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Biomedical subjects

M Fellous

Publications and source records attributed to M Fellous.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Prenatal identification of a Y-chromosome deletion by Y-specific single copy DNA probes.

A sex chromosome deletion was identified in the course of prenatal diagnosis for maternal age. Ultrasound pictures revealed male fetal sex and a comparison with the father's Y chromosome suggested that the altered chromosome might be a de novo deletion of the Y chromosome. DNA hybridization with five human Y-specific probes shows that, among the Y-specific sequences recognized by the probes, only two of them are absent. The normal infant, at birth, was mosaic 46, XYq-/46,XY.

Adult↗
PubMedDate not supplied

Surface markers on mouse cells transformed after exposure to HeLa chromosomes are Mycoplasma membrane proteins.

Antisera were raised against HeLa cells and mouse cells transformed after exposure to HeLa chromosomes (ME-ch.HeLa). The antisera were positive in indirect immunofluorescence assays on both HeLa and ME-ch.HeLa cells, but were negative on normal mouse cells. Immunoprecipitation of 125I-labelled cell extracts showed that Me-ch.HeLa cells contain at their surface 3 proteins of apparent molecular weights of 185,000, 105,000 and 45,000 daltons, which were also present on the surface of our HeLa cells but not on other mouse cell lines tested. However, further study has shown that these proteins are not normal constituents of HeLa plasma membranes but are in fact surface proteins of Mycoplasma orale.

Animals↗
PubMedDate not supplied

The recombinant human interferon-gamma receptor is fully functional in a human x murine hybrid containing human chromosome 21.

It has previously been shown that stimulation of class I MHC antigen expression by human interferon gamma (Hu-IFN gamma) depends on the presence of both human chromosomes 6 and 21. Even although the presence of human chromosome 6 results in normal expression of the IFN gamma receptor on the cell surface, chromosome 21 is required for this biological response. Here, we transfected the cDNA encoding the Hu-IFN gamma receptor into a mouse cell line, L(tk-), and into a mouse x human hybrid, GM08, containing the human chromosome 21 as the only human genetic material. Two clones, L-gamma R.8 and GM08-gamma R.9, were tested for different biological responses to Hu-IFN gamma. Only the hybrid containing the human chromosome 21 (GM08-gamma R.9) exhibited a biological response when assayed for the stimulation of murine class I MHC antigen expression by Hu-IFN gamma. Moreover, transcriptional induction of 2'-5'-oligoadenylate synthetase and 1-8 genes, as well as antiviral protection, were observed only in the GM08-gamma R.9 transfectants. These results show that human chromosome 21 encodes a factor which mediates different biological activities of Hu-IFN gamma.

Blotting, Northern↗
PubMedDate not supplied

Human cells allosensitized in vitro release soluble suppressor factors: presence of at least two distinct factors.

Human cells allosensitized in vitro release suppressor "factors" (SF) capable of inhibiting a primary mixed lymphocyte reaction (MLR). Preincubation experiments with SF of either responders or stimulators in MLR suggested the presence of at least two distinct suppressor activities: one called SFR, acting on certain responders including the SF producer; the other called SFNR, acting on stimulators in all MLR. These activities can be separated using sorbents composed of monoclonal anti-HLA-DR antibodies on the one hand and mouse or rabbit IgG on the other hand. SFR is found in the effluent and SFNR in the eluate of these sorbents. The SFNR-binding properties are shared by a murine suppressor factor called immunoglobulin-binding factor or IBF. Moreover SFNR, like IBF, is capable of suppressing a secondary in vitro IgG response through the species barrier.

Animals↗
PubMedDate not supplied

Qualitative differences in effects of recombinant alpha-, beta- and gamma-interferons on human peripheral blood leukocytes in vitro.

The in vitro effects of bacteria-produced human interferons alpha 2, beta and gamma on several properties of peripheral blood leukocytes from different healthy donors were compared. Treatment with HuIFN-alpha 2 or HuIFN-beta resulted in inhibition of the proliferative response to phytohaemagglutinin and in closely parallel induction of 2'-5'-oligoadenylate synthetase activity. In contrast, HuIFN-gamma had no significant effect on these two activities. However, all three HuIFN were able to enhance natural killer cell cytotoxicity and the expression of HLA-DR surface antigens, with only quantitative variations from donor to donor. Similar results were observed with glycosylated recombinant hamster-cell-derived HuIFN-gamma and with natural HuIFN-gamma. These data demonstrate qualitative differences in the effects of HuIFN-gamma compared to those of HuIFN-alpha 2 or -beta on cells of the immune system.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

Human XX males with Y single-copy DNA fragments.

