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Biomedical subjects

A Ferrante

Publications and source records attributed to A Ferrante.

At least 199 records · Page 11Linked to original sources

Elevated natural killer (NK) cytotoxicity of mononuclear leucocytes from splenectomized patients: increase in Leu-7+ and Leu-11+ leucocytes.

The natural killer (NK) cell cytotoxic activity (against K562 targets) of peripheral blood mononuclear leucocytes (MNL) from patients splenectomized for trauma was examined. The data were fitted to a mathematical model from which the values for maximal cytotoxicity, and the number of MNL required to achieve 25% cytotoxicity (LD25-, were computed. The results showed that the NK cell cytotoxicity of MNL from splenectomized patients was significantly elevated at all effector/target cell ratios tested (1:1 to 100:1), compared to normal subjects. In the splenectomized group there was a significant increase in the maximal cytotoxicity and a significant reduction in the LD25. Flow cytofluorometry studies revealed an increase in percentage and absolute numbers of cells bearing Leu-7 or the Leu-11 antigens in MNL of splenectomized patients. We found that there was a significant correlation between the percentage of Leu-11+ cells and the NK cytotoxicity (both maximal and LD25) but not between Leu-7+ and these parameters, for both the controls and splenectomized subjects. This suggests that the increased NK cytotoxicity by the MNL of splenectomized patients may be due wholly or partly to an increase in the proportion of cells expressing the Leu-11+ antigens.

Adult↗

Inhibition of human monocyte respiratory burst, degranulation, phospholipid methylation and bactericidal activity by pneumolysin.

The interaction between the pneumococcal toxin pneumolysin and human monocytes was examined. At non-cytotoxic concentrations (0.5-2.5 HU/10(6) cells) pneumolysin depressed the oxygen-dependent respiratory burst in monocytes, induced by opsonized zymosan or phorbol myristate acetate (PMA). This included depressed hexose-monophosphate shunt activity and hydrogen peroxide production. The toxin also depressed the ability of monocytes to degranulate (measured by release of lysozyme) in response to the above stimuli. Phospholipid transmethylation was also markedly decreased by pretreating monocytes with pneumolysin. These effects on monocyte functions were accompanied by a decreased ability of pneumolysin-treated monocytes to kill Streptococcus pneumoniae, the organism that produces the toxin. Cholesterol, which inhibits the haemolytic activity of the toxin, was shown to abrogate the effects of pneumolysin on monocytes.

Bacterial Proteins↗

Selective inhibition of the in vitro murine B lymphocyte response by pentamidine.

A study was undertaken on the immunomodulating properties of pentamidine, a diamidine used in the treatment of African trypanosomiasis, pneumocystosis and leishmaniasis. Pentamidine inhibited the ability of mouse splenic lymphocytes to respond to mitogens. In particular inhibition of the B lymphocyte response was observed. At concentrations of 1 microgram/ml (1.7 x 10(-6) M), pentamidine markedly inhibited the response to the B cell mitogen, lipopolysaccharide (LPS), while concentrations of 10 micrograms/ml had to be attained to produce a similar effect on the response to the T cell mitogens phytohaemagglutinin (PHA) and concanavalin A (ConA). Further studies showed that pentamidine was not toxic to either resting or proliferating cells and probably acts by interacting directly with B cells rather than modifying the regulatory cell populations.

Amidines↗

Elevated natural killer (NK) cell activity: a possible role in resistance to infection and malignancy in immunodeficient splenectomized patients.

Splenectomized patients, who have had their spleens removed following trauma, have immune deficiencies. However, the risk of infection (with one exception--septicaemia caused mainly by Streptococcus pneumoniae) and malignancy in these patients appears to be comparable to that of healthy individuals. We propose that a compensatory increase in the activity of effector cells, such as natural killer cells (NK) and macrophages, may protect against infection and malignant diseases in splenectomized individuals.

Adolescent↗

Trypanolytic activity, agglutinins, and opsonins in sera from animals refractory to Trypanosoma lewisi.

