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Biomedical subjects

J J Ballet

Publications and source records attributed to J J Ballet.

At least 73 records · Page 4Linked to original sources

The interferon compartment of the immune response in human malaria: I. Interferon inducers in Plasmodium falciparum cultures.

The present study concerns the interferon (IFN) compartment of the immune response in human malaria. It was undertaken with Plasmodium falciparum parasitized human red blood cell culture supernatants (PF-RBCS). Investigations were conducted in order to verify whether supernatants of such protozoa cultures had the capacity to induce gamma interferon previously identified in sera of P. falciparum infected patients and to verify whether a T-cell mitogen recently characterized in vitro could be correlated with the eventual IFN-inducing activity. Investigations were performed with nonsynchronized P. falciparum cultures and highly synchronized PF-RBC cycles. Results obtained with the first type of experiment demonstrated the presence of an immune interferon inductor in PF-RBCS controlled for their positive mitogenic activity. In supernatants from highly synchronized PF-RBC cycles it was possible to further correlate the mitogen activity with the capacity to induce IFN-gamma. Both activities were found in the time-interval situated near the end of the parasite cycle shortly previous of the merozoite stage. At an earlier time, at the peak of the ring stage, when no mitogen activity was detected, an interferon-induction activity, solely of IFN-alpha, was also demonstrated.

Cells, Cultured↗

The interferon compartment of the immune response in human malaria: II. Presence of serum-interferon gamma following the acute attack.

The present study concerns the monitoring of serum-interferon (serum-IFN) levels among 189 patients followed after and sometimes during an acute episode of malaria due mainly to Plasmodium falciparum (P. falciparum). Of these patients, 110 known to have no other parasitic or infectious disease were followed in France; 79 were from Thailand, among which 25 cases of neuromalaria were diagnosed. In a first four-month survey conducted in France, among 100 patients seen after the acute attack, serum-IFN-gamma was characterized among 87% cases for which at least two sera were controlled, whereas in a healthy population no serum-IFN was present. When efforts were concentrated on screening ten cases during the first 48 h of the febrile attack, serum-IFN-alpha was mainly characterized, whereas serum-IFN-gamma was present only once. Elevated leukocyte 2',5' oligoadenylate synthetase levels were found among several IFN-alpha positive patients of this study group. A peculiarity pertaining to the patients from Thailand was that one-third (25 cases) were cerebral malaria cases. Among these, 15 were followed under hospitalization during the first 96 h. In this study group, the onset of circulating immune interferon was found to be preceded or accompanied by that of IFN-alpha. Thus, if serum-IFN-gamma is largely characterized among malaria patients followed after the acute attack, it is possible that the onset of circulating immune interferon is generally preceded by that of IFN-alpha.

2',5'-Oligoadenylate Synthetase↗

Detection and characterization of serum antitrichomonal antibodies in urogenital trichomoniasis.

Antibodies against Trichomonas vaginalis were detected in serum samples from 98 patients by three immunological assays. A good correlation was observed between the enzyme-linked immunosorbent assay and the immunofluorescence method, whereas it was found that the enzyme-linked immunosorbent assay correlated better with the current or past detection of organisms than did other serological methods (immunofluorescence and hemagglutination). Similar results were obtained with whole trichomonads and two T. vaginalis soluble antigenic preparations, which suggests that immunodominant moieties shared by several T. vaginalis strains were detected. The level of antibodies of the immunoglobulin A class was higher in patients with past records of trichomoniasis, but less significantly so than the total antitrichomonal antibody level. Antibodies of the four immunoglobulin G subclasses were detected. Immunoglobulin G1 antibody values were higher in female than male patients.

Adolescent↗

Hypercalcemia in chronic myelogenous leukemia: evidence for excessive parathyroid hormone secretion.

Hypercalcemia was associated with osteolytic bone lesions in a 60-year-old woman with chronic myelogenous leukemia in the accelerated phase. Using highly specific antisera to parathyroid hormone, radioimmunoassays disclosed elevated levels of carboxyl-terminal (53-84) and intermediate (44-68) fragments. In addition, concomitant variations of serum calcium level and leukocyte counts, increased urinary c-AMP excretion, morphological integrity of parathyroid glands, and absence of bone resorbing activity in myeloblast culture supernatants are consistent with the hypothesis that the humoral hypercalcemia was due to the excessive production of PTH. This production may have been ectopic, although no PTH secretion was demonstrated in myeloblast culture supernatants.

Animals↗

Total and IgE antibody levels following booster immunization with aluminum absorbed and nonabsorbed tetanus toxoid in humans.

Total and IgE serum antibodies to tetanus toxoid were measured in 32 healthy adults, 3-4 weeks following booster immunization with either plain or aluminum hydroxide-absorbed tetanus toxoid. Whereas no difference in the total antibody values was observed, the level of anti-tetanus toxoid IgE antibodies was significantly higher in the group boostered with the adjuvanted vaccine.

