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Biomedical subjects

A Ferrante

Publications and source records attributed to A Ferrante.

At least 217 records · Page 12Linked to original sources
PubMed1984

Lipopolysaccharide hyperreactivity of animals infected with Trypanosoma lewisi or Trypanosoma musculi.

Rats and mice infected with Trypanosoma lewisi and Trypanosoma musculi, respectively, showed hyperreactivity to lipopolysaccharide (LPS) from gram-negative bacteria. Fatal shock could be precipitated with a dose of LPS 100 to 1,000 times less in infected compared with noninfected animals. In trypanosome-infected rats and mice, extensive liver damage was evident after LPS challenge. These animals showed a pronounced hypoglycemia, marked elevation of blood aspartate transaminase level, and diffuse severe degeneration and total depletion of glycogen in hepatocytes. Only minor changes were observed in noninfected animals given the same dose of LPS. No mononuclear phagocytic cell infiltration was observed in the liver of infected animals. The most striking change was the great increase in size and the probable increase in phagocytic activity and number of sinusoidal Kupffer cells. We suggest that elevated Kupffer cell activity in trypanosome-infected animals may play a role in LPS-induced hepatotoxicity.

Animals↗
PubMed1984

Inhibition of in vitro human lymphocyte response by the pneumococcal toxin pneumolysin.

The effects of pneumolysin, a sulfhydryl-activated cytolytic toxin produced by Streptococcus pneumoniae, on the in vitro human lymphocyte response was examined. The toxin, at concentrations of one to five hemolytic units per ml, caused marked inhibition of the response of lymphocytes to concanavalin A, phytohemagglutinin, pokeweed mitogen, and protein A. The response was assessed by measuring both [3H]thymidine incorporation and the ability of lymphocytes to produce immunoglobulins and lymphokine activity. The effects of pneumolysin were irreversible, could be prevented by pretreatment of the toxin with cholesterol, and were not related to a direct cytotoxic effect on the lymphocytes. Pneumolysin appeared to act at the initiation phase of the immune response and had no effect on lymphocytes committed to DNA synthesis or to the synthesis and secretion of immunoglobulins. Furthermore, pneumolysin-mediated inhibition of the lymphocyte response was not due to the inhibition of binding of mitogens to leukocytes and is likely to be related to effects on membrane-mediated signals essential for lymphocyte triggering. This may be one means by which pneumolysin plays a role in the pathogenesis of pneumococcal infections.

Antibody Formation↗
PubMed1984

Human neutrophils require activation by mononuclear leucocyte conditioned medium to kill the pathogenic free-living amoeba, Naegleria fowleri.

Naegleria fowleri is a free-living amoeba which causes a fulminant and rapidly fatal meningoencephalitis in man. Human neutrophils fail to kill the amoeba in vitro, but can do so if they are exposed to conditioned medium (CM) from PHA stimulated mononuclear leucocytes (MNLs). Specific antibody or complement was required to effect amoeba killing by CM modified neutrophils. Only short time exposure of the leucocytes to CM was required to endow them with amoebicidal properties. The CM was also shown to contain neutrophil migration inhibition activity and an activity(ies) which induced a respiratory burst in neutrophils. The results highlight the importance of MNL products other than specific antibody in neutrophil anti-microbial activity.

Amoeba↗
PubMed1984

Polyamine oxidase-mediated trypanosome killing: the role of hydrogen peroxide and aldehydes.

Trypanosoma lewisi and T. musculi were lysed when incubated with bovine serum in the presence of either spermine or spermidine. Similar results were obtained when a fraction from bovine serum containing polyamine oxidase (PAO) activity or a commercially available purified beef plasma PAO were used in lieu of bovine serum. Trypanosomes treated with cytotoxic concentrations of PAO-spermine failed to establish infection in rats. These results are similar to those from our previous studies with African trypanosomes. We now extend the properties of PAO by showing that human retroplacental serum (RPS) containing PAO activity was also capable of mediating trypanosome killing. This is of significance because the macrophage PAO resembles the human RPS PAO. In addition, our preliminary studies, in which an attempt was made to characterize the factors responsible for cytotoxicity, suggested that a number of products of the PAO-polyamine reaction display trypanocidal properties. These included hydrogen peroxide (H2O2), the aldehyde acrolein, and possibly aminoaldehydes. No evidence was obtained that the oxygen intermediates, superoxide and hydroxyl radicals, play a role in the PAO-mediated trypanosome killing. Ammonia, an additional product of PAO-polyamine reaction, was not trypanocidal. Furthermore, the data suggested that less than 30 min exposure to the reaction mixture (and possibly to aminoaldehydes) was adequate to cause irreversible damage to trypanosomes.

