Human T-cell leukemia/lymphoma virus (HTLV I) DNA: detection in Italy in a lymphoma and in a Kaposi sarcoma patient.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to L Frati.
Explore the source record for details and available documents.
The in vitro influence of cytosine-arabinoside (Ara-C) on mouse NK activity was studied treating effector cells, target cells or effector and target mixture with graded concentrations of the drug. Ara-C increased the NK efficiency of mouse splenocytes without enhancing the susceptibility of target cells or the cytolytic events when added to effector-target mixture. This phenomenon was confirmed with splenocytes collected from congenitally athymic (nude) or conventional donors of different ages, untreated or depressed or boosted for NK activity by various agents. In addition Ara-C increased the NK activity of spleen cells of nude mice deprived of nylon-adherent cells, and did not affect suppressor cells capable of inhibiting the lytic phase of NK process. The drug was able to significantly augment the binding ability of spleen cells to the NK-sensitive YAC-1 target. It was concluded that Ara-C would increase the efficiency of natural cytotoxicity presumably through a direct influence on effector lymphocytes.
We analysed the phenotypic characteristics of mouse NK cells susceptible to boosting activity by T-cell-growth-factor (TCGF) and the characteristics of NK-cell progenitors able to grow in vitro in the presence of TCGF. Our data show that while both the above-mentioned cell populations are Asialo GM-1+, they differ in the expression of Thy 1 alloantigen. In addition, we also analysed the possible regulatory mechanisms capable of influencing the growth of TCGF-sensitive NK-cell progenitors. The data here reported suggest that the growth capability of NK cell progenitors is under the control of the thymus.
Mouse YAC-1 and human K562 leukemic cells were treated in vitro with fibroblast interferon (IF) and tested for their susceptibility to NK effector lymphocytes. In both cases a decrease in target susceptibility was induced by the IF treatment. "Cold" competition experiments confirmed that loss or masking of NK target structures occurred in IF-pretreated cells. In fact, when radio-labeled untreated cells were used as targets, IF-pretreated leukemias produced inhibitory effects lower than those mediated by intact cells. However when IF-pretreated targets were used, cold cells either intact or preincubated with IF gave similar competitive effects. These data suggest that IF modulates differentially distinct subsets of NK target structures.
We analyzed the effects of a polycythemic substrain of Friend leukemia virus, i.e. the FLV-P virus, on splenic NK activity of DBA/2 susceptible mice. One day after virus injection a significant increase of NK activity was found, which persisted until day 10. On the other hand, 14-21 days after virus injection a marked and significant depression of activity was measured. This depression was associated with the appearance of suppressor cells able to inhibit the lytic activity of untreated splenocytes when mixed in vitro in the 4 h 51Cr-release assay. The suppressor cell population was insensitive to treatment with anti-Thy 1.2 plus complement, was adherent to Sephadex G-10 and nylon, but did not adhere to plastic, suggesting it is neither a T-cell nor a typical macrophage. The possible relevance of NK activity modulation in relation to the induction of leukemia is discussed.
Explore the source record for details and available documents.
1. The behaviour of ATPase activity during embryonic development of chick embryo epidermis has been studied in the absence or presence of a single inoculation of EGF at the fifth day from fertilization (0-day). 2. EGF strongly decreases ATPase activity by affecting Na+/K+ ATPase. This effect occurs only if begun at 0-day. 3. This effect is due to the EGF induced decrease of -SH groups that are active part of Na+/K+ ATPase.
1. The behaviour of Na+/K+ ATPase during the growth of ectodermal tumoral cells (HeLa) has been investigated. 2. Besides spontaneously growing cells, also samples stimulated with EGF have been tested. 3. The content of--SH groups in the homogenates of both the untreated and the EGF stimulated samples has been tested. 4. Results show a decrease of enzymatic activity during the culture of neoplastic cells and an enhancement of this behaviour in the EGF stimulated cells due to the action of the hormone on--SH groups.
The combined effects of nonspecific immunostimulation with Candida albicans (CA) and chemotherapy were studied in (BALB/cCr X DBA/2Cr)F1 and (C57BL/6Cr X DBA/2Cr)F1 mice bearing virus-induced LSTRA lymphomas. Paradoxically, animals treated with a relatively high number of tumor cells responded better to therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) than those challenged with a low number of tumor cells. However, the majority of mice subjected to low initial tumor load were cured when they were treated with chemotherapy or chemotherapy plus booster injection of CA at a relatively "late" stage of the disease, i.e., when high tumor load was present in tumor-bearing hosts. It has been shown that this phenomenon, provisionally called high tumor load protection, occurs when the animals are challenged ip but not when they are challenged iv with the tumor and is abolished by total-body gamma-irradiation. Moreover, marked host protection can be attained when immunostimulated mice, inoculated iv with lymphoma cells, are subjected to simultaneous challenge with high inocula of the same tumor ip, followed by BCNU administration. These data stress the importance of the peritoneal cavity for successful CA plus drug treatment and suggest that optimal tumor "antigen load" should be present at the time of CA and/or BCNU administration.
