A dinucleotide repeat polymorphism at the D9S127 locus.
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Biomedical subjects
Publications and source records attributed to M A Yuille.
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Natural killer (NK) activity in peripheral blood mononuclear cells is augmented by products released by two different strains of streptococci. This property is due at least in part to an erythrogenic toxin (ET). A preparation of physiologically active ET from strain NY5 group A beta-hemolytic streptococci and streptococcal products (SP) derived from the culture supernatants of ATCC strain 19165 group A streptococci were both potent inducers of NK activity. An anti-serum to ET reacted with two polypeptides in SP, one of which comigrated with ET when analyzed by SDS-PAGE. Using an affinity column with an antiserum to ET known to neutralize its mitogenic properties, the NK-enhancing activity of ET and SP was partly absorbed and was recovered upon elution. These findings suggest that immunologically related ETs in different streptococcal strains play a role in the activation of NK cells. This novel property of streptococci may feature in the pathogenesis of streptococcal infections and their protean manifestations.
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We studied the prevalence of four serum factors in individuals at different stages of human immunodeficiency virus-1 (HIV-1) infection. Soluble interleukin-2 receptors (sIL-2R) were elevated in all antibody-positive groups compared with high-risk, antibody-negative controls. Paraproteins, usually of the IgG-kappa isotype, were found in the sera of a significant number of HIV-1-infected individuals as were antibodies to lymphocytes (ALAs). Serum factors that inhibit proliferation of peripheral blood mononuclear cells from healthy donors appear late in the course of infection and were associated with increasing clinical severity. Measurement of these factors may prove to be useful in defining the stages of infection and in predicting the appearance or exacerbation of symptoms. They may also play a role in the development of the HIV-1-induced immune defects that lead to the expression of clinical acquired immunodeficiency syndrome.
Terminal deoxynucleotidyl transferase (TdT) is a template-independent DNA polymerase that is transiently expressed during the normal development of T and B lymphocytes. Phorbol 12-myristate 13-acetate (PMA) has been reported to induce maturation-like changes, including the loss of TdT, in many leukemic cell lines. We investigated the mechanism of TdT repression by PMA in an early thymocyte-like cell line, RPMI 8402. At a concentration of 8 nM, PMA caused both repression of TdT synthesis and arrest of proliferation. At greater concentrations of PMA, these same changes initially occurred, but then cell proliferation resumed, and TdT was reexpressed. At both 8 and 160 nM PMA, TdT biosynthesis and TdT mRNA became undetectable within 8 hours, while cell proliferation and DNA synthesis were not significantly reduced until 16 hours. Growth arrest induced by serum starvation did not result in a similar reduction of TdT RNA even after 48 hours. With 160 nM PMA, TdT mRNA could be detected again by 24 hours, and proliferation resumed. Transcription run-off assays indicated that TdT RNA synthesis ceased within 1 hour after exposure to both 8 and 160 nM PMA. T cell receptor alpha (TcR alpha) RNA was induced when TdT RNA was repressed. TcR beta RNA levels were unchanged, and TcR gamma RNA was up-regulated. TdT gene repression and modulation of cell proliferation as well as induction of TcR gene expression are normal events during intrathymic T cell maturation. This cell model provides a system for analyzing the molecular regulation of these significant developmental events.
In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane expression of CD4, we have measured several parameters of CD4 expression in the human tumor T-cell lines CEM and MOLT-4 at different times after infection. Three independent HIV-1 isolates were used including one that encodes a truncated nef protein and another that appeared to be noncytolytic against CEM. The level of CD4 mRNA, the rate of biosynthesis of CD4 protein, and the percentage of CD4-positive cells were measured. With each viral isolate it was found that infection led to a specific and almost complete inhibition of CD4 protein biosynthesis. This substantially exceeded, at every time point after infection, a concomitant reduction in CD4 mRNA. Hence an inhibition of translation probably accounts for much of the decline in the rate of CD4 biosynthesis. This implicates a novel selective translational inhibition of host gene expression by HIV-1 as a factor in the disappearance of surface membrane CD4 from infected cultures.
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