In humans, XX maleness is the best known example of a sex reversal syndrome occurring with an incidence of one XX male among approximately 20,000 to 30,000 newborn boys. The karyotypes of the majority of these individuals are apparently normal, with respect to the numbers and structure of the chromosomes, but is in contradiction with the phenotypic sex which they display. XX maleness may be either a non Y-related mechanism triggered by a mutation on another chromosome or could be the result of the expression of some cytogenetically undetectable Y chromosome material present in the genome of such individuals. Recently, a number of human Y-specific single copy probes have been isolated. In this study, using several of these Y-specific probes we definitively demonstrate the presence of Y-chromosomal material in the genome of some 46,XX human males. These XX males carry only a fraction of the human Y chromosome. In the three positive cases reported here, presence of inclusive overlapping chromosomal fragments has been detected, implying a genetic heterogeneity of these patients.

DNA↗
PubMedDate not supplied

Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene.

The expression of class I transplantation antigens encoded in the major histocompatibility complex (H-2 in mouse, HLA in man) can be induced by alpha-, beta- and gamma-interferons. Both transcriptional and post-transcriptional mechanisms have been postulated. Recently, a common sequence has been found in the promoter region of several human genes responsive to IFN-alpha. The promoters of H-2Kb and several other mouse class I genes contain a similar interferon response sequence. We show here, in a transient assay, that the H-2Kb promoter can be induced by all three types of interferon and that the interferon response sequence is necessary for induction to occur. However, the response sequence is active only when associated with a functional enhancer sequence which we have recently identified in the promoter of H-2Kb and other class I genes. The combination of these two sequences can render a heterologous promoter responsive to interferon, irrespective of its orientation relative to the cap site.

Animals↗
PubMedDate not supplied

Genetic evidence that ZFY is not the testis-determining factor.

In mammals, the testis determining gene (TDF), present on the Y chromosome, induces the undifferentiated gonads to form testes. The position of TDF on the human Y chromosome has been defined by analysing the genomes of XX males and XY females, generated by abnormal genetic exchange between the X and Y chromosomes in male meiosis. In this way TDF has been localized close to the pseudoautosomal region shared by the sex chromosomes, in the distal Y-specific region. A recently cloned human gene, ZFY, has many features indicating that it is TDF. For example, ZFY encodes a protein with many features of a transcription factor including a domain with multiple 'zinc-finger' motifs. Less consistent with ZFY being TDF, however, is the presence of a very similar gene, ZFX, on the X chromosome, and the presence of a sequence related to ZFY on autosomes in marsupials. We now report on analysis of XX males lacking ZFY. In these individuals, the male phenotype could be explained by a mutation in a gene 'downstream' of ZFY in the sex-determining hierarchy; but in that case there should be no exchange of material between the X and Y chromosomes. We find on the contrary that in 4 XX males lacking ZFY, there is exchange of Y-specific sequences next to the pseudoautosomal boundary, redefining the region in which TDF must lie.

Blotting, Southern↗
PubMedDate not supplied

Influence of recombinant interleukin-2 and alpha- and gamma-interferons on the induction of novel class I antigens.

Previous results obtained in our laboratory showed that novel class I antigens, closely related to HLA-A (TM antigen related to HLA-A9 and GO antigen related to HLA-A24), were expressed on activated HLA-A9 or HLA-A24 peripheral blood lymphocytes (PBL), whatever activation factor was used [mitogenic stimulation (PHA, PWM, Con A), EBV transformation or alloactivation], but not on resting T and B lymphocytes. These antigens were also expressed on HLA-A9 or HLA-A24 common acute lymphoblastic leukaemias (cALL) and some 'immature' chronic lymphocytic leukaemias (B-CLL), but not in hairy cell leukaemias (HCL), most of the B-CLL, acute myeloblastic leukaemias (AML) and acute myelomonoblastic leukaemias (AMoL). In order to investigate the regulation mechanisms of these novel class I antigens, PBL and different leukaemic cell types were treated in vitro with recombinant IL-2 (rIL-2) and alpha and gamma-interferon (rIFN). Our results showed that without previous activation, but after culture with rIL-2, TM and GO antigens could be induced in HLA-A9 or HLA-A24 PBL and enhanced in HLA-A9 or HLA-A24 B-CLL cases, whereas no expression was found in HLA-A9 or HLA-A24 HCL, T-ALL, AML or AMoL. After culture with rINFs, the expression of TM and GO antigens could be induced on HLA-A9 PBL and all HLA-A9 leukaemic cell varieties. Our results support the hypothesis that the expression of class I antigens is induced at an early stage of the cell cycle.

