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Biomedical subjects

J de Saint Martin

Publications and source records attributed to J de Saint Martin.

At least 19 recordsLinked to original sources

Human immunodeficiency virus infection and AIDS in a person with negative serology.

A 38-year-old woman resident of Ivory Coast died of AIDS, while remaining human immunodeficiency virus (HIV)-seronegative. She had been regularly tested because her husband was HIV-seropositive. The subject's lack of specific antibodies was assessed using commercial tests and confirmed by a radioimmunoprecipitation assay of the patient's virus. She was unquestionably HIV-1-infected, with a high plasma virus load, and her virus could be isolated. Molecular analyses indicated this retrovirus was clade A, which is common in Africa, and it was highly homologous to the virus isolated from her husband. The subject's seronegative status was thought to be due to rapid depletion of specific CD4+ helper T cells, resulting from accelerated disease progression, and was host-related rather than due to a specific HIV strain.

Acquired Immunodeficiency Syndrome

Pharmacokinetics of R 82913 in patients with AIDS or AIDS-related complex.

R 82913, a tetrahydroimidazobenzodiazepinthione (TIBO) derivative with potent activity against human immunodeficiency virus 1 (HIV-1) in vitro, was given to 22 patients with AIDS or AIDS-related complex in a dose-escalating pilot study. Doses of 10 to 300 mg administered daily by intravenous infusion were well tolerated for up to 50 weeks, with no haematological or biochemical evidence of toxicity. Mean OKT4 cell count rose slightly during the second month of treatment when higher steady-state plasma concentrations of the drug were achieved. Median p24 antigen concentration fell by 41% during the first month of therapy. When the rise in p24 antigen before therapy was compared to the fall during treatment, end-point analysis showed a significant difference (p less than 0.03). The combination of potent antiretroviral activity in vitro and the observed effect on HIV p24 antigen and absence of toxicity in vivo indicate that R 82913 and related TIBO derivatives merit further study in the treatment of retroviral infections.

AIDS-Related Complex

Serum levels of IL-2, IL-1 alpha, TNF-alpha, and soluble receptor of IL-2 in HIV-1-infected patients.

Serum levels of the interleukins (IL-1 alpha, IL-2), tumor necrosis factor-alpha (TNF-alpha), and soluble receptor of IL-2 (sIL-2R) were studied by enzyme-linked immunosorbent assay (ELISA) in 12 normal healthy controls and 52 HIV-1 seropositive patients. Results indicated that: (1) sIL-2R levels were significantly increased in most HIV-1 seropositive patients. This increase appeared to be correlated with low CD4 cell counts and with the presence of detectable levels of p25 antigen. Furthermore, initially high levels of sIL-2R appeared to be correlated with progression of disease. (2) IL-2 levels were found to be increased in about 43% of asymptomatic carriers (ASY) and subjects with lymphoadenopathy-associated syndrome (LAS) compared with 12% in the case of AIDS-related complex (ARC) and AIDS patients. (3) There was a positive correlation between serum levels of TNF-alpha and IL-1 alpha in nearly all patients. Detectable levels of both cytokines were found in 34% of ASY and LAS patients and only rarely were detectable in ARC and AIDS patients. (4) Sixteen patients in whom progression of disease was observed were studied initially and at the moment they upstaged. No significant modification of serum levels of the three cytokines and sIL-2R studied could be evidenced. It was concluded that sIL-2R could be a useful marker of disease activity and progression, though a prospective study is necessary. For IL-2, IL-1 alpha, and TNF-alpha, this study indicated the presence of variable alterations in serum levels in HIV-1-infected patients.

AIDS-Related Complex

Detection of anti-Epstein-Barr virus trans-activator (ZEBRA) antibodies in sera from patients with human immunodeficiency virus.

Patients with AIDS and AIDS-related complex often show symptoms of Epstein-Barr virus (EBV) reactivation. Several EBV-encoded trans-acting factors activate the EBV lytic cycle, and one, ZEBRA (BamHI Z EBV replication activator; also called EB1), switches EBV from its latent to productive cycle. Indirect immunofluorescence studies were done using human cells transfected with a recombinant DNA-harboring cDNA sequence spanning BZLF1 (BamHI Z left frame 1) that was inserted downstream of the adenovirus major late promoter. IgG anti-ZEBRA antibodies were detected in a high proportion of asymptomatic HIV carriers and in AIDS patients but were absent in healthy control individuals. The presence of anti-ZEBRA antibodies in the sera of HIV-positive patients favors the hypothesis that EBV reactivates in such subjects. This finding may be of practical importance in the prognostication of AIDS development.

Adult

Platelet antibodies in serum of patients with human immunodeficiency virus (HIV) infection.

Between 10 and 15% of human immunodeficiency virus (HIV) seropositive individuals develop an immune thrombocytopenic purpura; however, the mechanism involved in platelet destruction is not yet established. In the present work, we have analyzed 208 sera from HIV seropositive individuals, including 85 thrombocytopenic patients, for the presence of autoantibodies against platelet proteins by using the Western blot technique. Our results indicate that: (1) antibodies against platelet proteins were found in 8 of 123 (6.5%) nonthrombocytopenic patients, as compared with 17 of 85 (20%) of thrombocytopenic patients (p less than 0.03); (2) these antibodies appeared to be more frequently found in advanced stages of disease (p less than 0.02); (3) the reactivity of positive sera with antigenic determinants implicated several distinct platelet proteins; (4) antigens thus recognized are unrelated to the major membrane glycoproteins IIb and IIIa, as well as absent in vero cells and trypsin-sensitive cells. Such results underscore the difficulties in establishing the mechanisms involved in platelet destruction during HIV infection.