Acrolein↗
PubMed1984

Mitogenicity of Naegleria fowleri extract for murine T lymphocytes.

The whole-killed pathogenic free-living amoeba, Naegleria fowleri, contained mitogenic activity (NFM) for mouse spleen cells. Similar preparations from the non-pathogenic amoeba N. gruberi and the pathogenic Acanthamoeba culbertsoni lacked mitogenic activity. Fluids from N. fowleri cultures, containing amoeba antigens, also failed to cause proliferation of mouse spleen lymphocytes. Spleen cells from athymic nude mice failed to respond to NFM. In addition, nylon wool non-adherent, but not the adherent, spleen cell subpopulation proliferated in the presence of NFM. These results show that the factor(s) is mitogenic for T lymphocytes. The spleen cells from mice treated with cyclophosphamide doses known to deplete T suppressor cell activity from this organ failed to respond to NFM, indicating that NFM may be mitogenic for T suppressor cells.

Amoeba↗
PubMed1984

Alterations in immunoglobulin synthesis by peripheral blood mononuclear cells from splenectomized patients with and without splenic regrowth.

Unstimulated and pokeweed mitogen (PWM)-stimulated immunoglobulin (Ig) synthesis by peripheral blood mononuclear cells (PBMC) in vitro, serum Ig concentrations, and the degree of splenic regrowth was studied in 33 patients who had been splenectomized following trauma. The concentration of IgG and IgA was significantly raised in the supernatants of unstimulated cultures of PBMC from the patients. The stimulation of Ig synthesis by PWM, measured as a stimulation index (SI), was significantly less in the culture of PBMC from the patients, compared with the controls. The SI was reduced both in those patients whose unstimulated PBMC secreted normal concentrations of IgG and IgA in culture, as well as in those whose cells secreted elevated concentrations of Ig. The concentration of IgM in the serum of the patients was significantly reduced compared with the controls, the serum IgG was raised, and the serum IgA was not altered. The degree of splenic regrowth (splenosis) was measured in the patients by splenic scanning, by using heat-damaged, radiolabeled autologous erythrocytes. The patients were allocated into four groups, depending on whether they had no (11 patients), minimal (11), moderate (seven), or large (four) splenosis. There was no difference between any of the groups with respect to the synthesis of IgG or IgA in culture or the serum Ig concentrations. These results indicate that Ig synthesis by PBMC in vitro, and serum Ig concentrations in vivo, are abnormal in patients who have been splenectomized for trauma, and that the generation of splenosis tissue does not correct these changes.

Adolescent↗
PubMed1983

Polyamine oxidase mediates intra-erythrocytic death of Plasmodium falciparum.

Using a number of established culture strains of Plasmodium falciparum, the effects of the addition of polyamine oxidase and spermine on the intra-erythrocytic forms were studied. Cultures to which polyamine oxidase and polyamines were added contained only degenerate parasites but if one or other were added alone the cultures were similar to the controls. The effects were confirmed by 35S-methionine incorporation.

Animals↗
PubMed1983

Site of expression of immunity to Naegleria fowleri in immunized mice.

An experiment was performed which confirmed a previous finding that mice are protected against Naegleria fowleri infection by immunization with amoeba-free supernatant from amoeba cultures. Histological observations suggested that this protection is expressed mainly at the nasal mucosa and possibly results from the combined effects of polymorphonuclear leucocyte-mediated killing of the amoeba and mechanical elimination of the organisms by extensive shedding of necrotic epithelium.

Amebiasis↗
PubMed1983

Alternative pathway activation of complement by African trypanosomes lacking a glycoprotein coat.