Cell Cycle↗
PubMedDate not supplied

Ullrich-Turner syndrome: relevance of searching for Y chromosome fragments.

Forty consecutive patients with Ullrich-Turner syndrome (UTS) were followed-up and investigated for the presence of Y chromosome fragments in their genomes. We used the polymerase chain reaction (PCR) to detect SRY (sex-determining region on the Y chromosome) and the sequence-tagged sites (STS) sY57, sY59, sY85, sY94, sY124 and sY157--which correspond to regions 3C (sY57 and 59), 5C, 5G, 5P, and 6F, respectively, of the Y chromosome--searching for Y fragments that could bear the putative locus (loci) for gonadoblastoma (GBY). It has been shown that the presence of GBY greatly increases the risk of dysgenic gonads to undergo malignant transformation. Among our 40 patients, we found Y-derived sequences--including SRY and the region spanning from sY57 to sY94--in two. These two patients had a marker chromosome detected by conventional cytogenetic analysis (45,X/46,X + mar). Their gonads were excised and found to be streaks. In one of the patients, we found foci of primitive sex cords (amidst the gonadal stroma), oviducts and Wolffian remnants. Fluorescence in situ hybridization (FISH) did not show Y chromosome material in her gonad-derived fibroblasts. The other girl had hyperplastic Leydig cells in the gonadal stroma, oviducts and Wolffian remnants, with signs of epididymal differentiation. PCR assays performed on DNA extracted from paraffin-embedded gonadal tissue were negative for SRY sequences in both patients. These findings show that all UTS patients should be examined for Y chromosome material, and that positive cases should have their dysgenic gonads excised due to the high risk of malignancy.

Base Sequence↗
PubMedDate not supplied

Persistence of Müllerian remnants in complete androgen insensitivity syndrome.

One of the unusual findings in androgen insensitivity syndrome (AIS) is the persistence of Mullerian derivatives. Several hypotheses have been advanced to explain such persistence: the coincidental occurrence of mutations affecting the androgen receptor (AR) and the synthesis and/or action of anti-Müllerian hormone (AMH); the loss of AMH paracrine action due to early testicular descent; the exposure to drugs such as diethylstilbestrol. We describe a patient with complete AIS for whom surgical and laboratory findings rule out all these hypotheses. She has a missense mutation on the AR gene but no mutations were detected on the genes coding for AMH and AMH receptor. The gonads were found very close to the Mullerian structures (enough to exert a paracrine action), gonadal tissue stained positively for AMH, and yet Mullerian derivatives were present and well developed. These findings indicate the possibility of interactions between the androgen receptor and AMH action.

Adolescent↗
PubMedDate not supplied

Hermaphroditism pathology.

Hermaphroditism is a more general term for the discrepancy between the phenotype and the genotype of sex development than sexual ambiguity, which refers mainly to external genitalia anomalies. Hermaphroditism is studied on an historical and pathogenetical perspective. Short embryological summaries are integrated. The defects of sexual differentiation due to a hormonal deficiency are first studied: androgen insensitivity, steroid 5 alpha-reductase 2 deficiency, defects of testosterone synthesis, persistent mullerian ducts syndrome. Sexual determinism deficiencies come after: Turner syndrome, XX males, pure gonadal dysgenesis, and true hermaphroditism, mixed gonadal dysgenesis, Drash and Frasier syndrome. Tumors of dysgenetic gonads followed. Mixed tumors developed in dysgenetic gonads are gonadoblastoma and dysgerminoma. Sex cord tumors are androgen insensitivity associated tumors, Leydig cells tumors and adrenal cell inclusion tumors. New perspectives open by sex reversion genes are open.

Androgens↗
PubMedDate not supplied

[Presence of 2 different epitopes on the human beta 2-microglobulin defined by monoclonal antibodies].

Two monoclonal antibodies recognizing monomorphic determinants on class I antigens of MHC were characterized. They were shown to recognize beta 2m by cytotoxicity inhibition studies. The epitopes recognized were different, as assayed by cross-inhibition and phylogenetical studies. One antibody recognized free as well as HLA-associated beta 2m. The other reacted with a conformational epitope which was well conserved during evolution.

Animals↗