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Biomedical subjects

D Israel-Biet

Publications and source records attributed to D Israel-Biet.

At least 37 records · Page 2Linked to original sources

Serum suppressive activity of HIV seropositive patients.

The mechanisms by which HIV induces immunosuppression are still poorly understood so far. Several pathways of CD4 cell destruction are known, including cytolysis with or without syncitium formation and killing by cytotoxic effectors of HIV infected or non-infected CD4 cells. However, a discrepancy exists between the small number of actually infected cells in vivo and the extent of HIV-related immunodeficiency. Among other possible immunosuppressive factors, serum blocking factors have been reported, but only in AIDS-related opportunistic infections (OI), i.e. in a quite specific type of full-blown HIV disease. The purpose of this work was to determine whether serum blocking activity was unique to this group of patients, or if it was also expressed in other clinical presentations and, moreover, at earlier stages of the disease. We also attempted to delineate the nature of these seric factors. In order to do so, we assessed serum suppressive activity of 50 HIV seropositive patients, seven with OI, eight with Kaposi's sarcoma (KS), and 35 with no clinical AIDS. Our results confirm the existence of serum inhibiting factors in AIDS, and demonstrate their presence at earlier stages of the disease. They also highlight the fact that the level of serum suppression does not correlate with patients clinical status, but increases with the severity of the disease. The lower the CD4 count, the higher the suppression exerted. Furthermore, we showed that the suppression was at least partly mediated by small size molecules, which are not complement-mediated or directly lymphocytotoxic. On the other hand, this activity does not correlate with the serum level of p24 HIV core protein. The possible relation with other viral components is discussed. The relevance of these data to prognosis and pathogenesis of HIV disease deserves further investigation.

Acquired Immunodeficiency Syndrome↗

[Broncho-alveolar lavage in pulmonary involvement in rheumatoid arthritis].

This study was designed to investigate by bronchoalveolar lavage (BAL) the characteristics of lung involvement in rheumatoid arthritis (RA). Twenty six patients with RA were included; ten were active smokers. Chest X Ray, pulmonary function tests and BAL were performed in all patients. Bronchiolitis was found in 7% of cases, pleurisy in 30% of cases. 83% of patients were found to have diffuse alveolar and/or interstitial disease, 17% rheumatoid nodules. Functional evaluation showed a restrictive pattern and a significant reduction in the carbon monoxyde diffusing capacity. Smokers had elevated BAL macrophages and decreased lymphocytes compared with non-smokers: respectively 89% vs 62.9% and 7.3% vs 18.9%. Patients with bronchiolitis had lower FVC than others: 38 +/- 14% vs 61 +/- 3%, and their BAL neutrophils were increased: 71 +/- 23% vs 7.5 +/- 2%. There was an inverse correlation between neutrophil counts and FVC in non-smokers, and diffusing capacity. We conclude that BAL inflammatory cells profiles are abnormal in RA and modified by a smoking history and the existence of a bronchiolitis.

Arthritis, Rheumatoid↗

Serum HIV antigen and anti-P24-antibodies in 200 HIV seropositive patients: correlation with CD4 and CD8 lymphocyte subsets.

Serum HIV (P24) antigen (Ag) measured by an antigen capture ELISA (Abbott) and anti-P24-antibodies (Abs) measured by a competitive ELISA (Abbott) and by Western Blot (Dupont de Nemours) analysis were correlated with lymphocyte subsets (CD4 and CD8) in 174 HIV seropositive patients without AIDS (non-AIDS) and 26 with AIDS. In the non-AIDS group, 27% of the patients were anti-P24-Ab negative and 21% were Ag positive while in the AIDS group these figures were 62% and 54% respectively (P less than 0.001). Overall, a significant correlation exists between the Ab-Ag profile and the CD4 cell count: the percentage of patients with anti-P24-Ab positive and Ag negative decreases from 90% for patients with more than 900 CD4 cells/microliter to 21% for patients with 100 and less CD4 cells/microliter; on the contrary, the percentage of patients with anti-P24-Ab negative and Ag positive increases from 0% over 800 CD4 cells to 53% under 100 CD4 cells/microliter. A weak correlation may also exist with the CD8 cell count. The subgroup of patients with 1,000 or more CD8 cells/microliter have a higher (but not significant) percentage of subjects with Ag positive and anti-P24-Ab negative than the subgroup with less than 1,000 CD8 cells/microliter. A short-term longitudinal study (mean follow-up: 1 year) was performed on 80 non-AIDS subjects: 77% (10/13) of those who had a CD4 cell decrease (greater than 30%) were initially Ag positive, while only 21% (14/67) of those without a decrease were Ag positive at the beginning (P less than 0.1). Although the relative weight and individual predictive value of each of these parameters need to be classified, they are probably the best biological markers currently available for monitoring clinical trials with experimental drugs.

