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Biomedical subjects

V Rossi

Publications and source records attributed to V Rossi.

At least 127 records · Page 7Linked to original sources

Ia antigen expression and IL-1 activity in murine tumour-associated macrophages.

Tumour-associated macrophages (TAM) isolated from five murine sarcomas had a relatively high frequency of I-A+ cells, with mean values of 27% (mFS6), 52% (MN/MCA1), 68% (N3), 62% (N4) and 98% (J3) for TAM compared to 12% for resident peritoneal macrophages. Expression of I-E in TAM was also high (29%) in the only sarcoma (N4) examined in this respect. Expression of I-A by TAM declined in culture but exposure to lymphokine supernatants maintained and increased the frequency of I-A+ cells in TAM. Transplantation of tumours into nude mice caused a marked decrease in the percentage of I-A+ TAM in the case of the N4 sarcoma (8% compared to 48%), whereas for the MN/MCA1 sarcoma the diminution was only marginal (from 53 to 41%), TAM from murine sarcomas did not constitutively release appreciable levels of interleukin-1 (IL-1) activity. Upon stimulation with bacterial lipopolysaccharides or silica, TAM showed a limited capacity to produce and release IL-1 activity compared to peritoneal macrophages. Thus the expression of I-A antigens and the IL-1-producing capacity are uncoupled in TAM from murine sarcomas. These properties of TAM could play an important role in the generation of anti-tumour immunity and/or of suppressive T-cell circuits.

Animals↗

Prostacyclin synthesis induced in vascular cells by interleukin-1.

Supernatants from cultures of human monocytes that had been stimulated with endotoxin or silica induced the synthesis of prostacyclin in endothelial and smooth muscle cells. The lymphokine mediating these effects on the cells of the blood vessel wall was identified as interleukin-1; interferons and interleukin-2 were inactive. Interleukin-1-induced prostacyclin synthesis represents a new aspect of the interaction between the immune system (as well as other tissues) and the vessel wall and may serve as a basis for the development of new strategies in antithrombotic therapy.

Blood Vessels↗

Production of interleukin 1 but not of procoagulant activity by large granular lymphocytes.

Large granular lymphocytes (LGL) share phenotypic and functional properties with monocytes. We have investigated the production of procoagulant activity (PCA), so far attributed to cells of the monocyte-macrophage lineage, by LGL. Endotoxin triggered interleukin (IL-1) release and PCA activity by highly purified monocyte preparations. In contrast, LGL exposed to endotoxin produced IL-1 but had no PCA activity. Similarly ineffective in inducing PCA in LGL were other stimuli that either triggered monocyte PCA or stimulated the natural killer cytotoxicity of LGL. Thus, although LGL share properties with monocytes such as the capacity to produce IL-1, PCA is confined, among circulating leukocytes, to cells of the monocyte lineage.

Antibodies, Monoclonal↗

Monocyte function in intravenous drug abusers with lymphadenopathy syndrome and in patients with acquired immunodeficiency syndrome: selective impairment of chemotaxis.

We have investigated monocyte function in 17 intravenous drug abusers with the clinical and laboratory features of lymphadenopathy syndrome (LAS). LAS patients had normal numbers of circulating monocytes. Monocytes from LAS patients were comparable to cells from normal donors in terms of phagocytosis of latex beads, interleukin-1 secretion, O2- release and killing of antibody-sensitized lymphoma cells or actinomycin D pretreated WEHI 164 cells. In contrast 13 out of 17 LAS subjects tested in this respect as well as six out of nine AIDS patients showed a marked defect of monocyte chemotaxis. Thus monocytes from patients with LAS or AIDS have a selective defect of monocyte chemotaxis.

Acquired Immunodeficiency Syndrome↗

A comparative study of acute toxicity of drugs used during anticancer therapy in healthy and tumor-bearing mice.

A comparative study was performed, in healthy and Ehrlich ascites bearing mice, to ascertain if the acute toxicity of drugs can change in disease conditions. Adriamycin, cis-platinum, cyclophosphamide, 5-fluorouracil, vinblastine, morphine and cefoxitin were administered intravenously; prochlorperazine and acetylsalicylic acid were given orally, and dexamethasone and lonidamine were given by both routes. With the exception of morphine, the LD50's significantly decreased in tumor bearing animals. The highest potency ratios (about 4-6) were observed with prochlorperazine and cyclophosphamide and the lowest (1.3-1.4) with lonidamine given intravenously, adriamycin and acetylsalicylic acid. These results confirm that the toxic response may be strongly influenced by pathological states.

Animals↗

Monoclonal antibody-defined surface markers of effector cells involved in human monocyte cytotoxicity.

Human adherent peripheral blood mononuclear cells were cytotoxic in vitro against the murine TU5 line in a 48-hr [3H]thymidine-release assay. Monocyte-enriched adherent cell preparations contain a small and variable (usually less than 5%) contamination with large granular lymphocytes as assessed by morphology and staining with monoclonal antibody markers B73.1 and HNK1. To assess whether killing was in fact mediated by monocytes, mononuclear cells or monocyte-enriched preparations were separated using monoclonal antibodies directed against mononuclear phagocytes (Mo2, UCHM1, B44.1) or natural killer (NK) cells (B73.1 and HNK1), and a fluorescence-activated cell sorter. Cells positive for monocyte markers were highly cytotoxic against TU5, whereas negative cells were not. B73.1+ or HNK1+ cells had little or no activity. Cytotoxicity of cells positive for monocyte markers (Mo2, UCHM1, B44.1) was augmented by in vitro exposure to lymphokines or less frequently to interferon (IFN). However, cells negative for these monocytes markers were also stimulated to kill TU5 by lymphokine or IFN to an extent similar or greater than that of positive ones. IFN or lymphokines induced killing of TU5 by monocyte-depleted, B73.1-positive, lymphoid cells. These observations demonstrate that human monocytes do kill tumor cells, either in the absence of deliberate stimulation or after exposure to agents such as lymphokines. However, the possible contribution to "monocyte" cytotoxicity of minor NK cell contaminants must be taken into account particularly when agents such as IFN and lymphokines are applied, even when a relatively NK-cell-resistant target such as TU5 is used.

