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Biomedical subjects

R Hyman

Publications and source records attributed to R Hyman.

At least 73 records · Page 4Linked to original sources
PubMed1987

A mutant lymphoma cell line with a defective Thy-1 glycoprotein gene.

We characterized a mutant T-cell lymphoma line selected for the inability to express the Thy-1 glycoprotein. This cell line is a member of the D complementation class of Thy-1- somatic cell mutants, and it lacks detectable cell-surface Thy-1.1 glycoprotein and detectable cytoplasmic Thy-1 mRNA. Southern blot analysis using a number of probes isolated from the cloned Thy-1.2 gene demonstrated that, in the mutant, one copy of the Thy-1 gene is absent from the genome and the other has undergone rearrangement. This rearrangement results from a deletion of the 5' portion of the gene removing the first two alternate exons and promoters and a portion of the second intron. The deletion breakpoint within the mutant Thy-1 gene was localized to within 400 nucleotides by Southern blot analysis. The breakpoint is near two classes of mouse repetitive elements-a mouse B1-family repetitive element and a simple repetitive sequence-suggesting a mechanism of rearrangement leading to the mutation. Southern blot analysis demonstrated that two closely linked molecular markers on chromosome 9 are unaltered, demonstrating that the deletion in this mutant cell line is subchromosomal.

Animals↗
PubMed1986

Anchoring of membrane proteins via phosphatidylinositol is deficient in two classes of Thy-1 negative mutant lymphoma cells.

Recent evidence shows that mature Thy-1 glycoprotein lacks amino acids 113-143 predicted from the cDNA sequence and is anchored to the plasma membrane by a phosphatidylinositol-containing glycolipid attached to amino acid 112. Previously characterized Thy-1-deficient mutant lymphoma lines of complementation classes A and E were analysed. They make detergent binding Thy-1 precursors but, in contrast to wild-type, the detergent binding moiety cannot be removed by phospholipase C. Moreover, tryptophan which only occurs at position 124 is incorporated into mutant but not parental Thy-1. This suggests that the mutants make a Thy-1 precursor of 143 amino acids but fail to replace its C-terminal end by a glycolipid anchor.

Animals↗
PubMed1986

A mutational hot-spot within an intron of the mouse beta 2-microglobulin gene.

beta 2-Microglobulin is the smaller, relatively non-polymorphic chain of class I major histocompatibility complex proteins. We have previously described a mutant mouse cell line which had been selected for loss of the class I thymus leukemia (TL) antigen and had concomitantly lost surface expression of H-2k antigens. Expression of class I antigens on the cell surface was restored by fusion to an antigenically distinct mouse lymphoma line, and the defect in the mutant was shown to be the loss of a functional beta 2-microglobulin gene. We now describe three additional mutants with the same phenotype, all selected for loss of TL but after different types of mutagenesis. All of these mutants have genomic rearrangements resulting in the absence of a functional beta 2-microglobulin gene. These data provide strong evidence for the requirement of beta 2-microglobulin for cell surface expression of the heavy chain of class I major histocompatibility complex proteins. We further show that the defects in at least one beta 2-microglobulin gene in each mutant cell line map to the same small DNA segment within the first intron. The breakpoints of these mutations define a hypermutable site within the mouse beta 2-microglobulin gene.

Animals↗
PubMed1986

Autocrine growth and progression of murine X-ray-induced T cell lymphomas.

Primary tumors of X-ray-induced murine T cell lymphomas comprise autocrine, growth factor-dependent cells. We have grown cell lines from primary X-ray-induced thymic lymphomas (PXTLs) under conditions which minimize the progression of the cells from factor dependence to factor independence. All (22) PXTL lines grown secrete a growth factor which supports their own growth and which we will call lymphoma growth factor LGF. LGF-dependent cells are non-tumorigenic or poorly tumorigenic, do not clone in soft agar, have no detectable rearrangements in the c-myc or Pim-1 region and possess near diploid or pseudodiploid karyotypes without evidence for trisomy of chromosomes nos. 15 or 17. PXTL-secreted LGF has no interleukin 1, 2, or 3 activity nor do LGF-secreting cells synthesize detectable IL-1, -2, or -3 mRNA. LGF contains no detectable interferon or GM-CSF activity in specific bioassays. Purified EGF, TGF beta, and interleukin preparations are inactive on LGF-dependent PXTL cells. Thus LGF appears to be a new growth factor that is required for the proliferation of non-progressed T lymphoma cells. Upon progression PXTL cells become growth factor independent, are highly tumorigenic in vivo, clone in soft agar, and assume a near triploid karyotype containing numerous chromosomal aberrations. Thus in X-ray-induced lymphomagenesis an autocrine, LGF-dependent phase precedes the progressed phase characterized by rearrangements in the myc and/or Pim-1 regions as well as by many chromosomal aberrations visible in the karyotype.

