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Biomedical subjects

D Frommel

Publications and source records attributed to D Frommel.

At least 37 records · Page 2Linked to original sources

Interactions between the human monocytic leukaemia THP-1 cell line and Old and New World species of Leishmania.

The human promyelocytic THP-1 cell line has been found to support the growth of Leishmania parasites. THP-1 cells, differentiated with retinoic acid, cease replication while remaining in suspension. 72 +/- 8% of THP-1 cells became infected after inoculation with promastigotes of several Old and New World Leishmania species. The resulting amastigotes (19 +/- 5 per infected cell) were easy to harvest, capable of reinfecting cultures of normal human cells and, in the case of L. major and L. infantum, caused specific lesions in BALB/c mice. This culture system should facilitate biochemical and immunological studies on amastigotes and be of use in screening anti-parasite drugs.

Animals↗

BCG: a modifier of immune responses to parasites.

The use of BCG (Bacille Calmette-Guerin) as an adjuvant is well-established for vaccination against leprosy and tuberculosis. Dominique Frommel and Phillippe Lagrange discuss the effects of BCG in the control of parasite infections, particularly leishmaniasis, and the possibility of the development of anti-parasite recombinant BCG vaccines.

Journal Article↗

Vaccination trial against canine visceral leishmaniasis. Phocean Veterinary Study Group on Visceral Leishmaniasis.

In a double-blind study 393 seronegative dogs, residing in a holoendemic area for Leishmania donovani infantum infection, were randomly assigned to an immunization with a partly purified L.d. infantum-derived preparation, or received adjuvant only. During the first year of the study period the rate of infection was significantly higher in the vaccinated group than in the control one (P less than 0.05), but this difference disappeared during the second year (P = 0.44). Since a similar immunization protocol conferred resistance against experimental murine leishmaniasis, these results stress the differences that may exist between the natural hosts of Leishmania parasites and experimental animal substitutes.

Animals↗

[Large-scale production of amastigotes by a human monoblastoid cell line].

In this study, a human monoblastoid cell line (TPH-1) was tested in vitro for the production of Leishmania amastigotes. The number of TPH1 cells increased with time and 6 days after promastigote infection the percentage of infected cells was around 45%. Pre-treatment of TPH1 cells with retinoic acid induced the cells to differentiate into unreplicating macrophage-like cells. Ninety per cent was parasitized 6 days after promastigote infection; the number of amastigotes quintuplied during this period of time; this result was irrespective of the Leishmania species used for experiments. Viable and infective parasites were obtained from treated and nontreated cells. TPH1 cells merit further consideration for research concerning new molecules active against Leishmania.

Animals↗

Inoculation of BALB/c mice against Leishmania major infection with Leishmania-derived antigens isolated by gel filtration.

Gel filtration can be used as a substitute for preparative polyacrylamide gel electrophoresis in the preparation of an immunogenic, partly purified, fraction isolated from lysates of Leishmania promastigotes. This fraction, the molecular weight of which ranged from 70,000 to 53,000, when administered to BALB/c mice in associated with muramyl dipeptide induced resistance against cutaneous leishmaniasis.

Animals↗

Factor VIII procoagulant antigen in human tissues.

The localization of factor VIII procoagulant antigen (VIII:Ag) and factor VIII von Willebrand antigen (VWF:Ag) was investigated in human liver, lung, spleen, placenta and umbilical cord, by an immunoperoxidase technique using an avidin biotin complex (ABC). Positive staining for VIII:Ag was observed in the endothelial cells of liver sinusoids, veins and arteries, as well as in the endothelial cells of placenta, lung and spleen. VWF:Ag was detected in the vascular endothelial cells of all the organs explored. The staining intensity of both VIII:Ag and VWF:Ag varied in the different tissues and showed a distinctive pattern of distribution in the liver. VIII:Ag was also observed in the cytoplasm of dysplastic, foetal-like hepatocytes which infiltrated one liver specimen. Our results agree with the view that liver endothelial cells are a major site of Factor VIII (F VIII) storage and secondary release into the circulation. However, the bright staining intensity of VIII:Ag and VWF:Ag in the lung and placenta suggests that these two tissues might also be a substantial source of F VIII.

Antigens↗

In vitro assessment of anti-Leishmania immunity of man acquired with a vaccine.

Monocytes, obtained from a human volunteer immunized with a Leishmania infantum-derived vaccine, when cultured in vitro displayed a strong parasiticidal activity against L. major promastigotes. In addition, immune serum conferred leishmanicidal activities to monocytes of normal, unexposed donors, and to murine macrophages.

Animals↗

Vaccination and treatment trials against murine leishmaniasis with semi-purified Leishmania antigens.

