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M Goossens

Publications and source records attributed to M Goossens.

At least 199 records · Page 11Linked to original sources
PubMed1988

Comparison of genetic probe with immunophenotype analysis in lymphoproliferative disorders: a study of 87 cases.

We examined 91 specimens (from 87 patients) for the expression of B-cell- and T-cell-associated differentiation antigens and rearrangements of the Ig and beta-chain of the T-cell (beta-TCR) genes. Of these, 74 were representative of various histologic subtypes of non-Hodgkin's lymphoma and related disorders, 11 of Hodgkin's disease, and 6 of reactive lymphoid hyperplasia. An Ig gene clonal rearrangement correlated to a monotypic (kappa/lambda) phenotype in 32 of 33 histologically defined lymphoma samples. The genotypic analysis also confirmed clonality in six of seven malignant diffuse lymphomas that were nonmonotypic but expressed pan-B antigens; in four, more than one clone was detected within individual tumors. A beta-TCR clonal rearrangement was found in 19 of 19 tumor samples considered as malignant T-cell lymphoma on the basis of histopathology and of the CD3-positive phenotype of tumoral cells, and in two cases of CD3-positive lymphomatoid disorders. A loss of pan-T antigens (CD7, CD5, CD2, CD4/CD8) was observed in all but three of these CD3-positive samples. Such an incomplete T-cell phenotype always correlated to the presence of a monoclonal process as revealed by genotypic analysis. DNA analysis was the only way to demonstrate clonality in other samples with either a polymorphous (partial involvement, pseudolymphoma, angioimmunoblastic lymphodenopathy [AILD]) or an undifferentiated (large cell anaplastic) phenotype. It is concluded that although in the majority of cases immunophenotyping alone provides criteria adequate for the diagnosis of lymphoid malignancy, in some, particularly polymorphous or large cell anaplastic processes, genetic probe analysis was additionally discriminative.

Antigens, Differentiation↗
PubMed1988

[Prenatal diagnosis and genetic diseases of the lung].

Currently two genetic pulmonary disorders can be diagnosed before birth: alpha-1-antitrypsin deficiency and mucoviscidosis. For the latter there are two possible diagnostic techniques: first a study of the intestinal enzymes of the amniotic fluid, a reliable method only at the 18th week, and also a study of DNA markers (ADN) of the trophoblastic cells using molecular biological techniques: this can be performed from the 10th to 11th week of pregnancy but presupposes a family study in which there is already a subject suffering from the disorder. Foetal echocardiography enables various pulmonary abnormalities to be detected: pleural effusion, cyst, pulmonary hypoplasia and other disorders. This technique however has some limits, at least at present. Most often these severe malformations are revealed at birth such as respiratory distress or stillbirth. Adenomatous cystic malformations or congenital lobar emphysema, a posterior diaphragmatic hernia, and oesophageal atresia with oesophagotracheal fistula are the most frequent and are curable surgically.

Amniotic Fluid↗
PubMed1988

[Detection of residual disease in onco-hematology: the contribution of molecular biology].

The development of the tools of recombinant DNA technology has implications for clinical oncology. We briefly describe in this article the use of DNA probes as diagnostic tools for the study of leukemias and other malignancies and for the detection of minimal residual disease. Useful DNA markers can be used to assess successful engraftment in bone marrow transplanted patients and to detect mixed chimerism. Immunoglobulin and T cell receptor gene rearrangements can be analysed to investigate the presence of clonal lymphoid populations with pathologic samples and to determine their B or T cell lineage. Point mutations associated with oncogene activation can be detected by hybridization with allele specific oligonucleotide probes, allowing molecular analysis of certain tumors. The level of sensitivity of the different assays are discussed along with their usefulness in the detection of residual malignant cells after appropriate therapy.

Bone Marrow↗
PubMed1987

DNA polymorphism of human porphobilinogen deaminase gene in acute intermittent porphyria.

A common two-allele MspI restriction fragment length polymorphism of the human erythroid porphobilinogen (PBG)-deaminase gene was investigated in 33 unrelated patients with acute intermittent porphyria (AIP) and 20 controls. The polymorphism was tightly linked (lod score 3.14; no recombinants) to the locus for AIP as identified by measurement of erythrocyte PBG-deaminase activity. The frequency of the polymorphism in the AIP patients did not differ significantly from that in the controls. No common polymorphisms for eight other restriction endonucleases were found in either group. In 30 of the AIP patients no crossreacting immunological material (CRIM) was produced by the mutant PBG-deaminase allele. The MspI polymorphism enabled each PBG-deaminase allele to be distinguished in subjects heterozygous for the polymorphism; thus a major gene deletion was excluded as the cause of the CRIM-negative mutation in all of the 18 families that contained an affected CRIM-negative individual heterozygous for the polymorphism. In suitable families, the MspI polymorphism provides a more certain way of identifying carriers of the AIP gene than current enzymatic methods and major gene deletions are unlikely to be present in more than a small proportion of the commonest type of AIP, the CRIM-negative form.

