SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones

The HLA-D region of the human major histocompatibility complex (MHC) has been shown to be homologous to the murine I region in terms of both structure and function. Both regions encode class II MHC molecules which restrict T-lymphocyte interactions with antigen-presenting cells. We have recently described the MHC restriction and antigen specificities of human T-lymphocyte clones directed at strain A influenza virus. The majority of T-lymphocyte clones recognized antigen in the context of cell surface interaction products encoded by HLA-D/DR genes. However, a few clones recognized antigen presented by cells histoincompatible for D/DR antigens. We report here that some of these clones recognized viral antigens in association with antigens encoded by genes identical with or closely linked to the recently described secondary B-cell (SB) locus of the MHC. This is the first report that SB-restricted antigen recognition may form an integral part of normal, human immune responses.     

Steady-state kinetic studies with the polysulfonate U-9843, an HIV reverse transcriptase inhibitor

The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT^* and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed RNA-directed DNA polymerase activity were carried out in order to determine if the inhibitor interacts with the template: primer or the deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics, which are based on the establishment of a rapid equilibrium between the enzyme and its substrates, proved inadequate for the analysis of the experimental data. The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming that the template:primer binds to the enzyme first, followed by the binding of the dNTP and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived which allows the calculation of all the specific forward and backward rate constants for the reactions occurring between the enzyme, its substrates and the inhibitor. The calculated rate constants are in agreement with this model and the results indicated that U-9843 acts as a noncompetitive inhibitor with respect to both the template:primer and dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase by interacting with a site distinct from the substrate binding sites. Thus, U-9843 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either an event leading up to the formation of the phosphoester bond, the formation of the ester bond itself or translocation of the enzyme relative to its template:primer following the formation of the ester bond.     

Age-related lipid peroxidation in the digestive gland of mussels: The role of the antioxidant defence systems

Summary The main cellular defence systems against free radical-mediated oxidative stress are significantly reduced in the dige⁺ive gland of aged (>10 years old) compared to younger (2–4 years old) mussels (Mytilus edulis L.). Moreover, the concentration of lipid peroxidation products (malondialdehyde) is increased in the same age group with respect to younger animals. The obtained data indicate that an impairment of the antioxidant defence systems would render the older animals more susceptible to peroxidative stress, thus supporting the general significance of the free radical theory of aging.     

The effect of cycloheximide on nuclear uH2A content

Summary The effect of intraperitonal cycloheximide administration on acid-soluble rat liver chromatin proteins has been investigated by electrophoresis in acetic acid-urea polyacrylamide gels. A nonhistone protein, which migrates between oxidized histone H3 and histone H1 has been found tobe increased in amount following cycloheximide treatment. This protein seems to be identical with semihistone protein H24 (uH2A). A possible relationship of uH2A to the inhibition of rRNA synthesis is discussed.This work was supported by the Turkish Scientific and Technical Research Council (TUBITAK) Project No. TAG 339     

(3H) spiroperidol binding decreases in brains of rats infected with Venezuelan equine encephalomyelitis virus1

Summary After i.p. inoculation with the Guajira strain of Venezuelan equine encephalomyelitis virus a significant decrease in the density of (³H) spiroperidol binding sites in the striatum, midbrain and frontal cortex was observed. No changes in the affinity of the receptors could be demonstrated. This finding is compatible with neuronal degeneration caused by the viral infection.Acknowledgments. This work was partially supported by Condes-Luz and Fundacite-Zulia. Butaclamol isomers were a gift of Ayerst Laboratories, Montreal, Canada.     

Comparative distribution of vasoactive intestinal polypeptide (VIP), substance P and PHI in the enteric sphincters of the cat

In the feline gastrointestinal tract, the neuropeptides, substance P, VIP and PHI were investigated by specific radioimmunoassays and immunocytochemistry. The concentrations of all 3 peptides and the level of peptidergic innervation were significantly less in the anal sphincter than elsewhere, whereas no significant differences were seen between other sphincter and non-sphincter regions.