An examination of sera from a range of animals refractory to Trypanosoma lewisi showed that some contain trypanolytic activity and agglutinins for this trypanosome. Trypanolytic activity was demonstrated in bovine, sheep, and rabbit serum. These sera were shown to also contain agglutinins. The trypanolytic activity in all three sera was abolished by heat inactivation at 56 degrees C for 30 min. Studies with bovine serum showed that the lytic activity was totally inhibited by the addition of EDTA but was only partially inhibited by ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid-Mg2+, suggesting the involvement of both classical and alternate pathways of complement activation. Serum from the natural host, the rat but not mouse serum, was capable of inhibiting the trypanolytic activity of bovine serum. The agglutinins in bovine serum were specific, since they could be adsorbed out with T. lewisi but not T. musculi. They fractionated on gel filtration in the position expected for 19S antibodies. By using opsonization measuring techniques, it was found that mouse serum lacked opsonins to T. lewisi, although opsonic activity was detectable in human serum. The absence of agglutinins, trypanolysins, and opsonins in mouse serum suggests that other factors prevent the infection of mice by T. lewisi. From these findings, it would appear that the inability of T. lewisi to infect a range of mammals, with the exception of mice, could be due to the presence of antibodies, the ability to activate complement through the alternative pathway, or both. The absence of these recognition factors and the ability to evade the effects of alternative pathway activation may be important factors in the ability of this parasite to establish infections in rats.

Animals↗

Changes in intestinal fluid and mucosal immune responses to cholera toxin in Giardia muris infection and binding of cholera toxin to Giardia muris trophozoites.

The effect of Giardia muris infection on the diarrheal response and gut mucosal antibody response to cholera toxin was examined in mice. The results obtained showed that the fluid accumulation in intestinal loops exposed to cholera toxin was increased in mice infected with a low number (5 X 10(4) ) of G. muris cysts compared with the response in noninfected mice. This effect was associated with a marked reduction in absorption of oral rehydration fluid from the intestine. In contrast, mice infected with a high dose (2 X 10(5) ) of cysts showed a marked decrease in fluid accumulation in response to the toxin. This decrease might be related to the finding that both G. muris and Giardia lamblia trophozoites can bind significant amounts of cholera toxin. Evidence is presented which suggests that the gut mucosal antibody response, mainly immunoglobulin A but also immunoglobulin G, to an immunization course with perorally administered cholera toxin was depressed in mice infected with G. muris. The reduction in antibody levels was particularly evident when the primary immunization was made very early after infection. The serum antitoxin antibodies to the oral immunization with cholera toxin were, however, not affected. Likewise, the delayed-type hypersensitivity response against sheep erythrocytes in animals primed subcutaneously with sheep erythrocytes was not modified during the course of G. muris infection.

Animals↗

Inhibition of human neutrophil locomotion by the polyamine oxidase-polyamine system.

The polyamines, spermine and spermidine, in the presence of either bovine serum [containing polyamine oxidase (PAO) activity] or partially purified PAO, inhibited human neutrophil locomotion. This effect could not be produced by either bovine serum, PAO, or the polyamines alone. The results suggested that at least two of the products generated during the oxidation of polyamines by PAO, namely H2O2 and ammonia, are not responsible for the effects on neutrophils. Acrolein, a breakdown product of other products (aminoaldehydes), was found to inhibit the neutrophil functions. Since polyamines, and possibly PAOs, accumulate at inflammatory sites, products of the PAO-polyamine reaction could function as regulators of the inflammatory response.

Acrolein↗

Amoebicidal activity of the antifungal antibiotic sinefungin against Entamoeba histolytica.

The antifungal antibiotic sinefungin, a potent inhibitor of methyl transferases and a potential inhibitor of polyamine biosynthesis, exhibited marked cytolytic activity against Entamoeba histolytica in vitro with respect to all the amoeba strains tested. Strains of high and low virulence displayed equal sensitivity to the antibiotic. Minimal Amoebicidal Concentration was 5 to 10 micrograms/ml.

Adenosine↗

Immunization with killed Acanthamoeba culbertsoni antigen and amoeba culture supernatant antigen in experimental Acanthamoeba meningoencephalitis.

Mice immunized with killed (sonicated) Acanthamoeba culbertsoni A-1 antigen displayed marked resistance to intranasal challenge with the amoeba. A primary immunization produced a survival rate of approximately 40%, and survival values of greater than 80% were obtained by multiple immunizations. Similarly mice immunized with fluids from A-1 cultures were highly resistant to infection.

Amebiasis↗

Enhancement of base hexose-monophosphate shunt activity of human polymorphonuclear leucocytes by human beta-interferon.

The effect of human fibroblast interferon (HuIFN-beta) on the HMP shunt activity of human polymorphonuclear leucocytes (PMNLs) was examined. HuIFN-beta caused an increase in the base level of the HMP shunt activity. No significant increase was observed in the same PMNLs stimulated with opsonized zymosan. The augmentation of this property, generally associated with antimicrobial and cytotoxic properties of the PMNLs, may be of potential importance in host defences against microbial and malignant diseases.