Acute Disease↗
PubMed1987

Structure of the gene for human uroporphyrinogen decarboxylase.

Uroporphyrinogen decarboxylase, the fifth enzyme of the heme biosynthetic pathway, is an housekeeping enzyme whose activity is enhanced during erythropoietic differentiation. We have previously shown that this increased activity was in part accounted for by an enhanced transcription of the gene in erythropoietic tissues. To elucidate further the tissue specific regulation of an housekeeping gene we have isolated the human URO-D gene and determined its organization. The cloned gene comprises 10 exons spread over 3 Kb. Two transcriptional start sites were determined and analysis of 900 bp of the 5' flanking region suggests a very simple structural organization for the URO-D gene promoter. We also show that this gene is functional when transfected into mouse fibroblasts, and that its promoter is sensitive to a viral enhancer.

Animals↗
PubMed1987

Mixed blood chimerism in T cell-depleted bone marrow transplant recipients: evaluation using DNA polymorphisms.

We have used DNA sequence polymorphism analysis to document engraftment after T cell-depleted bone marrow transplantation (BMT), with a selected panel of four DNA probes. In contrast to nondepleted BMT recipients, the patients who received T cell-depleted marrow exhibited a mixed blood chimerism. This mosaicism was observed before graft failure or relapse in six patients. However, in five other patients, this mixed chimerism was not followed by these complications with a follow-up of 9 to 31 months after transplantation. Our results support the hypothesis that transplanted bone marrow T cells may help to maintain engraftment by eliminating host cells that can cause graft failure.

Adult↗
PubMed1986

Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase.

We have cloned and sequenced a cDNA clone coding for human erythrocyte porphobilinogen deaminase. It encompasses the translated region, part of the 5' and the 3' untranslated regions. The deduced 344 amino acid sequence is consistent with the molecular weight and the partial amino-acid sequence of the NH2 terminal of the purified erythrocyte enzyme. Southern analysis of human genomic DNA shows that its gene is present as a single copy in the human genome and Northern analysis demonstrates the presence of a single size species of mRNA in erythroid and non-erythroid tissues and in several cultured cell lines. Quantitative determinations indicate that the amount of PBG-D mRNA is modulated both by the erythroid nature of the tissue and by cell proliferation, probably at the transcriptional level.

Amino Acid Sequence↗
PubMed1986

Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA.

We have cloned and sequenced a full-length cDNA coding for human uroporphyrinogen decarboxylase. The deduced 367-amino acid sequence is consistent with the molecular weight, the partial amino acid sequence of cyanogen bromide peptides, and the total amino acid composition of the purified enzyme. Southern analysis of human genomic DNA shows that its gene is present as a single copy in the human genome, and Northern analysis demonstrates the presence of a single size species of mRNA in erythroid and non-erythroid tissues and in several cultured cell lines. We have also demonstrated that the level of uroporphyrinogen decarboxylase mRNA is markedly increased in tissues or cell lines of erythroid origin and that this is due to a tissue-specific transcriptional activation of the uroporphyrinogen decarboxylase gene.

Amino Acid Sequence↗
PubMed1986

Molecular cloning and sequencing of the human erythrocyte 2,3-bisphosphoglycerate mutase cDNA: revised amino acid sequence.

The human erythrocyte 2,3-bisphosphoglycerate mutase (BPGM) is a multifunctional enzyme which controls the metabolism of 2,3-diphosphoglycerate, the main allosteric effector of haemoglobin. Several cDNA banks were constructed from reticulocyte mRNA, either by conventional cloning methods in pBR322 and screening with specific mixed oligonucleotide probes, or in the expression vector lambda gt 11. The largest cDNA isolated contained 1673 bases [plus the poly(A) tail], which is slightly smaller than the size of the intact mRNA as estimated by Northern blot analysis (approximately 1800 bases). This cDNA encodes for a protein of 258 residues; the protein yielded 34 tryptic peptides which were subsequently isolated by h.p.l.c. Our nucleotide sequence data were entirely confirmed by the amino acid composition of these tryptic peptides and reveal several major differences from the published sequence; the revised amino acid sequence of human BPGM is presented. These findings represent the first step in the study of the expression and regulation of this enzyme as a specific marker of the erythroid cell line.

Amino Acid Sequence↗
PubMed1986

Assignment of human uroporphyrinogen decarboxylase (URO-D) to the p34 band of chromosome 1.

A cDNA probe corresponding to mRNA encoding human uroporphyrinogen decarboxylase (URO-D) was used to determine the chromosomal localization of the URO-D gene in the human genome. In agreement with previous studies, we have found that the locus for URO-D is located on chromosome 1 in hybrid cell mapping panels. The use of in situ hybridization allowed us to map the URO-D locus to band 1p34.

