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M H Stern

Publications and source records attributed to M H Stern.

At least 37 records · Page 2Linked to original sources
PubMed1995

The 8 kD product of the putative oncogene MTCP-1 is a mitochondrial protein.

An unusually small (8 kD) protein (p8MTCP-1) is coded by the putative oncogene MTCP-1 (also called c6.1B), involved in the translocation t(X;14)(q28;q11) associated with some mature T-cell proliferations. Here, we show by subcellular fractionation and by confocal microscopy that this protein is located in the mitochondria. This localization orientates toward a role of p8MTCP-1 in the mitochondrial metabolism which may be relevant for the oncogenic process.

Amino Acid Sequence↗
PubMed1994

The MTCP-1/c6.1B gene encodes for a cytoplasmic 8 kD protein overexpressed in T cell leukemia bearing a t(X;14) translocation.

The t(X;14)(q28;q11.2) translocation is associated with mature T-cell proliferations. Recently this translocation has been shown to implicate the MTCP-1/c6.1B gene on chromosome Xq28, leading to aberrant or overexpressed MTCP-1 transcripts. The potential coding role of this gene was made uncertain by the lack of a long open reading frame in its major transcripts. However, a short 204 bases open reading frame is potentially coding for a 68 amino-acid protein. Here, we show that this open reading frame sequence and the deduced product are well conserved in mouse. A 8 kD protein (p8), which corresponds to the predicted molecular weight was revealed in transient transfectants and in cell lines by Western blotting, using a rabbit antiserum. This product was absent in lymphoblastoid cell lines with deletions of the MTCP-1/c6.1B locus. A dramatic overexpression of p8 was found in leukemic cells from a patient with a t(X;14). This small protein was localized in the cytoplasm by immunofluorescence. In conclusion, MTCP-1 encodes for a cytoplasmic 8 kD product. Its potential role in leukemogenesis is supported by its overexpression in leukemia with t(X;14), but its function remains unknown.

Amino Acid Sequence↗
PubMed1993

MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations.

T-cell lymphoproliferative diseases are often associated with recurrent chromosomal translocations involving T cell receptor genes (TCR) and genes that are thought to play a role in the pathogenesis of these diseases. Whereas numerous such genes have already been identified in acute T cell leukemias, no candidate gene has yet been identified to play a role in the heterogeneous group of T cell proliferations with a mature phenotype. We here report the molecular cloning of two examples of the rare but recurrent t(X;14) translocation. The first translocation was associated with a benign clonal proliferation in an ataxia telangiectasia patient and the second with a T cell prolymphocytic leukemia. Both translocations implicated the TCR alpha/delta locus and a common breakpoint region on chromosome Xq28. A previously unidentified gene, abnormally transcribed in both T cell proliferations, was characterized in the immediate proximity of the breakpoints. This Xq28 gene has no homology with known sequences, uses a complex alternative splicing pattern and demonstrates two short open reading frames. This gene, named MTCP-1 (Mature T Cell Proliferation-1) is the first candidate gene potentially involved in the leukemogenic process of mature T cell proliferations.

Alternative Splicing↗
PubMed1993

Ataxia telangiectasia: a model for T-cell leukemogenesis.

Ataxia telangiectasia is a complex genetic disease which includes a high risk to develop lymphoid malignancies. In approximately 10% of the patients, clonal translocations are observed in large T lymphocytes populations, with generally no consequences for the patient. Cytological and biological studies of these cell populations have shown striking similarities with T-cell prolymphocytic leukemia. Clonal chromosomal aberrations are constituted by the translocation of one TCR gene to either the 14q32.1 band or the Xq28 band. Whereas no gene candidate is yet identified on the 14q32.1 region, we have recently identified a new gene on Xq28 that may play a role in leukemogenesis.

Ataxia Telangiectasia↗
PubMed1990

Hybrid T cell receptor genes formed by interlocus recombination in normal and ataxia-telangiectasis lymphocytes.

In this paper, using polymerase chain reaction (PCR), we demonstrated the occurrence of hybrid genes formed by interlocus recombination between T cell receptor gamma (TCR-gamma) variable (V) regions and TCR-beta joining (J) regions in the peripheral blood lymphocytes (PBL) from normal individuals and patients with ataxia-telangiectasia (AT). Sequence analysis of the PCR-derived hybrid genes confirmed that site-specific V gamma-J beta recombination had occurred and showed that 10 of 23 genomic hybrid genes maintained a correct open reading frame. By dilution analysis, the frequency of these hybrid genes was 8 +/- 1/10(5) cells in normal PBL and 587 +/- 195/10(5) cells in AT PBL. These frequencies and the approximately 70-fold difference between the normal and AT samples are consistent with previous cytogenetic data examining the occurrence of an inversion of chromosome 7 in normal and AT PBL. We also demonstrated expression of these hybrid genes by PCR analysis of first-strand cDNA prepared from both normal and AT PBL. Sequence analysis of the PCR-amplified transcripts showed that, in contrast to the genomic hybrid genes, 19 of 22 expressed genes maintained a correct open reading frame at the V-J junction and correctly spliced the hybrid V-J exon to a TCR-beta constant region, thus allowing translation into a potentially functional hybrid TCR protein. Another type of hybrid TCR transcript was found in a which a rearranged TCR-gamma V-J exon was correctly spliced to a TCR-beta constant region. This form of hybrid gene may be formed by trans-splicing. These hybrid TCR genes may serve to increase the repertoire of the immune response. In addition, studies of their mechanism of formation and its misregulation in AT may provide insight into the nature of the chromosomal instability syndrome associated with AT. The mechanism underlying hybrid gene formation may be analogous to the mechanism underlying rearrangements between putative growth-affecting genes and the antigen receptor loci, which are associated with AT lymphocyte clones and lymphoid malignancies.

