Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2R in vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a "sandwich" enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4+) cells and OKT4-negative (OKT4-) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL-2R were released by PBMC, unseparated T cells, OKT4+ T cells, and OKT4- T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated with Staphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2R in vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4+ and OKT4- T-cell subsets.
We report our experience concerning clinical and paraclinical features of multiple sclerosis in 19 children. The disease was highly variable in its presentation but acute episodes of retrobulbar optic neuritis or transverse myelitis or cerebellitis were commonly observed at the onset. Diagnosis was very often suspected as soon as the first episode when there was clinical evidence of more than one lesion (43%) or study of the cerebrospinal fluid demonstrated a local secretion of immunoglobulins (60%). Evoked potential studies and nuclear magnetic resonance imaging were performed during the course of the disease and exhibited abnormalities of the kind observed in adult patients and with a similar frequency; this suggests that such studies can be very useful in the evaluation of children suspected of having multiple sclerosis. When the initial form of the disease was a chronic myelopathy, the course was progressive from the onset, leading rapidly to a marked invalidity (15%). Most often a succession of relapses and remissions occurred after the first attack and major sequelae appeared 5 to 10 years later. Such features are not very different from those observed in adult patients and suggest that these patients can benefit from the progress resulting from therapeutic trials in adult patients.
With the use of an enzyme-linked immunoabsorbent assay to measure soluble human interleukin 2 receptors (IL 2R), certain human T cell leukemia virus I (HTLV I)-positive T cell lines were found to spontaneously release large quantities of IL 2R into culture supernatants. This was not found with HTLV I-negative and IL 2 independent T cell lines, and only one of seven B cell-derived lines examined produced small amounts of IL 2R. In addition to this constitutive production of soluble IL 2R by certain cell lines, normal human peripheral blood mononuclear cells (PBMC) could be induced to release soluble IL 2R by plant lectins, the murine monoclonal antibody OKT3, tetanus toxoid, and allogeneic cells. Such activated cells also expressed cellular IL 2R measurable in detergent solubilized cell extracts. The generation of cellular and supernatant IL 2R was: dependent on cellular activation, rapid, radioresistant (3000 rad), and inhibited by cycloheximide treatment. NaDodSO4-polyacrylamide gel electrophoresis analysis of soluble IL 2R released from either the HTLV I-positive T cell line HUT 102B2 or normal phytohemagglutinin-activated PBMC demonstrated molecules of apparent Mr = 35,000 to 40,000, and 45,000 to 50,000, respectively, somewhat smaller than the mature surface receptor on these cells. The release of soluble IL 2R appears to be a characteristic marker of T lymphocyte activation and might serve an immunoregulatory function during both normal and abnormal cell growth and differentiation.
Intrathecal synthesis of interferon γ was shown in 14 out of 16 samples of cerebrospinal fluid collected in the first days of disease in adults, children, and newborn infants with herpes encephalitis. This synthesis was concomitant with that of interferon α and was switched off when the specific antibodies in the central nervous system increased. No endogenous interferon γ was detected in 11 serum samples or 13 samples of cerebrospinal fluid collected early in the course of the disease from patients with measles encephalitis and rubella encephalitis, or in serum and cerebrospinal fluid samples from seven patients with subacute sclerosing panencephalitis. In serum collected after the 10th day after the onset of neurological symptoms interferon γ was present at low concentrations in only three out of 11 serum specimens from patients with measles encephalitis or rubella encephalitis.
Interferon γ was present in patients with acute herpes encephalitis and there was active virus replication, but it was not present in postinfectious encephalitis. Possibly the local production of specific antibodies masks the viral antigens and switches off the induction of interferons.
Forced expiratory flow (FEF) at low lung volumes are supposed to be better at detecting lung-function impairment in asthmatic children than a forced volume. The aim of this study was to examine whether FEF results could modify the interpretation of baseline and post-bronchodilator spirometry in asthmatic schoolchildren in whom forced expiratory volumes are within the normal range.Spirometry, with post-bronchodilator vital capacity within 10% of that of baseline in healthy and asthmatic children, was recorded prospectively. We defined abnormal baseline values expressed as z-scores <-1.645, forced expiratory volume in 1 s (FEV1) reversibility as a baseline increase >12%, FEF reversibility as an increase larger than the 2.5th percentile of post-bronchodilator changes in healthy children.Among 66 healthy and 50 asthmatic schoolchildren, only two (1.7%) children with normal vital capacity and no airways obstruction had abnormal baseline forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%). After bronchodilation, among the 45 asthmatic children without FEV1 reversibility, 5 (11.1%) had an FEF25-75% increase that exceeded the reference interval.Isolated abnormal baseline values or significant post-bronchodilator changes in FEF are rare situations in asthmatic schoolchildren with good spirometry quality. @ERSpublications Forced expiratory flows don't add useful information over forced expiratory volumes and their ratio in schoolchildren
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