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Biomedical subjects

M Goossens

Publications and source records attributed to M Goossens.

At least 163 records · Page 9Linked to original sources
PubMed1990

Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta.

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.

Adult↗
PubMed1990

Polymerase chain reaction (PCR) amplification demonstrates the absence of human T-cell lymphotrophic virus (HTLV)-I specific pol sequences in peripheral T-cell lymphomas.

HTLV-I seronegative patients in nonendemic areas have been described with T-cell proliferations the DNA of which contains specific HTLV-I viral sequences. We have looked for the presence of HTLV-I DNA sequences in 27 HTLV-I seronegative patients with peripheral T-cell lymphomas, distinct from adult T-cell leukemia (ATL), and four HTLV-I seropositive patients, three with an ATL and one with a tropical spastic paraparesis. Using HTLV-I pol specific primers, the genomic DNA from peripheral blood mononuclear cells and lymph nodes massively infiltrated by tumor cells was analyzed by the enzymatic gene amplification procedure. In contrast to the peripheral blood lymphocytes from the four HTLV-I seropositive patients, the peripheral T-cell lymphoma samples did not harbor HTLV-I pol sequences. The data show that the detection of HTLV-I nucleotide sequences by the polymerase chain reaction correlates with serologic analysis in this series.

Base Sequence↗
PubMed1990

Frequency of the cystic fibrosis delta F508 mutation in a large sample of the French population.

We have determined the frequency of the cystic fibrosis (CF) delta F508 mutation in a large sample of CF patients originating from different areas of France, including the greater Paris, Brittany, Alsace, Lorraine and Rhône-Alpes regions. A total of 422 CF chromosomes were studied, and the defect was found to account for 75% of the mutant alleles. In the course of the survey, a rare nucleotide sequence polymorphism leading to an isoleucine to valine substitution at position 506 of the CF transmembrane conductance regulator protein has been characterized in an unaffected individual. Our data enable the evaluation of the probabilities that a chromosome negative for the delta F508 mutation carriers another CF defect.

Cystic Fibrosis↗
PubMed1990

Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis.

The cystic fibrosis (CF) gene was recently identified as a gene spanning 250 kilobases (kbp) and coding for a 1480 amino acid protein, cystic fibrosis transmembrane conductance regulator (CFTR). Approximately 70% of CF mutations involve a three-base-pair deletion in CFTR exon 10, resulting in the loss of a phenylalanine at position 508 in the gene product (delta F508). In order to screen for other molecular defects, we have used a strategy based on denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR)-amplified gene segments. This method, which permits rapid detection of any sequence change in a given DNA stretch, was used successfully to analyse 61 non-delta F508 CF chromosomes from French CF patients. A study of CFTR exons 10, 11, 14a, 15 and 20 detected three mutations located in exons 14a, 15 and 20, along with several nucleotide sequence polymorphisms. These nucleotide changes were identified by direct sequencing of PCR fragments displaying altered electrophoretic behaviour, together with some of the polymorphisms and mutations previously characterized by others. The strategy presented here constitutes a valuable tool for the development of carrier testing for individuals or couples with a family history of cystic fibrosis, and will contribute to deciphering the functionally important regions of the CFTR gene.

Cystic Fibrosis↗
PubMed1990

Autotransfusion during aorto-iliac surgery.

Red blood cell (RBC) quality and function during autotransfusion with the Solcotrans system were studied. Up to 64% (mean 999.5 +/- 310 ml) of the total volume of blood lost (mean 1895 +/- 707 ml) during operation in 10 patients undergoing elective abdominal aortic surgery was salvaged. No patient received homologous blood during surgery. Haemoglobin (Hb) and Haematocrit (PCV) values decreased but within acceptable limits. No evidence of DIC was found and renal function was unaffected. Mechanical and functional damage to the RBC was minimal and erythrocyte oxygen-carrying capacity was excellent. 2,3-DPGRBC concentration and RBC reduced glutathion were normal. The device was easy to handle and technical problems were not encountered. It was accurate in salvaging blood although the need for homologous blood was not entirely eliminated since four patients received homologous blood products in the postoperative period. No adverse clinical events occurred.

Aged↗
PubMed1990

Expression of the alpha/beta and gamma/delta T-cell receptors in 57 cases of peripheral T-cell lymphomas. Identification of a subset of gamma/delta T-cell lymphomas.

Fifty-seven cases of peripheral T-cell lymphoma were studied for cell expression of the T-cell receptor (TCR) chains, using monoclonal antibodies specific for the beta chain (beta F1) of the alpha/beta TCR, and for the delta chain (anti-TCR delta-1) of the gamma/delta TCR. Three different patterns were demonstrated: in 39 cases (69%), the phenotype (CD3+beta F1+TCR delta-1-) was that of most normal T cells. A second pattern was found on six cases (10%), which were of CD3+beta F1-TCR delta-1+ phenotype, and in which DNA analysis showed a clonal rearrangement of the delta locus in the five cases studied. It is suggested that these cases are the neoplastic counterpart of the small subpopulation of normal T cells that express gamma delta receptor. It is of considerable interest that these gamma delta lymphomas had unusual clinicopathologic presentations, as one case corresponded to a lethal midline granuloma and the five others to hepatosplenic lymphomas with a sinusal/sinusoidal infiltration in spleen, marrow, and liver. The fact that the distribution of the neoplastic gamma delta cells in the splenic red pulp resembles that of normal gamma delta cells reinforces the concept of a preferential homing of gamma delta T cells to this tissue. A third pattern (CD3 +/- beta F1-TCR delta-1-) was seen in 12 cases (21%), in which, by contrast to normal post-thymic T cells, no evidence of either alpha beta or gamma delta T cell receptor was found.