Animals↗
PubMed1986

Molecular analysis of uroporphyrinogen decarboxylase deficiency in a family with two cases of hepatoerythropoietic porphyria.

In order to determine the molecular basis of uroporphyrinogen (URO) decarboxylase deficiency responsible for hepatoerythropoietic porphyria (HEP) and familial porphyria cutanea tarda, we used a human URO decarboxylase cDNA to analyze the organization and expression of the URO decarboxylase gene in lymphoblastoid cells from normal individuals and from two patients with HEP. We could detect neither deletions nor rearrangements in the URO decarboxylase gene. Synthesis, processing, and cell-free translation of the specific transcripts appeared to be normal. The half-life of the abnormal protein was 12 times shorter than that of the normal enzyme. The results indicate that the enzyme defect is due to a rapid degradation of the protein in vivo. This study is the first to provide information regarding the molecular mechanism responsible for the URO decarboxylase deficiency in HEP.

Carboxy-Lyases↗
PubMed1986

Isolated growth hormone (GH) deficiency type 1A associated with a double deletion in the human GH gene cluster.

The gene deletions responsible for isolated GH deficiency type 1A were characterized by direct analysis of genomic DNA prepared from the leukocytes of two affected children. The probands had typical symptoms of severe isolated GH deficiency complicated by antibody development and growth arrest after human (h) GH treatment. DNA analysis using the restriction endonucleases Eco RI, Bam HI, and Hind III revealed that the restriction fragment containing the hGH-N gene was absent along with those bearing the human chorionic somatomammotropin (hCS)-A and -B and hGH-V sequences. A total of about 40 kilobases DNA were absent due to two separate deletions flanking the hCS-L gene. The two affected siblings are homozygous for this rearrangement of the hGH/hCS gene cluster, which could have been generated by homologous crossing over between two different chromosomes, one bearing one of the previously described deletions of the hGH-N gene, and one bearing a deletion of DNA containing the hCS-A, hCS-B, and hGH-V sequences. Alternatively, this abnormality could have been generated by a complex intrachromosomal rearrangement. The parents, who are consanguinous, have DNA restriction patterns consistent with heterozygosity for this double deletion. This type of deletional mutation is the first involving multiple deletion of the hGH and hCS gene cluster.

Adolescent↗
PubMed1986

A de novo intragenic deletion of the potential EGF domain of the factor IX gene in a family with severe hemophilia B.

We have studied a family of three patients who were severely afflicted with hemophilia B without inhibitor for their factor IX genes through the use of factor IX cDNA and genomic DNA probes. The patients had detectable (30% of normal) factor IX antigen. DNA hybridization analysis demonstrated that these patients had a partial intragenic deletion in their factor IX gene. This 2.8-kb deletion included exon d and the surrounding sequences. This exon codes for the amino acid sequence from No. 47 through 84 of the factor IX protein and contains its first potential EGF domain; the de novo occurrence of the mutation in the grandfather's germ cells was established by linkage analysis. This specific gene has been named F IXStrasbourg.

Chromosome Deletion↗
PubMed1986

[Familial type of hypophyseal nanism. Apropos of 7 families in western Algeria].

Eighteen pituitary dwarfs belonging to 7 different West Algerian families were studied. Eleven patients from 4 families presented isolated growth hormone deficiency, 7 patients from 3 families had multiple pituitary hormone deficiencies. Serum GH levels before and after standard pharmacological stimulations were below 2 ng/ml in all cases. Three of 10 hGH treated patients increased significantly their growth rate (8.5 +/- 0.5 cm/year) during the first year of treatment; growth was moderate (5.3 +/- 0.8 cm/year) in 3 patients and poor (4.5 cm/year) in 2 patients. In 2 cases the follow-up is insufficient.

Adolescent↗
PubMed1986

[hGH and molecular biology].

This review summarizes the progress recently made through the approaches provided by DNA recombinant technology in the knowledge of the human growth hormone (hGH) gene and of the molecular basis of hGH deficiencies. The growth hormone gene is part of a family of five structural genes located on the long arm of human chromosome 17, over a distance of 55 kilobases (kb), and oriented in the same transcriptional 5' to 3' direction in the order 5' hGH-N, hCS-L, hCS-A, hGH-V, and hCS-B 3'. The five genes contain five exons interrupted by four introns, and they display a high sequence homology. GH and CS genes show class differences on their 3' side, approximately 100 base pairs beyond the polyadenylation sites. Analysis of homology regions has permitted to define duplication units useful to trace the evolution process of the cluster. The hGH-N gene codes for the normal, pituitary, 22K human growth hormone. The hGH-V genes codes for a variant peptide that can be expressed in vitro in transgenomic systems, but that is not known to be expressed in vivo. The hCS-A and -B genes each code for human chorionic somatomammotropin. They specify the same mature hormone and are expressed at different levels in term placenta. The hCS-L gene appears to be an unexpressed pseudogene and has a single base substitution, located in a splicing site, that would preclude normal mRNA maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