Acquired Immunodeficiency Syndrome↗

Pulmonary complications of intravesical Bacille Calmette-Guérin immunotherapy.

Lungs have rarely been reported to be affected by any side effects of BCG therapy. Interstitial pneumonitis, though, is known to occur under such circumstances, but its pathogenesis is still debated between an infectious and a hypersensitivity mechanism. We report here 3 cases of pulmonary complications of BCG therapy evaluated by bronchoalveolar lavage (BAL). Cellular data obtained from all 3 patients were characterized by a markedly increased alveolar lymphocytosis. The T4/T8 ratio was elevated compared with that in normal subjects and with the T4/T8 ratio of circulating lymphocytes. Furthermore, alveolar lymphocytes were highly sensitized to PPD, as evaluated by their proliferation and their production of interleukin 2 in the presence of PPD. Mycobacteria were not found in the 3 patients. We conclude that interstitial pneumonitis occurring during BCG therapy could be explained by a hypersensitivity phenomenon, leading to an intense immune and lymphocyte-mediated response within involved organs.

Adult↗

Persistent high alveolar lymphocytosis as a predictive criterion of chronic pulmonary sarcoidosis.

A homogeneous population of 73 sarcoidosis patients with recent onset sarcoidosis, no smoking habits, and no previous treatments was serially evaluated in a study of the spontaneous evolution of sarcoidosis. This evaluation comprised clinical, radiographic, biological, and functional assessments as well as assessments of fluids recovered by BAL. We determined the natural history of alveolar lymphocytosis in early stage sarcoidosis and the predictive value of such lymphocytosis for the outcome of the disease. We focused on the outcome at 2 years because it is the usual time of spontaneous recovery; after 2 years the disease enters the chronic phase, and more complications are likely to occur. We found that the initial lymphocytosis observed during the very early stages of the disease had no predictive value for the outcome. Conversely, the persistence of a high alveolar lymphocytosis within the first year of evolution is strongly correlated to a nonrecovery at 2 years, and thus to a chronic phase of sarcoidosis.

Adult↗

Human alveolar macrophage subpopulations isolated on discontinuous albumin gradients. Cytological data in normals and sarcoid patients.

Cells recovered by bronchoalveolar lavage (BAL) from ten subjects (five normals and five sarcoid patients) were centrifuged on discontinuous albumin gradients to study alveolar macrophage (AM) heterogeneity. The gradient was made with nine bovine albumin concentrations (from 8 to 30%). After centrifugation (4000 X g) cells were recovered from the interfaces. The majority of AM was recovered in upper and medium layers with AM purity reaching 90-100% in upper layers, while lymphocytes and granulocytes were found in lower layers. Alveolar macrophage morphology was different along the gradient. Large cytoplasmic vacuoles were found in AM from upper layers. Alveolar macrophage cytoplasmic diameters decreased from the top to the bottom of the gradient, but AM from sarcoid patients appeared larger than AM from normals. Alveolar macrophage nucleo-cytoplasmic ratios increased from top to bottom, but were lower in sarcoid patients than in normals. Alveolar macrophage peroxidase activity was rare (0.5-2% of AM) but reached a higher proportion in upper and lower layers.

Adult↗

Human alveolar macrophage subpopulations isolated on discontinuous albumin gradients: functional data in normals and sarcoid patients.

Cells recovered by bronchoalveolar lavage from seven normals and seven sarcoid patients were centrifuged on discontinuous bovine albumin (BSA) gradients to study alveolar macrophage (AM) heterogeneity. The gradient was made with nine BSA concentrations from 8 to 30%. After centrifugation, the cells were recovered from the nine interfaces, named a to i. The majority of the AM was recovered from layers b to g. Regulatory activity of AM subpopulations was tested on mitogen-induced blood mononuclear cells (BMC) proliferation: autologous BMC were cocultured with AM from the different layers; 16-h culture supernatants of AM subfractions were added to allogeneic BMC cultures from normal donors. In the autologous assay, AM from the middle layers exhibited a stimulatory activity in normals and even more in sarcoid patients, while AM from the upper layers showed an inhibitory activity in normals but a stimulatory activity in sarcoid patients. In the allogeneic assay, a suppressive effect was found in culture supernatants from normal AM. On the other hand, in sarcoid patients, culture supernatants were less inhibiting, but the inhibitory activity was in both cases maximal in b. These results confirm functional heterogeneity of human AM, and demonstrate that the AM subpopulations differ between normals and sarcoid patients.

Adult↗