Autoantibodies

[Anti-tetanus immunization. Complexity and polymorphism of humoral and cellular manifestations].

In general, anti-tetanus vaccination is well tolerated by the recipients, but the repeated inoculations of the vaccine might result in immediate or delayed type of hypersensitivity. The more recent knowledge of the epitopic construction of the toxin defined by tools offered by molecular biology, has helped understand the complexity of humoral and cellular responses as a consequence to vaccination. We have analyzed in this work major antitetanus post-vaccinal manifestations in normal subjects, as well as in patients suffering from different pathological disorders, with regard to immunoglobulin class expression, idiotypic profile, HLA-susceptibility and in vitro cellular responses.

Humans

Detection of anti-mitochondrial antibodies by ELISA and Western-blot techniques and identification by one and two-dimensional gel electrophoresis of M2 target antigens.

Seven hundred and eleven sera were simultaneously studied by immunofluorescence (IF), complement fixation test (CFT) and ELISA for the detection of anti-mitochondrial antibodies (AMA). One hundred and nineteen of these sera were also studied by Western-blot techniques, while some of them were examined by two-dimensional gel electrophoresis so as to identify the polypeptides recognized by M2 antibodies. The results indicated that: (1) ELISA is a more sensitive technique for detecting type M2 AMA (27 scored positive in 27 primary biliary cirrhosis (PBC), as compared to 21/27 by IF and 16/27 by CFT). (2) Although ELISA appeared to be a promising screening method, some false positive results were observed that necessitated a double confirmation of positive sera by another technique. (3) Western-blot experiments with rat mitochondrial purified preparation indicated that sera from AMA type 2 could recognize eight different polypeptides and that most of them identified 63-60, 48, 44, and 35-33 kD polypeptides, whereas the 54 and 27 kD were less frequently recognized. A trypsin treatment of antigens confirmed the enzyme sensitivity of most of these antigens. These results suggested some heterogeneity among M2 AMA, though this series of PBC was not large enough to relate the heterogeneous pattern noticed in Western-blot to the clinical and histological patterns observed in PBC.

Autoantibodies

Idiotypy of anti-Rh antibodies.

Anti-id sera to Rh antibodies were produced by injecting rabbits with purified Rh antibodies. These sera were shown to agglutinate O Rh+ RBC coated by the immunizing antibody and--in some cases--by other anti-D antibodies. Id and cross-reactive id were shown to be located in the antigen-binding and in the non-antigen binding regions of Rh antibodies. An unique example of evolution of idiotypic specificities on human antibodies has been reported. Lastly, we have demonstrated by rosette assay, presence on some PBL of receptors for Fab'2 anti-Rh coating O Rh+ red cells. Rosettes could not be obtained with lymphocytes of a donor and Fab'2 anti-Rh of another individual. Rosettes appeared at a period of time in which the amount of antibody was decreasing.

Agglutination

Idiotypic and anti-idiotypic determinants on lymphocytes during anti-Rh immunization.

Evolution of idiotypic determinants on lymphocytes membrane and presence of other lymphocytes carrying anti-idiotypic determinants, were studied in Rh negative human volunteer blood donors during immunization towards Rh factor. For this purpose E-Rh Rosettes, direct immunofluorescence, inhibition of E-Rh Rosettes by anti-idiotypic sera as well as EA-Rh Rosettes--induced with Fab'2 fragments from anti-Rh antibodies and lymphocytes from the same subject--were examined and compared to the evolution of circulating antibodies. E-Rh Rosettes preceded or accompanied production of anti-Rh antibodies; their frequency decreased after the fifth month following immunization, meanwhile EA-Rh Rosettes increased in parallel with antibody decrease. The direct immunofluorescence and the inhibition of E-Rh Rosettes, by anti-idiotypic sera, show the presence of idiotypic determinants on lymphocyte membranes; the presence of EA-Rh Rosettes, coinciding with the decrease in antibodies demonstrate the existence of lymphocytes bearing auto-anti-idiotypic determinants.

Antibodies, Anti-Idiotypic

[Evolution of anti-Rh antibodies idiotypy in a blood donor over 9 years].

Anti-idiotypic sera were obtained in Rabbits immunized with Rh antibodies (isolated from the serum sample collected in 1974 from a Blood Donor). The sera agglutinate, at high titers, red cells coated with the immunizing antibodies and, at different titers, cells coated with antibodies from serum samples taken at other periods. Inhibition of hemagglutination of anti-idiotypic sera by different samples from the same Donor was complete with the immunizing serum and partial with other samples. These results show that idiotypes or idiotypic specificities appeared or disappeared during the period studied and represent the first observation on evolution of antibody idiotypy in Man.

Animals

Titration of antibodies to tetanus toxoid by agglutination of purified tetanus toxoid sensitized latex particles.

The method of sensitized latex particle agglutination which we have devised allows the selection of samples of plasma for the preparation of immunoglobulins. The population of thus selected samples is the same as is selected by the in vivo test, having a titer greater than or equeal to 6 IU/ml. The test gives a clear-cut difference between the positive and negative results and does not give any prozone phenomenon. It can be used extensively, as the batches of sensitized latex particles may be stored for quite a long time.

Adult