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Biomedical subjects

E Falcoff

Publications and source records attributed to E Falcoff.

105 records · Page 6Linked to original sources
PubMedDate not supplied

Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis following the combined administration of interferon-gamma and pentavalent antimonial compounds.

In an open trial, longer courses of pentavalent antimonials (Sbv) at sub-optimal doses (10 mg/kg body weight), in association with recombinant human interferon-gamma (IFN-gamma) (100 micrograms/m2 of body surface area) were administered, by daily intramuscular injections, to 13 patients with diagnoses of cutaneous or mucocutaneous leishmaniasis unresponsive to Sbv. Four patients presented with large skin ulcers, and 9 had mucosal involvement as the main manifestation, the latter affecting the nose (3 cases), nose and septum (2 cases), nose and oral cavity (1 case), and nose, pharynx and larynx (3 cases). Except for one case with severe involvement of the upper respiratory tract, the lesions were fully resolved by the end of therapy (mean duration 40 +/- 12 [SD] d, range 30-60 d) in the 11 patients who completed therapy. The main side effects were headache and fever (7 cases), together with leucopenia and eosinophilia (4 cases). It is concluded that combined administration of low doses of Sbv plus IFN-gamma may provide a novel therapeutic approach for the treatment of antimony-resistant cutaneous or mucocutaneous leishmaniasis. The possible mechanisms by which IFN-gamma contributes to resolution of the disease are discussed.

Adolescent↗
PubMedDate not supplied

The effector function of platelets is induced and regulated by T lymphocytes.

The demonstration of effector functions of platelets in parasitic diseases raised the question of their possible regulation by T lymphocytes. Normal human platelets, treated with culture supernatants from antigen- or mitogen-stimulated CD4+/CD8- T cells, developed the capacity to kill young larvae of Schistosoma mansoni, in the absence of antibodies. The presence of IFN gamma in the lymphocyte supernatants, the neutralization by monoclonal anti-IFN gamma antibody, and the direct inducer effect of recombinant IFN gamma, clearly identify this lymphokine as one of the stimulator factors. In contrast, ConA- and antigen-stimulated human CD8+/CD4- T-cell supernatants contained a factor able to inhibit the IgE-dependent platelet cytotoxicity toward the same targets. The production of oxygen metabolites by IgE-coated platelets stimulated by anti-IgE was also strongly inhibited by this lymphokine. This platelet activity suppressive lymphokine (PASL) was identified as a polypeptide of 15 to 20 Kd with a pI of 4.6. The in vivo relevance of PASL was demonstrated by the complete abolition, after PASL treatment, of the protection normally conferred following a challenge infection by intravenous passive transfer of platelets from immune to normal rats.

Adult↗
PubMedDate not supplied

Interferon induction by Lactobacillus bulgaricus and Streptococcus thermophilus in mice.

This study investigates the effect of intraperitoneal injection of L. bulgaricus and S. thermophilus on interferon production by Swiss mice. The serum from mice given 5 x 10(7) L. bulgaricus in 0.5 ml saline showed a maximal production of 300 U/ml of alpha/beta interferon activity six hours after injection. Cellular integrity appears to be necessary for stimulation; heat-treated bacteria had little effect, while irradiated-bacteria had a greater effect. TNF was also produced, the sera of mice with high IFN also contained 300 U/ml TNF. Streptococcus thermophilus produced no detectable increase in serum IFN, but the 2'-5' A synthetase activity of peritoneal cells was elevated suggesting that small amounts of interferon were produced. Injection of Streptococcus thermophilus plus Lactobacillus bulgaricus did not change the serum interferon response to L. bulgaricus. These observations suggest that non-pathogenic bacteria such as those used in food processing, can stimulate IFN production in mice. There is some evidence that the bacterial cell walls might be responsible for at least part of this effect.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

In vivo and in vitro induction of (2'-5') oligoadenylate synthetase by human interferons in leukocytes from healthy donors and patients with renal cancer and hairy cell leukemia.