Humans↗

In vitro inhibition of natural killer cell activity by doxycycline.

The effect of four tetracyclines, tetracycline, rolitetracycline, oxytetracycline and doxycycline, on human natural killer (NK) cell-mediated cytotoxicity was examined in vitro. Doxycycline was the only tetracycline which inhibited the NK cell activity. At concentrations of 10 micrograms/ml the drug caused approximately 50% inhibition of NK cell mediated cytotoxicity against K562 target. The inhibition was not a result of a toxic effect of the drug on NK cells. These results support the previous findings that doxycycline shows immunosuppressive properties.

Cell Line↗

Modification of polymorphonuclear leucocyte function by imidazoles.

The effect of five imidazole derivatives (metronidazole, tinidazole, clotrimazole, miconazole and ketoconazole) on human polymorphonuclear leucocytes (PMNL) was examined in vitro. Metronidazole and tinidazole had no apparent effect on either PMNL chemotactic response or PMNL fungal/bacterial killing. In contrast, clotrimazole, miconazole and ketoconazole inhibited PMNL chemotaxis. In addition, miconazole and ketoconazole were shown to depress the ability of PMNL to kill bacteria and fungi.

Blood Bactericidal Activity↗

Cutaneous horn.

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Female↗

The role of natural agglutinins and trypanolytic activity in host specificity of Trypanosoma musculi.

Trypanolytic activity and agglutinins for T. musculi were demonstrated in sera from refractory hosts. The agglutinins in human and bovine serum were specific antibodies. The trypanolytic activity was a result of the ability of the trypanosomes to activate complement in these normal sera. The results suggested that Trypanosoma musculi activates human complement by the alternative pathway. The activity was inhibited by EDTA but not EGTA, and trypanosome lysis occurred in the absence of C2. In addition, conversion of C3 occurred in the presence of EGTA. The trypanolytic activity of bovine serum was similarly inhibited by EDTA but not EGTA. Trypanosome lysis failed to occur in C6 deficient rabbit serum, showing that the late components of complement are required for parasite lysis. Trypanosome lysis by human or bovine serum was inhibited by the addition of mouse serum but not rat serum. These observations suggest that the presence of trypanolytic activity and antibodies to this trypanosome in sera of normal mammals may be responsible for the restricted host range of the trypanosome, and that the absence of these antibodies and the ability of this parasite to evade the trypanolytic activity enables T. musculi to establish infections in the mouse.

Agglutination Tests↗

The effect of anti-malarial drugs on human natural killer cells in vitro.

Human natural killer (NK) cell cytotoxicity against K-562 target was found to be markedly depressed by quinacrine, mefloquine, pyrimethamine and chloroquine. The most potent were quinacrine and mefloquine. Two other drugs tested, quinine and primaquine, displayed no significant effects even after long incubation periods with effector cells. The results showed that the inhibitory effects were not related to an inhibition of effector cell binding to target or to a toxic effect on NK cells.

Antimalarials↗

Polyamine oxidase-mediated intraerythrocytic killing of Plasmodium falciparum: evidence against the role of reactive oxygen metabolites.

The polyamines spermine and spermidine, in the presence of polyamine oxidase, were shown to be cytotoxic in vitro to various isolates of Plasmodium falciparum. Neither polyamines nor polyamine oxidase alone was cytotoxic. This cytotoxicity was manifested by the degeneration of the parasites into crisis forms and by the inhibition of methionine incorporation by the parasites. Only 2 to 2.5 h of exposure to the reaction mixture (polyamine oxidase, 100 micrograms/ml; spermine, 1 mM) resulted in parasite death. It was shown that ammonia, hydrogen peroxide, and associated reactive oxygen intermediates produced during the oxidation of polyamines were not the cause of the parasite death observed in this system. This suggested that aldehydes or further breakdown products of these, e.g., acrolein (or both), need to be considered as the effector substances of the polyamine oxidase-mediated killing of P. falciparum.

Animals↗

Activation of human complement by the pneumococcal toxin pneumolysin.

Highly purified pneumolysin (at a concentration of 10 micrograms/ml) caused significant activation of human complement, as measured by conversion of C3. Complement activation in the presence of pneumolysin was not observed in sera chelated with a combination of Mg2+ and ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid, and activation was only slight in C2-deficient sera. This suggests that the toxin is capable of activating the classical complement pathway. Treatment of normal human serum with pneumolysin also significantly reduced its opsonic activity for Streptococcus pneumoniae.

Bacterial Proteins↗