Biomedical subjects
S J Geyer
Publications and source records attributed to S J Geyer.
Kinetics of early HIV-1 gene expression in infected H9 cells assessed by PCR.
The time course of viral gene expression in H9 cells acutely infected with HIV-1 was analysed by the polymerase chain reaction (PCR). Virus-specific sequences were first detected in genomic DNA of H9 cells 1-2 h after infection. RNA for the regulatory genes such as the tat and nef appeared 2-3 h post-infection and RNA for the gag and env at 3 h. The results demonstrate that viral DNA synthesis occurs rapidly after infection of target cells followed by synthesis of viral RNA. Cell-associated reverse transcriptase activity increased after 24 h, while culture supernatant enzyme activity increased later, between 1-5 days. The delay in virus release after rapid integration and transcriptional activity suggests the involvement of additional factors, perhaps both cellular and viral, that control the formation and budding of mature virions.
Chemically induced CD4 mutants of a human T cell line. Evidence for dissociation between binding of HIV I envelope and susceptibility to HIV I infection and syncytia formation.
This study describes the derivation of a series of mutants from the human leukemic cell line CEM using the frame shift mutagen Ethyl-methanesulfonate followed by negative selection with multiple treatments of OKT4A + C, and sorting into CD4-, CD4-dull, and CD4-intermediate mutants. These mutants express reduced CD4 levels ranging from 0 to 60% of the parental line. The mutants were analyzed by staining with a battery of CD4-specific mAb, by assessing their ability to bind soluble gp120, and by their ability to form syncytia after infection with cell-free HIV I virus and a gp160-vaccinia vector. Two groups of particularly interesting mutants were identified: (1) CD4-dull mutants expressing only 5 to 10% of the wild type surface CD4 density, which nevertheless were infectable by HIV I and produced as many syncytia and reverse transcriptase activity as the parental line after infection with gp160-vaccinia or cell free HIV I. (2) CD4-intermediate mutants (30 to 60% of parental CD4 level), which express CD4-epitopes required for interaction with the HIV I envelope protein, yet are markedly deficient in their ability to form syncytia after gp160-vaccinia or HIV I infection. Two of these mutants did form syncytia after transient reconstitution with a wild type CD4 containing vaccinia vector. Inasmuch as they were found to bind soluble gp120 with the same avidity as other, functionally normal, CD4-intermediate mutants, these human T cell mutants may have a reduced susceptibility to HIV I infection due to the absence of a "fusogenic component" or to a structural alteration in a region of the CD4 molecule not required for binding of the HIV I envelope, but for the subsequent fusion and entry process.
The normal parathyroid gland at autopsy: the significance of stromal fat in adult patients.
Traditionally half of the cell population of the adult parathyroid gland is considered to be stromal fat. A marked decrease of stromal fat has been observed at autopsy of adult patients, the functional significance of which is unknown. In order to investigate this phenomenon, the stromal and parenchymal fat of the parathyroid glands of 33 adult patients who died with no known hormonal abnormalities were evaluated. Stromal fat was much less than 50 per cent, i.e., less than 10 per cent., in the majority of cases, while parenchymal fat was ample in all cases. This finding, especially if compared to cases with hyperparathyroidism, indicates the lack of functional specificity of change in stromal fat, whereas, alteration in parenchymal fat appears to be a better anatomical register of normal or abnormal parathyroid function.
Myxomatous degeneration of the mitral valve complicated by nonbacterial thrombotic endocarditis with systemic embolization.
Myxomatous degeneration of the mitral valve is a disease of unknown etiology that is associated with many ominous complications. A case in which non-bacterial thrombotic endocarditis, superimposed on a myxomatous mitral valve, resulted in systemic embolization to the brain, heart, and kidney is presented. The purpose of this report is to describe a serious and previously unreported complication of myxomatous degeneration of the mitral valve.
Immunogenetic aspects of intracerebral skin transplantation in inbred rats.
This study was undertaken to evaluate the ability of intracerebral skin grafts transplanted across different genetic disparities in the major histocompatibility complex (RT1) to elicit an immune response in inbred rats, as determined by histologic examination and by the ability of the grafts to sensitize the recipients to subsequent orthotopic skin grafts. The ability of intracerebral skin allografts to sensitize rats to transplantation antigens is related to the specific genetic disparity between the graft and the host: sensitization appears to occur more consistently across an A region barrier than across a B region barrier. Histologic changes of intracerebral graft rejection are more severe in rats with two intracerebral grafts than in those with one. The degree of histologic change attributable to intracerebral allograft rejection correlates with the ability of these grafts to sensitize the recipient. In certain strains intracerebral sensitization is accomplished with two grafts but not with one, indicating an antigenic dose requirement for intracerebral sensitization.
Immunogenetic control of brain tumor growth in rats.
The susceptibility to intracerebral and s.c. growth of a transplantable gliosarcoma in genetically inbred rats correlated with histocompatibility type. The genetic control of tumor growth was tested in a cross between a tumor-susceptible strain (F344, Ag-B1) and a tumor-resistant strain (YO, Ag-B2). Susceptibility was transmitted as a dominant trait, and at least two genes or gene complexes were involved: one was linked to the major histocompatibility complex and one segregated independently of it. The genetic mechanisms did not appear to be affected significantly by the site (environment) in which the tumor grew. Antibodies to Ag-B1 histocompatibility antigens, which were those of the strain in which the tumor originated (F344), and to tumor-associated antigens were generally present in animals in which the tumor had regressed. Only tumor-specific antibodies appeared in the sera of Ag-B1 animals that had the tumor. A cytotoxic lymphokine was present in the sera of tumor-bearing animals, but its level did not correlate with tumor growth or regression.