Adult↗

Immunological evaluation of cell-mediated and humoral immunity in Thai patients with cerebral and non-cerebral Plasmodium falciparum malaria: I. Cutaneous delayed hypersensitivity, blood leukocytes and in vitro lymphocyte responses.

In Thai patients with acute P. falciparum malaria including cerebral cases, cell mediated immune functions were studied in vivo and in vitro. Initial cutaneous delayed reactions to phytohaemagglutinin and soluble protein antigens were negative in most cerebral malaria patients. No major alteration of the number of circulating T and B cells was observed. In lymphocytes cultures, proliferatives responses to lectins or protein antigens were generally found within normal ranges. This study shows a direct role of P. falciparum on the impairment of cell mediated immunity.

Adolescent↗

Immunological evaluation of cell-mediated and humoral immunity in Thai patients with cerebral and non cerebral Plasmodium falciparum malaria: II. Evolution of serum levels of immunoglobulins, antimalarial antibodies, complement fractions and alpha interferon.

In Thai patients with Plasmodium falciparum malaria, IgG and IgM values were elevated, whereas IgA levels were within normal ranges. No association of Ig values with parasitaemia was noted. IFA-IgM antibody levels were lower in cerebral malaria (CM) than in the non cerebral malaria (NCM) group. IFA-IgG antibodies were present in all patients. The mean C3 and C4 values were similar among patients from the CM and NCM groups. Interferon like activity was detected in all CM and NCM patients, and no correlation was found with either antimalarial antibodies, complement or parasitaemia.

Antibody Formation↗

Major histocompatibility complex restriction of tetanus toxoid-specific human T lymphocyte clones.

Peripheral blood mononuclear cells (PBMC) from an HLA DRw6/7 individual were stimulated with tetanus toxoid (TT). T cell blasts were cloned by the limiting dilution technique in the presence of TT and irradiated autologous PBMC (iPBMC). Twelve were propagated under interleukin 2 and restimulated weekly with TT and iPBMC. All proliferated specifically in response to TT or either the alpha or beta chain of the toxin molecule. HLA restriction of specific proliferative responses was analyzed using a panel of HLA-typed unrelated donors and selected families, and blocking experiments with anti-HLA class I and class II monoclonal antibodies (mAb). Three types of restriction were observed: (a) autologous restriction; the inhibition observed using anti-HLA DR mAb as well as family studies performed previously with a similarly restricted clone obtained from the same donor suggest an HLA DRw6-linked restriction; (b) an HLA DR7 restriction was found for 2 clones, specific for alpha or beta chain; the identical pattern of inhibition obtained with two different mAb belonging to the same cluster suggests that these clones may be restricted by the same (or a very close) epitope of the HLA DR7 molecule; (c) an unusual restriction pattern was found for one clone; PBMC from more than 80% of donors could present TT whatever their degree of HLA compatibility with the autologous donor. Family studies were unable to disclose any restriction with known class II (or class I) antigens. While no inhibition was observed with anti-DR or -DC reagents, a mAb that recognizes class I antigen when associated with beta 2-microglobulin did inhibit the proliferation of this clone.

Antibodies, Monoclonal↗

Specific immune responses after booster immunization with tetanus toxoid in man: study of kinetics, family segregation, and linkage to HLA of in vitro lymphocyte proliferative responses and serum-antibody responses.

Kinetics and family transmission of antigen-specific in vitro cell-mediated responses were investigated in 68, and serum-antibody responses to tetanus toxoid (TT) in 73 individuals from a total of 12 families. Proliferative responses to highly purified TT monomer were studied in 6- to 7-day lymphocyte cultures. The effect of booster immunization was detectable 7 (D7) and 30 (D30), but not 120 days (D120) later. The sex of donors was not found to have any influence. A significant influence of the time interval since the last immunization was found for the responses at D7 and D30. Data were correspondingly adjusted for segregation and linkage analyses. Several transmission hypotheses for the data obtained at D7 and D30 were evaluated by likelihood ratio tests. Observations at D30 were compatible with the hypothesis of a control by a dominant genetic determinant for high responses closely linked to the major histocompatibility complex region. No such evidence could be found for D7. After booster immunization, mean antibody levels determined on D7, D30 (peak of response), and D120 were found to be higher than those prior to immunization (D0). The sex of the donors was found to have no influence on antibody responses. The time interval since the last immunization and the age of donors both had a slight influence, and data were correspondingly adjusted for segregation and linkage analyses, which showed no evidence of genetic control of the antibody responses or of linkage to HLA.

Adolescent↗

Serum IgE and IgG antibodies to tetanus toxoid and candidin in immunodeficient children with the hyper-IgE syndrome.