The influence of the route of administration and treatment schedule of a yeast immunoadjuvant, Candida albicans (CA) on the degree of success achieved with an immunochemotherapy regimen in a virus-induced murine lymphoma has been evaluated. To this end, histocompatible CD2F1 mice received IP or IV inoculations of LSTRA lymphoma cells and were subjected to various treatments with inactivated CA and bis,1,chloroethyl nitrosourea (BCNU). The results showed that CA may significantly increase the antitumor efficiency of BCNU when (a) the tumor is inoculated IP and not IV; (b) CA is administered before (on day -14) and after (on days +1 and/or day +8) LSTRA challenge; (c) CA is given IP as a post-tumor treatment. To ascertain whether the immunoadjuvant effect was anatomically restricted to the peritoneal cavity (PC), spreading of IP injected lymphoma was studied by means of LSTRA cells labeled with 3-5'iodo-deoxyuridine 125I (125IUdR) and tumor bioassay in spleen, lung, kidney, liver, and PC of recipient mice. The results showed that IP tumor challenge led to early (1 h) generalized neoplasia in both untreated and CA-pretreated hosts. Therefore, the combined antitumor effects of chemotherapy and CA are not restricted to the PC but rather the result of systemic immunity. In conclusion, in our system the PC seems to be a preferential site for eliciting generalized antilymphoma host responses markedly amplified by selected schedules of immunoadjuvant administration.
Studies were carried out to assess the ability of thymosin alpha 1 to prolong the survival of mice challenged with Candida albicans. Two- to four-month-old mice were treated with graded doses of thymosin alpha 1 before, after, or before and after intravenous challenge with C. albicans. Significant resistance ot lethal infection was afforded by 100 micrograms of thymosin alpha 1 per kg given before or before and after challenge, whereas no protection was found in mice treated with thymosin alpha 1 administered at any dose level after inoculation. Pretreatment with thymosin alpha 1 also prevented the increased susceptibility to C. albicans infection of mice pretreated with cyclophosphamide on day -6. The results showed that thymosin alpha 1 was capable of protecting untreated or cyclophosphamide-pretreated mice from C. albicans infection at an optimal dose and schedule of administration.
The behaviour of Na+/K+ ATPase during cell growth has been studied. Enzymatic activity, which is slightly affected during normal growth, is strongly reduced if the cells are incubated with epidermal growth factor (EGF). Evidence indicates that there is a double mechanism of action of the hormone.
The possible influence of Vincristine (VCR) on NK-mediated cytolysis has been studied pretreating effector (E) or target (T) cells with the drug or adding the agent to E + T mixture during the 18-hour assay. Substantial increase of cytotoxicity was found when VCR was added to E + T cells, but not when effector or target cells were pretreated with the drug. This phenomenon was confirmed with effector splenocytes of various strains of mice, including athymic nude donors deprived of plastic-adherent or nylon-wool adherent accessory cells. Moreover, the agent did not produce irreversible inactivation of the suppression activity of splenocytes collected from DBA/2 donors infected with Friend leukaemia virus.
Mouse T-lymphocytes carrying the H-2d haplotype were sensitized in vitro against allogeneic spleen cells homozygous for the H-2b haplotype. Cytolytic T-lymphocytes (CTL) were tested in a 4 hr cytotoxicity assay against 51Cr-labeled H-2b RBL-5 lymphoma cells. The cytotoxic activity of CTL was markedly increased by preincubation with Ara-C (1 through 1000 micrograms/ml, 1 hr at 37 degrees C). Limited but significant increase of cytotoxicity occurred when the drug was added to the effector-target mixture, or when target cells were preincubated with Ara-C using the same conditions adopted for the in vitro treatment of CTL. It is suggested that the present findings would contribute to elucidate the mechanism underlying antitumor synergistic effects between host's responses and treatment with antineoplastic agents.
Epidermal growth factor (EGF) is a polypeptide hormone present in mammalian organs. In vivo, it shortens the time course of the corneal reepithelialization by stimulating a marked cell proliferation of the corneal epithelium. A further direct effect in vivo has been confirmed on human corneal epithelium and epidermis in culture. Tests in several nondystrophic diseases of the corneal epithelium confirmed the observations previously made in the rabbit that EGF accelerates the process of epithelial healing. The integrity of the corneal stroma is prejudicial for the maximum effect of the EGF, in the sense that the deeper the stroma is damaged, the less EGF acts. In herpetic lesions EGF is effective within 48 h only when the virus-affected area of the corneal epithelium has been scraped off. EGF is proposed as a new and efficacious agent for increasing the restorative process of the corneal epithelium in many nondystrophic diseases.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
[125I]5-iodo-2'-deoxyuridine ([125I]UdR) was compared with [6-3H]thymidine ([3H]TdR) in a semi-micromethod used to evaluate the response of human lymphocytes to phytohemagglutinin (PHA) in vitro. 5-Fluoro-2'-dexoyuridine (FUdR) was added to [125I]UdR in order to increase its incorporation, by preventing endogenous thymidine synthesis. The relationship between PHA concentration and the isotope uptake by lymphocytes was studied. Similar dose-response curves were found for the two precursors, with a peak at 15 microgram/ml of PHA. Nevertheless the recovery of the labeled compounds was higher when [125I]UdR together with FUdR was used.