The effect of in vivo administered interferon-alpha (IFN-alpha) on 2-5-oligoadenylate (A) synthetase activity of peripheral blood mononuclear cells (PBMC) was compared in patients with hairy cell leukemia and renal cell cancer. Basic levels of this enzyme varied from donor to donor, but mean levels were not significantly different in patients with renal cell cancer or hairy cell leukemia compared to healthy donors. After a single injection of 3 x 10(6) IU IFN, these basic levels rose 2- to 8-fold within 12-24 h post-injection and reverted to pretreatment levels after 48 h. The extent of this in vivo stimulation by IFN-alpha was similar in patients with hairy cell leukemia and renal cell carcinoma, and was correlated with down-regulation of IFN-alpha receptors. The in vitro effects of IFN-alpha, -beta and -gamma were compared after 18 h treatment with 10, 10(2) and 10(3) IU/ml of each IFN. Unlike IFN-alpha and -beta, IFN-gamma did not induce 2-5 A synthetase activity in either normal PBMC or hairy cells; these results were related to the effects of the three IFN on proliferative response of normal PBMC to phytohemagglutinin. Our data support the idea that 2-5 A synthetase activity is a marker of biological response to interferon treatment in human cancers.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

Affinity chromatographic analysis of murine interferons induced by viruses and by T and B cell stimulants.

Murine interferons induced by viruses and by non-viral substances such as lectins, tilorone, lipopolysaccharide and Brucella have been analysed by affinity chromatography on a column of Sepharose coupled to antiviral interferon antibodies. The results reported here suggest that virus and B-cell stimulants induced interferons which are antigenically related and that T cell-dependent mitogens induce and "interferon like" molecule which appears to be antigenically and physiocochemically different.

Animals↗
PubMedDate not supplied

Enhancement of mouse natural killer cell activity by type II interferon.

It is likely that interferons are key molecules in the physiological regulation of natural killing (NK) activity. This assumption is based on the strong enhancing effect exerted by type I interferon on NK cells. The aim of this study was to examine whether type II interferon, released upon activation of T lymphocytes by a mitogen, had the same enhancing effect. Crude PHA-induced interferon was purified on affinity chromatography columns (Blue Sepharose), and the eluted fractions were tested in parallel for antiviral activity and for in vitro boosting effect on spleen cell natural cytotoxicity. We found that both activities were unseparable. Acid pretreatment of purified type II interferon, as well as addition of anti-type II interferon serum, greatly decreased the enhancement of the spleen cell cytotoxic response. Responder cells to type II interferon are NK cells (surface Ig-negative, Thy-1-negative, devoided of acid Fc receptors) as assessed by classical spleen cell fractionation procedures based on cell surface markers. Comparison between the dose-response curves obtained with type I and type II interferons suggest that both interferon preparations stimulate NK activity in a comparable manner. We could conclude that interferon molecules (type I as well as type II) display a positive immunoregulatory function on NK cells.

Animals↗
PubMedDate not supplied

Inhibitory effect of interferon on DNA and RNA synthesis in murine spleen cells stimulated by lectins.

Spleen cells from mice inoculated with partially purified preparations of interferon (Sp. Act. 1 X 10(7) i.u./mg protein, 0.2 ml i. v./mouse) were stimulated in vitro with phytohemagglutinin, concanavalin A or lipopolysaccharide. After 2 days of stimulation, the incorporation of 3H-thymidine into TCA-insoluble radioactivity was inhibited 50-90% when compared with cells from animals inoculated with mock interferon. Maximal inhibition, with optimal doses of lectins was obtained when interferon was;inoculated 18 hours before. This effect of interferon on DNA synthesis was preceeded by inhibition of the incorporation of 3H-uridine into TCA-insoluble material. When cells were pretreated in vitro with interferon for 24 hours and subsequently stimulated with PHA, RNA synthesis was inhibited by 30-40%, whatever was the dose of the mitogen. The synthesis of 4S tRNA, 18S and 28S ribosomal RNAs were inhibited to the same degree by interferon. The incorporation of methyl groups into cytoplasmic sRNA was unaltered.

Animals↗