Animals↗
PubMed1986

Simultaneous occurrence of herniated disc and mesothelial cyst in a 16-year-old male.

The unusual, simultaneous occurrence of both a herniated disc and an intraspinal mesothelial cyst in an adolescent is reported. The patient was a 16-year-old white male who presented with sciatic pain in his left lower extremity. Myelography revealed evidence of a left L4-5 discal herniation, and a L5-S3 midline sacral lesion that proved to be a mesothelial cyst.

Adolescent↗
PubMed1986

A Thy-1- mutant defining a gene acting in trans position to regulate cell-surface Thy-1 glycoprotein expression and Thy-1 messenger RNA content.

The Thy-1 glycoprotein is a differentiation antigen which exhibits tissue-specific regulation. A mutant of a Thy-1.1+ T-cell lymphoma has been isolated which does not express Thy-1 glycoprotein on the cell surface and does not accumulate Thy-1 mRNA in the cytoplasm. Hybrids between the mutant and a Thy-1.2+ T-cell lymphoma express 20-30-fold lower levels of Thy-1 glycoprotein on their cell surface compared to wild-type T-cell lymphomas, and they have correspondingly low levels of cytoplasmic Thy-1 mRNA. A revertant of one hybrid was isolated which expressed wild-type levels of both Thy-1 alleles on its surface and contained correspondingly increased levels of Thy-1 mRNA. A Thy-1+ revertant of the Thy-1- mutant was isolated by cell sorting. A second generation Thy-1- mutant could be isolated from this revertant which also did not accumulate Thy-1 mRNA and which behaved in a way similar to the first generation mutant when hybridized to a Thy-1.2+ lymphoma. No changes in the structure or copy number of the Thy-1 structural gene could be detected in this series of mutants and revertants. These properties are consistent with a mutation in one (or more) gene(s) which acts in trans position to regulate Thy-1 glycoprotein expression.

Animals↗
PubMed1986

Identification and characterization of the human Pgp-1 glycoprotein.

Two monoclonal antibodies have been raised against human Pgp-1 by the immunization of mice with human fibroblasts. The human molecule, like the previously identified mouse counterpart, is an abundant membrane protein (Mr approximately 95 000) with a broad tissue distribution. Pgp-1 is phosphorylated, and phosphoamino acid analysis demonstrates that this occurs exclusively on serine residues. A major difference between the mouse and the human is that 50-60% of human thymocytes are Pgp-1+ compared to 5-10% of mouse thymocytes at an equivalent stage in development. Immunofluorescence studies of cryostat sections showed that the majority of human medullary thymocytes are strongly stained with Pgp-1-specific antibody, whereas the expression of Pgp-1 on cortical thymocytes is much more heterogeneous.

Age Factors↗
PubMed1986

Progenitor cells in the thymus: most thymus-homing progenitor cells in the adult mouse thymus bear Pgp-1 glycoprotein but not interleukin-2 receptor on their cell surface.

Pgp-1-positive and interleukin-2-receptor (IL-2R)-positive cells are both minor (less than 5%) subpopulations within the adult thymus. A thymocyte population enriched for these two cell types, obtained by killing the bulk of thymocytes with anti-Thy-1 antibody and complement, contains thymus-homing progenitor cells which can transiently repopulate the thymus of irradiated recipients. Using two-color immunofluorescence, we demonstrate that the Pgp-1+ and IL-2R+ cells present in this enriched population represent largely nonoverlapping subsets, although some cells do express both markers. We also show by depletion of these two cell types that the bulk of the thymus-homing progenitors present in this enriched population are found in the Pgp-1+ population, and not in the IL-2R+ population. We discuss the relationship between the thymus-homing progenitors in this depleted thymus subpopulation and the thymus-homing progenitors present in the thymus as a whole.