Antibodies, Monoclonal↗

Stimulation of prostacyclin synthesis in vascular cells by mononuclear cell products.

Supernatants were obtained from human peripheral blood mononuclear cells stimulated with phytohemagglutinin or in a mixed lymphocyte reaction. The effect of mononuclear cell products on vascular prostacyclin (PGI2) production was measured using cultured rat aortic smooth muscle cells (SMC) or aortic rings. PGI2 was measured by radioimmunoassay of its metabolite, 6-keto-PGF1 alpha. Supernatants containing mononuclear cell products induced PGI2 production in vascular tissue. Supernatant-induced PGI2 production of SMC was relatively slow, requiring more than six hours of incubation with supernatants, and was completely prevented by aspirin, a cyclooxygenase inhibitor. The regulation of arachidonic acid metabolism by products of stimulated mononuclear cells, which is critical to the physiology and pathology of blood vessels, may be an important aspect of the interaction between immunocompetent cells and vascular tissue.

6-Ketoprostaglandin F1 alpha↗

Pharmacological investigations on lonidamine.

The results of a broad pharmacological screening on 1-[(2,4-dichlorophenyl)-methyl] -1H-indazole-3-carboxylic acid ( lonidamine ) a new antitumour agent which also possesses antispermatogenic and embryotoxic effects, are reported. Lonidamine does not affect general behaviour and autonomic functions and is devoid of anticonvulsant, anti-reserpine, anti-apomorphine, anti-amphetamine, antitremor , antipyretic, antiinflammatory and analgesic effects. It also lacks those side effects which are considered characteristic of different antitumour agents, such as thymus and spleen atrophy, delay in skin wound healing and damage to the gastrointestinal mucosa. At doses 40 times higher than that of hydrochlorothiazide, lonidamine produces diuretic effects. The practical importance of these findings in the current therapeutic use of lonidamine appears to be limited. The most typical signs of acute intoxication produced by high doses of lonidamine are salivation, lacrimation, diarrhea, ataxia, muscle rigidity and prostration with superimposed convulsions.

Animals↗

Spectroscopic study on the structure and stability of beef liver arginase.

The secondary and tertiary structure of the oligomeric arginase (EC 3.5.3.1) from beef liver was investigated by circular dichroism (CD) and fluorescence measurements. The far-ultraviolet CD spectrum of the enzyme at neutral pH is indicative of high helical content. The intrinsic fluorescence emission of the protein is due to tryptophan, the contribution of tyrosine being small. Upon excitation at 295 nm, the maximum of emission occurs at 330 nm, implying that the tryptophan residues are rather buried in a hydrophobic interior of the protein. Ethylenediaminetetraacetic acid (EDTA), which inactivates the enzyme by removing the functional Mn2+-ion from the enzyme, does not dissociate the enzyme into subunits, nor affect noticeably its secondary and tertiary structure. Inactivation occurs in the acid pH range, being complete at pH below 4. However, acidification up to pH 1.5 produced only limited changes in the far-ultra-violet CD spectrum and intrinsic fluorescence emission properties. The enzyme shows noteworthy thermal stability, as shown by measuring the residual activity after heating and by evaluating the temperature dependence of the CD signal at 220 nm and the intensity of emission fluorescence. A temperature of half inactivation (Tm) of 77 degrees was determined upon heating the enzyme at pH 7.5 in the presence of Mn2+-ions for 10 min; in the presence of EDTA, Tm is shifted to 55 degrees. Taken together, these observations indicate that the structural stability of beef liver arginase arises from a clustering of hydrophobic amino acids and from Mn2+-ion binding.

Animals↗

Hollow fiber immobilized L-asparaginase: in vivo and in vitro immunological studies.

The enzyme L-asparaginase was covalently immobilized on the inner surface of the hollow fibers utilized in a commercially available dialyzer by the periodate method. After sterilization with gamma radiation the bioreactor was able to metabolize in vivo, 90 per cent of circulating asparagine in two hours. The absence in blood of asparaginase-related protein fragments, released from the hollow fiber immobilized enzyme, was monitored using a specific enzyme-linked immunosorbent assay (ELISA).

Antibodies↗

Immobilization of arginase on hollow fiber hemodialyzer.

The enzyme arginase, purified from bovine liver, was covalently immobilized by the glutaraldehyde method to the inner surface of Cuprophan hollow fibers of a conventional hemodialyzer with a surface 1.3 m3. The yield of the process was 0.3 microgram/cm2 of active enzyme at physiological pH. The immobilization method did not adversely affect the physical and mechanical properties of hollow fibers neither their hemocompatibility. After sterilization with ethylene oxide, the bioreactor was able to metabolize five liters of 50 microM arginine solution at pH 7.4, in six hours.

Arginase↗