An in vitro culture Trypanosoma congolense cell line was established using the mammalian cell feeder layer system. One of the principle characteristics of this parasite was its ability to multiply in culture at 35 degrees C, as an uncoated trypanosome (lacking a glycoprotein surface coat) unlike the original blood stream form from which it was derived. This trypanosome was lysed when incubated in normal human serum in contrast to the parasite which possessed a surface coat. The lytic reaction as inhibited by EDTA but not EGTA and occurred in C2-deficient serum, demonstrating the involvement of the alternative pathway of complement activation. Similar results were obtained with procyclic forms of T. congolense and T. brucei brucei which also lacked surface coats. The results suggest that the glycoprotein surface coat protects the parasite by masking sites on the plasma membrane which are capable of promoting alternative pathway activation.

Animals↗
PubMed1983

Natural agglutinins to African trypanosomes.

Agglutinins to uncoated culture forms of the African trypanosomes, T. congolense and T.b. brucei were detected in sera from a variety of mammals not exposed to the parasites. The agglutinins in bovine serum were shown to be specific antibodies with opsonic properties selective for the species of trypanosome. These findings suggest a possible role for the glycoprotein coat in preventing access of cross-reacting antibodies to the plasma membrane of African trypanosomes.

Adult↗
PubMed1983

Inhibition of human polymorphonuclear leukocyte respiratory burst, bactericidal activity, and migration by pneumolysin.

The in vitro effects of pneumolysin, a sulfhydryl-activated toxin produced by Streptococcus pneumoniae, on various functions of human polymorphonuclear leukocytes (PMNLs) was investigated. Treatment of PMNLs with highly purified toxin significantly inhibited respiratory burst (in response to stimulation), ability to kill opsonized pneumococci, chemotaxis, and random migration. These inhibitions were observed at very low toxin doses (less than or equal to 1 hemolytic unit (2 ng) per 10(6) PMNLs), which had no effect on PMNL viability. These results suggest that pneumolysin could function in pathogenicity by interfering with the ability of PMNLs to migrate toward and kill pneumococci.

Bacterial Proteins↗
PubMed1983

Activation of the alternative pathway of complement by Acanthamoeba culbertsoni.

Normal human serum (NHS) contained an amoebicidal property for Acanthamoeba culbertsoni. Killing was quantitated by measuring the ability of the amoebae to undergo cell division subsequent to exposure to NHS, and also by microscopical examination. Plasma membrane disruption and extrusion of intracellular components occurred within 5-10 min following exposure to NHS. Adsorption of specific antibody did not remove the amoebicidal activity while heating serum at 56 degrees C/30 min or treatment with zymosan prevented the killing of A. culbertsoni. Haemolytic complement was consumed and C3 conversion occurred during the incubation of NHS with amoebae. Killing required the presence of the late complement components. The findings that (a) amoebae were killed in C2 deficient human serum and ethylene glycol tetra-acetic acid (EGTA), but not ethylenediamine tetra-acetic acid (EDTA) treated NHS; (b) haemolytic complement consumption, which occurred by incubating NHS with the amoebae, could be prevented by addition of EDTA, but not EGTA and (c) conversion of C3 occurred in the presence of EGTA, but not EDTA, indicated that activation of the alternative pathway of complement was involved. This may be of importance as a natural defence mechanism in humans against A. culbertsoni infections.

Amoeba↗
PubMed1982

A semi-automated microassay method for the measurement of ablastin, a division inhibitory antibody.

Division of Trypanosoma lewisi in the rat is terminated by ablastin, a factor(s) in the serum of rats acquired during infection which is believed to be specific antibody. In this study a semi-automated microassay technique for the measurement of ablastin is described. The system involved the use of [3H]TdR as a marker for trypanosome division and a multiple-well cell harvester to harvest trypanosomes from wells of microtitre plates. The method is versatile, quantitative and easy to perform, permitting the simultaneous measurement of numerous samples for this division-inhibitory activity.

Agglutination Tests↗
PubMed1982

Separation of mononuclear and polymorphonuclear leucocytes from human blood by the one-step Hypaque-Ficoll method is dependent on blood column height.

Further observations have been made in relation to separation of mononuclear (MN) and polymorphonuclear (PMN) leucocytes from human blood by the one-step procedure involving centrifugation of the blood on Hypaque-Ficoll medium. The distance separating the MN and PMN cell fractions was dependent on the height of the blood column but independent of the diameter of the tube, this distance being directly proportional to the height of blood. However, increasing the height of the blood column by diluting the blood in medium 199 did not increase the separation distance. Erythrocytes were shown to be important for separation of leucocytes into two distinct bands.

Cell Separation↗