Animals↗
PubMed1986

Non-tumoural aqueduct stenosis and normal pressure hydrocephalus in the elderly.

From 1981 to 1985 a prospective study on normal pressure hydrocephalus was performed. One of the aims of this study was to determine the site of CSF obstruction. Among 17 consecutive patients with a tentative diagnosis of normal pressure hydrocephalus, nine appeared to have non-communicating hydrocephalus most probably due to primary non-tumoural aqueduct stenosis. This unexpected finding provides evidence that non-tumoural aqueduct stenosis is a frequent cause of normal pressure hydrocephalus in older patients. Some clinical, aetiological and therapeutic aspects in this particular subgroup are discussed.

Aged↗
PubMed1986

The effect of nuclear magnetic resonance imaging on metallic middle ear prostheses.

Nuclear magnetic resonance imaging, a relatively new diagnostic instrument, is a noninvasive imaging method which, among its many advantages, uses no ionizing radiation. There are a few limitations and contraindications to its use. There may be displacement of intracerebral aneurysm clips and metallic implants, and cardiac pacemakers can be disabled because of the high magnetic field created by this device. We studied the effects of a magnetic field on metallic middle ear prosthetics and concluded that nuclear magnetic resonance imaging should offer no risks to hearing or otologic function in patients with nonferromagnetic metallic middle ear prosthetics. Nuclear magnetic resonance imaging is contraindicated in patients with cochlear implants.

Ear, Middle↗
PubMed1985

Evidence that the Pgp-1 glycoprotein is expressed on thymus-homing progenitor cells of the thymus.

The Pgp-1 glycoprotein is found on the bone marrow prothymocyte; however, only a few percent of cells within the normal thymus express significant quantities of Pgp-1 glycoprotein. One hypothesis is that some or all of these Pgp-1+ thymocytes represent thymocyte progenitors or the immediate descendents of the bone marrow-derived prothymocyte. A cell present in the thymus which is able to home back to the thymus and to transiently repopulate it represents one class of thymocyte progenitor. Thymocyte populations enriched in this thymus-homing progenitor are enriched in Pgp-1+ cells. Treatment of these enriched populations with anti-Pgp-1 antibody inhibits activity of the thymus-homing progenitor. These results are consistent with the hypothesis that the thymus-homing progenitor bears Pgp-1 on its surface.

Animals↗
PubMed1985

The Pgp-1 antigen is expressed on early fetal thymocytes.

The Pgp-1 glycoprotein is expressed on the bone marrow prothymocyte and on a class of intrathymic progenitor cells in the adult animal. Only 5% of adult thymocytes are strongly Pgp-1+. When fetal thymocytes of day 13-14 of gestation are examined by flow cytometric analysis, 80-90% of thymocytes are Pgp-1+, while the bulk of thymocytes are Thy-1-. By day 15-16, the percentage of Pgp-1+ cells begins to fall while nearly all cells become Thy-1+. Two-color immunofluorescence indicates that many Pgp-1+ cells are Thy-1+. The percentage of Pgp-1+ cells continues to fall over the next several days, reaching adult levels by day 19. These observations are consistent with the interpretation that at least some classes of thymocyte progenitors are Pgp-1+.

Animals↗
PubMed1985

Stable expression of the mouse lymphocyte T200 antigen in L-cells after transfection with lymphoma DNA.

L-cells, which normally do not express the mouse lymphocyte T200 antigen, were transfected with DNA from the mouse T-cell lymphoma, BW5147, and a T200+ L-cell line isolated. The detection and enrichment of T200+ L-cells from a pool of transfectants was accomplished using monoclonal anti-T200 antibody and fluorescence-activated cell sorting. A subclone has been selected that is stable for expression of T200. The T200 molecules expressed by BW5147 and the T200+ L-cell are similar in size, around 190 Kd, compared to the 220-Kd B-cell form of T200. The BW5147 T200 molecule is 3000 daltons larger than the molecule expressed by the transfected L-cell, a size difference due to glycosylation moieties, since treatment of the molecules with Endoglycosidase F or treatment of cells with tunicamycin yields T200 molecules of the same size from the 2 cell sources. In comparison, the B-cell form of T200 retains a size difference of 25,000 daltons from the T-cell form after these treatments. Monoclonal antibodies specific for the B-cell form of T200 do not recognize the T200+ L-cell, providing further evidence that the T-cell form of T200 is expressed by the transfected L-cell.

