Varicella-zoster virus infection of human mononuclear cells.

Varicella-zoster virus (VZV) DNA was detected in mononuclear cells (MNC) of 7 humans with acute zoster 1-23 days after the onset of skin lesions. To further study the interaction of VZV with human MNC, cells obtained from seropositive normal donors were infected with VZV and analyzed for the presence of viral DNA and proteins. VZV-DNA was detected in T, B, and OKM 1 (monocyte-macrophage) positive cells, and virus-specific proteins were demonstrated by indirect immunofluorescence and immunoprecipitation. Hybridization studies revealed that VZV-DNA did not replicate in human MNC.

Synergistic interaction in Jensen tumor cells of two modes of exposure to inosine that potentiate the cytotoxicity of 5-fluorouracil.

The cytotoxicity resulting from a 1-h exposure of Jensen tumor (JT) cells to 5-fluorouracil (FUra), quantified in terms of growth delay, was potentiated 4.1-fold if inosine was included in the culture medium for 30 min prior to and for 1 h concurrently with drug uptake. In contrast, as reported previously, protection from FUra toxicity is induced if the cells are exposed successively to inosine for 1.5 h and to FUra for 1 h. Anabolic conversion of radiolabeled FUra to free and polymeric nucleotides was stimulated by the cytotoxicity-enhancing mode of inosine exposure but inhibited by the inosine exposure that protects against FUra. Continuous exposure of JT cells to inosine after a 1-h uptake of FUra was reported earlier to potentiate drug efficacy 5-fold. Treatment of cultures by both modes of inosine exposure that enhance FUra cytotoxicity resulted in a 15.8-fold potentiation of the latter.

Thrombin activity induced by balloon angioplasty of the coronary artery in Macaca fascicularis (cynomolgus monkey).

In this paper we address the question of whether balloon angioplasty induces thrombin action. In the studies reported here we measured fibrinopeptide A levels in a group of atherosclerotic monkeys undergoing coronary angioplasty. A blood collection catheter was introduced into the inferior vena cava through a femoral vein, and the angioplasty catheter introduced via the femoral artery. Heparin was administered immediately after insertion of the arterial catheter. Serial blood samples were collected for 20 min before angioplasty and for 10 min after angioplasty. Baseline levels of FpA were high, presumably in response to the trauma of introducing the catheters. After heparin administration the FpA concentration declined with a half-time of 1.1 min. In response to balloon inflation there was a clear increase in the concentration of FpA, despite the presence of a therapeutic concentration of heparin. The magnitude of the FpA rise was markedly different between animals, but was evident in the aggregate data after subtraction of background levels of FpA. By integration of the plasma FpA concentration curve, the amount of fibrinogen converted to fibrin in response to angioplasty was calculated to be approximately 0.4 mg/animal. We conclude that angioplasty induces significant activation of the coagulation system.

Inhibition of herpes simplex virus type 1 replication in fibroblast cultures by human blood mononuclear cells.

An assay was developed to test the effect of human blood mononuclear cells (MNCs) on herpes simplex virus (HSV) replication. In this assay, human fibroblast monolayers were inoculated with HSV and then cultured with or without blood MNCs. Fewer HSV-infected cells were recovered from human fibroblasts cultured in the presence than in the absence of blood MNCs. This inhibition of viral replication by MNCs was independent of HLA matching between the MNCs and fibroblasts and persisted even when T cells were depleted by antibody and complement. However, depletion of Leu11+ MNCs either by panning or with antibody and complement reduced the ability of the cells to suppress HSV infection, whereas enrichment of Leu11+ cells by fluorescence-activated cell sorting increased the viral suppression. Depletion of OKM1+ MNCs also reduced the viral suppression. After coculturing of MNCs and HSV-infected fibroblasts for 3 days, alpha interferon (IFN) and gamma IFN were detected in the supernatants. Predepletion of Leu11+ MNCs reduced the amount of gamma IFN produced in these cultures. Incubation of the MNCs and HSV-infected fibroblasts with antibody specific for either alpha or gamma IFN resulted in reduced viral suppression. Preincubation of MNCs for 18 h with either interleukin 2 or alpha IFN or for 7 days with antigen increased the suppression of HSV infection. These results suggest that natural killer cells with the Leu11+ phenotype participate in the recognition of HSV-infected cells at a point sufficiently early to interfere with the spread of infection in vitro and may inhibit viral replication by natural killer cell cytotoxicity, by generation of interferon, and by lymphokine-activated killing.

Impaired neonatal natural killer-cell activity to herpes simplex virus: decreased inhibition of viral replication and altered response to lymphokines.

Human adult natural killer (NK) cells were recently demonstrated to inhibit herpes simplex virus (HSV) replication in vitro. In this study we compared the ability of newborn and adult NK cells to inhibit HSV replication. Cord blood mononuclear cells (MNCs) from healthy, term newborns and MNCs from adults were analyzed for their percentage of Leu-11+ cells and compared in vitro for their NK-cell activity against HSV-infected fibroblasts and the tumor cell line K562. Cord blood MNCs, compared with adult MNCs, had significantly lower percentages of Leu-11+ cells (5 vs 11%; P less than 0.01), less anti-K562 NK activity (6 vs 54 lytic units/10(7) cells; P less than 0.001), and less anti-HSV NK activity (5 vs 52% HSV plaque inhibition; P less than 0.02). Comparing individual neonates and adults with equal percentages of Leu-11+ cells, neonatal MNCs still had less NK activity against either target. When Leu-11+ MNCs were isolated using the fluorescence-activated cell sorter, neonatal Leu-11+ MNCs still inhibited HSV replication less than adult Leu-11+ MNCs (P less than 0.01). MNCs from some neonates had significant anti-K562 NK activity but poor anti-HSV NK activity, suggesting either nonidentical NK-cell subpopulations or specific suppression. Whereas neonatal NK activity against K562 was always augmented by prior exposure to either interferon (IFN) or interleukin-2 (IL-2), the neonatal NK activity against HSV-infected cells was only augmented for half of the neonates tested. Endogenous production of alpha-IFN and gamma-IFN by MNCs exposed to HSV-infected fibroblasts was the same for cells from neonates or from HSV-seronegative adults.(ABSTRACT TRUNCATED AT 250 WORDS)