Serum IgG and IgE antibodies directed against tetanus toxoid and candidin were measured using a solid-phase radioimmunoassay in seven patients with the immunodeficiency syndrome with hyper-IgE. In parallel, six normal children, three normal adults, and eight patients with or without elevated serum IgE (including atopic diseases, Candida infections, and active schistosomiasis) were studied. Serum IgG antibodies to tetanus toxoid and candidin were present in the hyper-IgE patients in concordance with their immunization history. High concentrations of IgE antibodies against both antigens were found in the immune hyper-IgE patients but not in the controls. This suggests that elevated IgE antibody responses in the hyper-IgE syndrome results from a primary defect of IgE class regulation rather than an abnormal or deficient antibody response.

Adolescent↗

Impaired cell-mediated immunity in Plasmodium falciparum-infected patients with high-parasitemia and cerebral malaria.

Several cell-mediated functions were studied in vivo and in vitro in 63 Thai patients with acute falciparum malaria, including 21 cases with cerebral manifestations and 10 cases with initial parasitemia over 10%. Initial delayed cutaneous reactions to phytohemagglutinin and soluble protein antigens were negative in most cerebral malaria cases. In other patients, skin reactions were impaired or abolished as a direct function of parasitemia. No major alteration in the numbers of blood T and B lymphocytes was found. In lymphocyte cultures, proliferative responses to lectins were generally found within normal ranges; in contrast, proliferative responses to candidin were suppressed in parallel with delayed cutaneous responses to the same antigen. From these data, it can be concluded that the alteration of specific cell-mediated responses are predominantly detectable in acute cases with major parasite invasion, i.e., high parasitemia and/or cerebral manifestations. A direct role of Plasmodium falciparum was further suggested by the rapid restoration of cell-mediated functions observed in several cases under successful antimalarial therapy. These results do not support any evidence in favor of a preexisting cellular immune deficiency in relation with the occurrence of cerebral or high-parasitemia acute malaria in these patients.

Acute Disease↗

[Genetic effect on specific human immune responses to tetanus anatoxin].

Kinetics and family transmission of antigen specific immune responses were investigated before and 7, 30 and 120 days after booster immunization with tetanus toxoid (TT) in 73 individuals from 12 families. The study of TT specific in vitro lymphocyte proliferative response and of TT antibody levels by radioimmunoassay were performed in parallel; the effect of booster immunization was detectable 7 and 30 days later and still 120 days later for antibody response. No influence of the sex of donors was found. Because of the significant influence on the level of responses of the time interval since last immunization, data were correspondingly adjusted for segregation and linkage analysis. Observations at day 30 were compatible with the hypothesis of control by a dominant genetic determinant for high proliferative responses closely linked to the major histocompatibility complex region.

Antibodies, Bacterial↗

Human T cell clones specific for tetanus toxoid: characterization of antigen specificity and HLA restriction.

T cell blasts isolated from six-day cultures of peripheral blood mononuclear cells stimulated with tetanus toxoid (TT) were cloned in a two-layer agar system in the presence of autologous irradiated PBM (iPBM) and TT. Colonies were individually isolated and expanded in interleukin 2-containing medium. The antigen specificity of three T cell clones was attested by their capacity to proliferate under restimulation by TT and not by an unrelated antigen. The clones were specific for either the alpha or the beta chain of the toxin. T cells from these clones expressed Ia determinants and antigens of the helper/inducer T cell subset as defined by anti-T monoclonal antibodies. In the case of the alpha chain-specific clone MA 11 from the donor MA, allogeneic iPBM from HLA-compatible unrelated donors, including seven donors sharing one HLA DR specificity with MA, were found inefficient as antigen-presenting cells. A familial study, however, demonstrated that antigen presentation could be obtained using nonautologous cells. The presenting capability of cells from relatives of the donor MA segregated in association with the HLA-DRw6-bearing maternal haplotype present in MA. Results suggest that MA 11 cells recognized the antigen in the context of a surface determinant closely linked to HLA-DRw6.

Animals↗

Effect of isoprinosine on in vitro proliferative responses of human lymphocytes stimulated by antigen.

Isoprinosine, a synthetic purine derivative, did not significantly interfere with the thymidine uptake of triggered normal lymphocytes, nor exhibit a detectable mitogenic activity. Isoprinosine was able to significantly enhance specific proliferative responses of human lymphocytes from sensitized donors to soluble antigens. Isoprinosine did not alter the early interaction of human mononuclear cells with 125I-labelled antigen, nor the expression of their membrane receptors for immunoglobulin Fc fragments. The agent could not replace the accessory rôle of adherent cells in proliferative responses to antigens. The enhancing effect of isoprinosine on antigen specific responses of T-cells was observed upon adding the compound on any one of the seven days of culture. Isoprinosine partially restored the inhibited proliferation of lymphocytes cultured in the presence of deoxyadenosine and deoxycoformycin. Data suggest that metabolic changes involving purines may account for the effect of isoprinosine on the expression of T-cell responses.

Adult↗