronate 2-sulphate sulphatase was demonstrated by immunoprecipitation of the enzyme from partially purified urine protein. The procedure described in this work opens the way to the application of hybridoma technology to iduronate 2-sulphate sulphatase.

Animals↗
PubMed1984

Neonatal myotubular myopathy with a probable X-linked inheritance: observations on a new family with a review of the literature.

During the 3 weeks of his life, an infant born at term presented pronounced hypotonia, areflexia and generalized paresis with severe respiratory and feeding problems. He was the fourth male in two generations to die in the perinatal period, therefore suggesting an X-linked inheritance. Post-mortem examination revealed a centronuclear or myotubular myopathy. The difficulty in distinguishing the signs due to muscle disorder from those due to hypoxaemic encephalopathy is stressed. Infants with centronuclear myopathy have in any case a high risk for hypoxaemic encephalopathy. The literature concerning neonatal centronuclear myopathy with X-linked inheritance is reviewed.

Biopsy↗
PubMed1984

Prenatal diagnosis of inborn errors of metabolism. Present status and new approaches.

The evolution of the techniques aiming at the prenatal diagnosis of inborn metabolic disorders has closely reflected the progress in the knowledge of their underlying molecular defects. Initially, abnormal metabolites have been looked for in amniotic fluid. Recently, improved techniques of detection have permitted fast and reliable prenatal diagnoses through biochemical studies of cell-free amniotic fluid. Presently, the most widely used approach is the search for the defective gene product in cultured amniotic cells obtained through amniocentesis. Because of its relative safety, this procedure should be recommended, provided three prerequisites are met: a most accurate diagnosis of the index patient, the knowledge of the defective enzyme and its expression in cultured cells. For a correct interpretation of the results, cell culture parameters as well as specific activities of the mutant enzyme in the index case and the parental cells must be taken into account. Fetal blood sampling is a valuable alternative for some of the genetic disorders that cannot be detected in cultured amniocytes. The recently developed technique of chorion biopsy enables now to sample fetal cells during the first trimester of gestation. Meanwhile, the progress in DNA technology has uncovered exciting perspectives for the prenatal diagnosis of monogenic disorders at the gene level. Restriction endonuclease mapping has enabled to diagnose prenatally some forms of haemoglobinopathies, first through the polymorphism of sequences adjacent to the beta-globin gene, and now for the sickle-cell disease, by direct identification of the mutation.

Amniocentesis↗
PubMed1981

Multiple sulphatase deficiency with early onset.

This male infant was first brought to attention in the neonatal period because he presented clinical and radiological evidence of multiple bone deformities. He was readmitted at 21/2 months for hydrocephaly, hepatosplenomegaly and poor somatic and psychomotor development. In addition, coarse facies, corneal opacities and stiff joints were noticed. Bone X-ray anomalies and vacuolized lymphocytes supported the clinical presumption of lysosomal storage disorder. The diagnosis of multiple sulphatase deficiency rests on the presence of MPS and sulphatides in the urine, the finding of a mixed storage process in conjunctival biopsy and the demonstration of deficiencies in arylsulphatases A, B, C, iduronate sulphatase and heparan sulphatase in serum, leukocytes and cultured fibroblasts.

Abnormalities, Multiple↗