Animals↗
PubMed1985

Analysis of commitment of human leukemia HL-60 cells to terminal granulocytic maturation.

Analysis of commitment of human promyelocytic leukemia HL-60 cells to terminal granulocytic maturation induced by dimethyl sulfoxide (DMSO) or retinoic acid (RA) was accomplished using biochemical measurements and a plasma clot clonal assay system that permits a high plating efficiency of 40 to 60%. Commitment to granulocytic maturation occurs very rapidly. When cells are exposed to these inducers for only 8 to 18 h, an interval much shorter than a single generation time, and are then subcultured in inducer-free plasma clots, they demonstrate a decrease in proliferative capacity and form colonies composed of mature nitroblue tetrazolium (NBT)-positive cells along with occasional colonies containing both NBT-positive and NBT-negative cells; in both types of colony, the NBT-positive cells are widely dispersed. Undifferentiated HL-60 cells give rise to compact NBT-negative colonies of large size without cell migration. HL-60 cell differentiation induced by either DMSO or RA is associated with a progressive decline in both DNA and RNA synthesis; this includes transcriptional inactivation of ribosomal DNA sequences. In contrast to DMSO, which induces development primarily of metamyelocytes, RA treatment leads to the accumulation of more mature band and segmented neutrophils; sequential exposure of cells pretreated with DMSO to RA alone fails to cause rapid appearance of segmented neutrophils. From these studies, we conclude that HL-60 cells become very rapidly committed to terminal maturation and that DMSO and RA appear to induce granulocytic maturation via two different mechanisms.

Cell Differentiation↗
PubMed1984

Regulation of Thy-1 and Pgp-1 glycoproteins in hybrids between T-cell lymphomas and Abelson-leukemia-virus-induced lymphomas.

Most cells in the normal adult mouse thymus express Thy-1 glycoprotein but do not express Pgp-1 glycoprotein. In contrast, cells of the mouse B-cell lineage are Thy-1 negative and Pgp-1 positive. Somatic cell hybrids between pseudodiploid Thy-1+, Pgp-1- T-cell lymphomas and pseudotetraploid Thy-1-, Pgp-1+ Abelson-leukemia-virus-induced cell lines do not express detectable cell-surface Thy-1 but show activation of the T-cell Pgp-1 glycoprotein. Hybrids between pseudodiploid lines, in contrast, show extinction of Pgp-1. Thy-1+ or Pgp-1+ revertants were isolated by cell sorting from hybrids in which extinction occurred, demonstrating that all genes required for expression of these cell-surface antigens were present in antigen-negative hybrids. Thy-1- hybrids did not contain detectable cytoplasmic Thy-1 messenger RNA, while Thy-1 message could be detected in parental lines and Thy-1+ revertants. No obvious rearrangements of the Thy-1 structural genes could be demonstrated in Thy-1- hybrids and their Thy-1+ revertants, nor could rearrangements be demonstrated when parental cells and Thy-1- hybrids were compared. These results are consistent with the idea that diffusible gene products regulate both Thy-1 and Pgp-1 expression in these hybrids. These products act in a gene dosage-dependent manner in somatic cell hybrids. Regulation of Thy-1 is at the level of either messenger RNA transcription or processing.

Abelson murine leukemia virus↗
PubMed1984

Expression of transferrin receptor on murine hematopoietic progenitors.

We have used a monoclonal antibody against the murine transferrin receptor to study the expression of the transferrin receptor on the hematopoietic progenitor cells (BFU-E, CFU-E, and CFU-C) present in mouse bone marrow. Elutriation and cell-sorting data are consistent with the hypothesis that most CFU-E are transferrin receptor positive while most BFU-E express much less transferrin receptor. CFU-C comprise both transferrin-receptor-positive and -negative cells.

Animals↗