Antibodies, Monoclonal↗
PubMed1990

[The amplification of nucleotide sequences by PCR and the new technics for molecular diagnosis].

The polymerase chain reaction (PCR) is a method for selective amplification of DNA or RNA segments of up to 2 kilobase pairs (kb) or more in length. Repeated cycles of enzymatic primer extension in opposite directions are performed using synthetic oligonucleotides flanking the sequences of interest and the heat-stable DNA polymerase from the archaebacterium Thermus aquaticus (Taq polymerase). The reaction is simple, fast and extremely sensitive, and the DNA or RNA content of a single cell is sufficient to detect a specific sequence. This method has proved useful in simplifying complex analytical protocols in basic and applied molecular biology.

DNA↗
PubMed1990

Frequent detection of minimal residual disease by use of the polymerase chain reaction in long-term survivors after bone marrow transplantation for chronic myeloid leukemia.

The polymerase chain reaction (PCR) allows the detection of minimal amounts of nucleic sequences and has been successfully used to test for the chronic myeloid leukemia-specific bcr/abl transcripts. We studied blood samples from 17 patients who had undergone allogeneic bone marrow transplantation for CML, using a modified polymerase chain reaction-based assay for the detection of leukemic mRNA. This nested PCR technique was found to be highly sensitive, detecting the chimeric bcr/abl transcript in 16 of 17 patients including several long-term survivors. Cytogenetic techniques failed to detect Ph mitoses. The clinical significance of the persisting bcr/abl transcript for long periods following BMT is poorly understood and remains to be elucidated by further studies.

Bone Marrow Transplantation↗
PubMed1989

Laron dwarfism and mutations of the growth hormone-receptor gene.

Laron dwarfism is associated with resistance to growth hormone (GH). To investigate its genetic basis, we used genetic linkage to test whether the disorder results from a defect in the gene for the human GH receptor. Denaturing gradient gel electrophoresis and sequencing of specific GH-receptor-gene fragments allowed us to characterize specific intragenic DNA markers in 35 control subjects of Mediterranean descent, for use in linkage studies. In two Mediterranean families in which the parents were consanguineous and some of the children had Laron dwarfism, the disease trait and DNA polymorphisms were inherited together. Moreover, an analysis of the GH-receptor-gene RNA transcripts in lymphocytes from one of these families allowed us to identify a thymidine-to-cytosine substitution that generated a serine in place of a phenylalanine at position 96 in the extracellular coding domain of the mature protein. This defect probably affects the receptor adversely and is probably responsible for the lack of plasma GH-binding activity in the patients. This mutation was not found in the GH-receptor genomic sequences of seven unrelated subjects with Laron dwarfism who belonged to different population groups. An analysis of the GH-receptor markers in these patients indicated that different gene frameworks (polymorphic sites within the single gene) were associated with the mutant alleles. We conclude that Laron dwarfism is due to abnormalities in the gene for GH receptor, which may differ from family to family.

Base Sequence↗
PubMed1989

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val).

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha-globin expression.

Amino Acid Sequence↗
PubMed1989

Regulated expression of the overlapping ubiquitous and erythroid transcription units of the human porphobilinogen deaminase (PBG-D) gene introduced into non-erythroid and erythroid cells.

The human gene coding for porphobilinogen deaminase (PBG-D) is transcribed into two distinct transcription units giving two mRNAs. These units originate from two adjacent promoters distant of 3 kilobase pairs. The upstream promoter is active in all cell types, whereas the downstream promoter is active only in erythroid cells. We have studied the expression of this gene either after introduction of the corresponding human chromosome into murine erythroid cells using somatic hybrids or after transfection into both erythroid and non-erythroid cells. Using somatic hybrids, we showed that activation of the erythroid-specific promoter of the PBG-D gene did not reduce the rate of initiation of the ubiquitous promoter. Transfection experiments in erythroid cells showed that the PBG-D erythroid transcription unit, controlled by the PBG-D erythroid promoter, was correctly transcribed and regulated. Furthermore, we found that the PBG-D erythroid promoter alone was sufficient for correct expression and regulation of a reporter gene during erythroid differentiation. When the human PBG-D gene was transfected into non-erythroid cells, only the ubiquitous promoter was active. Deletion of the ubiquitous promoter did not lead to any activation of the erythroid promoter, suggesting that its inactivity in non-erythroid cells was not due to promoter occlusion but to a strict erythroid specificity.

Ammonia-Lyases↗