Ataxia Telangiectasia↗
PubMed1990

Analysis of positive cultures from endodontically treated teeth: a retrospective study.

A study of 12,150 endodontically treated teeth from 11,797 patients in a private patient setup revealed an incidence of 10.2% positive cultures obtained just before obturation of the root canal. Streptococcal predominance was reflected by a presence of nearly 60% in the pure culture and nearly 98% in the mixed cultures. No significant changes in microbial predominance or bacterial sensitivities were detected over the 7-year period of study. Ampicillin, cephalothin, erythromycin, and penicillin were the most effective antibiotics against the viridans streptococci, the most prevalent organism in the infected teeth.

Adolescent↗
PubMed1990

Mapping of human chromosome 22 by in situ hybridization.

The second smallest chromosome of the human karyotype, i.e., chromosome 22, is involved in many congenital or acquired structural aberrations. This variety can be taken advantage of to determine the exact linear order, from centromere to telomere, of cloned probes and chromosomal breakpoints. Eleven probes were localized with respect to breakpoints of 11 der(22) of independent cell lines using in situ hybridization on metaphasic spreads. The deduced order of the tested probes and that of the breakpoints are in complete agreement with the published genetic map and the karyotypic analysis, respectively. This approach enables a correlation of the genetic map with the chromosomal banding.

Cell Line↗
PubMed1989

Inversion of chromosome 7 in ataxia telangiectasia is generated by a rearrangement between T-cell receptor beta and T-cell receptor gamma genes.

Specific and recurrent chromosomal rearrangements are often observed in the karyotypes of phytohemagglutinin-stimulated lymphocytes. The percentage of cells demonstrating these rearrangements is dramatically increased in the genetic disease ataxia telangiectasia. Inversion of chromosome 7 represents approximately half of the chromosomal rearrangements in this disease. Because the chromosomal locations of the inv(7) breakpoints coincide precisely with those of the T-cell antigen receptor (TCR) beta and gamma genes, it has been hypothesized that this rearrangement may occur by recombination between those two loci. Here, we present direct evidence that inversion of chromosome 7 in ataxia telangiectasia is generated by site-specific recombination between a TCR gamma variable segment and a TCR beta joining segment.

Ataxia Telangiectasia↗
PubMed1989

T-cell nonmalignant clonal proliferation in ataxia telangiectasia: a cytological, immunological, and molecular characterization.

Cytogenetically abnormal T-cell nonmalignant clones are a characteristic feature of ataxia telangiectasia (AT). Here, we study a t(14;14) clone from a patient with AT, and provide a cytological, immunological, and molecular characterization. This cellular population is clonal at the molecular level, but is phenotypically heterogeneous, with CD4+CD8+ and CD4-CD8+ cells. Although these cells do not divide in the peripheral blood, a majority of them are found in G1 phase and express the membrane antigen 4F2, a very early marker of activation. Many similarities are found between this nonmalignant AT clone and T-cell prolymphocytic leukemia at the morphologic, cytogenetic, and immunologic levels, despite the different clinical courses associated with these proliferations. We hypothesize that the t(14;14) translocation is linked to the abnormal morphology and immunophenotype of the AT clone cells, but that this translocation confers only a preactivated state to the cells. A complete malignant transformation would then be due to secondary events.

Adolescent↗
PubMed1988

Molecular characterization of different ataxia telangiectasia T-cell clones. I. A common breakpoint at the 14q11.2 band splits the T-cell receptor alpha-chain gene.

Using in situ chromosomal hybridization we have mapped the gene for the T-cell receptor alpha-chain in three different non-malignant T-cell clones occurring in ataxia telangiectasia. The constant region was translocated in each of the three clones. The variable region remained in its original position in two cases and was deleted in one clone which lost the derivative chromosome 14. We have therefore demonstrated that the T-cell receptor alpha-gene is split in at least two of these translocations. To our knowledge, this is the first direct evidence of the involvement of a gene from the immunoglobulin superfamily in chromosomal rearrangements in ataxia telangiectasia.

Ataxia Telangiectasia↗
PubMed1988

Molecular characterization of ataxia telangiectasia T cell clones. II. The clonal inv(14) in ataxia telangiectasia differs from the inv(14) in T cell lymphoma.

We compared inversions of chromosome 14 in an ataxia telangiectasia clone and in a malignant T cell line (SUP-T1). The R-banding chromosome analysis showed a clear difference between the distal breakpoint of the two inversions. Fine mapping of the distal breakpoint in the ataxia telangiectasia inv(14) was performed by in situ hybridization. We conclude that this breakpoint is centromeric to the immunoglobulin heavy chain locus and to the D14S1 anonymous locus. Our results favor the existence of an unknown oncogene in band 14q32.1.

Ataxia Telangiectasia↗
PubMed1982

Isolation and characterization of inflammatory cells from the human periapical granuloma.

Twelve histologically-confirmed periapical granulomas were evaluated by conventional immunologic rosette assays for the presence of T-lymphocytes and complement receptor-bearing lymphocytes. A technique for dispersing the granuloma cells into suspensions was adopted to facilitate performance of the assays which were not applicable to tissue sections. Differential cell counts by an acridine orange vital dye method disclosed that the cell suspensions contained 30% macrophages, 44% lymphocytes, 15% plasma cells, and 12% neutrophils. Complement receptor-bearing cells comprised 17.9%, and T cells comprised 34.5% of the unseparated inflammatory cells. This study provides the first direct evidence of a predominance of thymic-derived lymphocytes in the lymphocyte compartment of the periapical granuloma. Analysis of the data shows that cell-mediated immunity most likely plays a role in the pathogenesis of the periapical granuloma.

Cell Count↗