Antigens with molecular weight ranges of 94-67 kDa (LiF2), 30-20 kDa (LiF5), or below 20 kDa (LiF6), isolated from lysates of Leishmania infantum promastigotes by electroelution from polyacrylamide gels were injected into mice which were genetically either partially resistant (C57BL/6) or susceptible (BALB/c) to Leishmania infection. One month after the completion of the intravenous (C57BL/6) or subcutaneous (BALB/c) schedules, the mice were challenged with 1 x 10(3) L. major promastigotes. All mice immunized with LiF2, LiF5 and LiF6 were completely resistant. Furthermore, the C57BL/6 mice immunized with LiF2 resisted a second challenge with 1 x 10(4) L. major amastigotes. 5 months later, LiF2 antigen was used for immunotherapy of L. major leishmaniasis; parasites disappeared from the treated skin lesions, although ensuing systemic infection could not be averted.

Animals↗

Immunization of dogs with a Leishmania infantum-derived vaccine.

A partially-purified extract of Leishmania infantum has been administered to healthy dogs. Post-immunization sera were found to neutralize the infectivity of L. infantum and to abate the development of L. major. Muramyl dipeptide and one of its derivates, murabutide, were the best adjuvants.

Adjuvants, Immunologic↗

Vaccine-induced immunity against cutaneous leishmaniasis in BALB/c mice.

Partially purified antigens, derived from Leishmania infantum or L. major promastigotes and isolated under reducing conditions, were used to immunize BALB/c mice. Three subcutaneous injections of the 64- to 97-kilodalton preparation in conjunction with muramyl dipeptide conferred long-lasting immunity against L. mexicana subsp. mexicana and L. major infection; they led to the development of antibodies neutralizing the infectiousness of promastigotes, induced specific delayed-hypersensitivity reactions, and generated populations of peritoneal macrophages capable of killing amastigotes. Vaccination resulted in no harmful effects, since these antigen neither exacerbated preexisting Leishmania infection nor impeded the formation of antibodies to other antigens administered concomitantly.

Animals↗

[Needle aspiration biopsy in the diagnosis of cutaneous leishmaniasis].

The classic diagnostic procedure for cutaneous leishmaniasis is based on the examination of Giemsa-stained smears made from the fluid obtained by scraping the edges of the lesion with a lancet, or prepared with small plugs of superficial tissues. In this report, we compare the results given by this standard method with those obtained by the examination of needle aspirates. Aspirates are secured by injecting a few millimetres outside the external border of the lesion 0.3 to 0.5 ml of saline through a thin needle, rubbing the injured skin, and thereafter pulling back slowly the plunger. Amastigotes were found in all smears from needle aspirates, and in only 11 out 15 obtained by scraping. Aspirates were also more suitable for cultures of parasites.

Adult↗

High affinity human monoclonal antibodies directed against hepatitis B surface antigen.

Peripheral blood mononuclear cells from donors immunized with hepatitis B vaccine (Pasteur Hevac B) were transformed with Epstein-Barr virus. Two polyclonal cell lines, producing antibodies to hepatitis B surface antigen were established and cloned. Seven clones were isolated; they secreted between 10 and 20 micrograms/ml of HBs specific IgG1 kappa or lambda antibody with anti-HBs titer of 300-800 IU/ml. These human antibodies expressed the anti 'a' specificities and had high affinity and avidity; their potential use as reagents for hepatitis B virus detection and for passive immunotherapy is under study.

Antibodies, Monoclonal↗

The role of HIV infectivity and composition of factor VIII concentrates on the immunity of haemophiliacs positive for HIV antibodies.

Forty-six subjects (44 HIV antibody-positive) with some degree of immune deficiency (at least TH/TS ratio below 1) were randomly distributed into 4 treatment groups. Each group was assigned to 1 of 4 products to be used exclusively for a 1-year period: 1 concentrate was of intermediate purity and not heat-treated, and 3 were heat-treated in order to inactivate HIV, 2 of them being of higher purity. At 4-6-month intervals, check-ups, including as markers clinical examination, platelet, lymphocyte and T cell subset counts, IgG levels and delayed hypersensitivity test, were carried out. At entry as well as at the end of the study, groups were not statistically distinguishable. No intra- nor inter-group differences were demonstrable for any of the markers. In contrast, using a scoring system for each marker and the results of check-up at entry as reference, significant differences between groups appeared on subsequent check-ups. Patients receiving intermediate-purity factor VIII, whether heat-treated or not, were mostly steady, while groups receiving heat-treated concentrates of a higher purity significantly worsened. This surprising outcome was no related to differences in anti-HIV titers or specificities. From this study, the potential long-term predictive value of this scoring system could not be established.

Acquired Immunodeficiency Syndrome↗