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Biomedical subjects

A Larsen

Publications and source records attributed to A Larsen.

At least 91 records · Page 5Linked to original sources
PubMed1988

Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes.

To determine whether the production and secretion of TNF and IL-1 by human mononuclear phagocytes could be independently modulated, we examined secretion of TNF and IL-1 by fresh monocytes and monocytes pretreated with IFN-gamma or granulocyte macrophage CSF before LPS stimulation. TNF and IL-1 secretion were in part differentially modulated. Fresh monocytes secreted large amounts of TNF and IL-1 after LPS stimulation and less than 6% as much without LPS. The capacity to secrete TNF in response to LPS decreased slightly in cultured monocytes but was markedly augmented by IFN-gamma (approximately five-fold more than fresh monocytes). In contrast, cultured monocytes secreted less than 5% as much IL-1 as fresh monocytes and, although augmented by IFN-gamma, IL-1 secretion remained much less than by fresh monocytes. These differences in modulation were reflected by differences in the molecular mechanisms regulating TNF and IL-1 secretion. TNF secretion was regulated primarily by changes in the duration of increased transcription and by an apparent increase in translation or protein stability in response to LPS; greater than 95% TNF produced was secreted under all conditions. In contrast, the changes in IL-1 secretion reflected primarily post-transcriptional regulation of IL1-alpha mRNA, transcriptional and post-transcriptional regulation of IL-1 beta mRNA and a decrease in the fraction of IL-1 secreted by cultured compared with fresh monocytes (10 and 60%, respectively). Changes in translational efficiency or protein processing or stability appeared not to be important mechanisms regulating IL-1 secretion. Additional evidence that TNF and IL-1 can be differentially modulated was the selective decrease in TNF secretion and the failure of IFN-gamma to enhance TNF secretion by cultured monocytes from neonates, whereas results for IL-1 were similar with adult and neonatal monocytes. Results with tissue macrophages were similar to those with cultured monocytes. These results indicate that TNF and IL-1 production and secretion by mononuclear phagocytes can be differentially modulated, reflecting in part different mechanisms of regulation; this may allow them to play partially independent roles in the host immune response.

Adult↗
PubMed1988

Restricted production of interleukin 4 by activated human T cells.

Interleukin 4 (IL-4) is secreted by activated T cells and pleiotropically modulates both B- and T-lymphocyte function. In murine helper (CD4+) T-cell clones IL-4 production appears to be regulated independently of interferon gamma and interleukin 2. To determine whether production of these lymphokines is also differentially regulated in uncloned human T cells, we studied lymphokine production by normal human peripheral T cells and T-cell subsets after in vitro polyclonal activation. After maximal induction of lymphokine expression, IL-4 mRNA was detectable in less than 5% of CD4+ and 1-2% of unfractionated T cells, whereas approximately 33% and 60% of CD4+ cells expressed detectable mRNA for interferon gamma and interleukin 2, respectively. This finding correlated with dramatically lower production of IL-4 mRNA and protein than of interferon gamma and interleukin 2 by peripheral blood and tonsillar T cells. The helper-inducer (CD4+ CD45R-) T-cell subset, which significantly enhances in vitro immunoglobulin production, accounted for the preponderance of IL-4 mRNA accumulation and protein production by CD4+ T cells; nevertheless, cells with detectable IL-4 mRNA constituted less than 10% of the CD4+ CD45R- subset. Limitation of IL-4 production to a comparatively small population of normal human T cells could selectively regulate the effects of this lymphokine in T-cell-mediated immune responses; such selective regulation may be a fundamental mechanism for restricting the potentially pleiotropic effects of certain lymphokines to appropriate responder cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Competence and stress in school children: the moderating effects of individual and family qualities.

This study examined the associations of stress exposure to various aspects of school-based competence in a normative sample of 205 children aged 8-13. Potential moderators of these relations, including child attributes of sex and IQ and environmental attributes of socioeconomic status (SES) and family qualities, were also studied. Stress exposure was indexed by a life event questionnaire. Competence was assessed by teacher ratings, peer assessments and school record data. Family attributes were derived from a set of rating scales completed by interviewers after 6 hours of interviews with a parent. Results suggest that the relations of stress exposure to competence vary as a function of individual differences as well as the competence criterion. Disadvantaged children, with lower IQ and SES, and less positive family qualities, were generally less competent and more likely to be disruptive at high stress levels. Advantaged children were more competent, and with stress positively engaged in school, but were not likely to be disruptive. Boys were less socially competent than girls and, when stress was high, appeared to be less protected by positive family qualities. Causal hypotheses for future research in this area are discussed.

Achievement↗
PubMed1988

Cell cycle-dependent interleukin 1 gene expression by cultured glomerular mesangial cells.

Glomerular mesangial cell (MC)--derived IL-1 may be an important factor in the development of the hypercellularity and sclerosis characteristic of many forms of glomerulonephritis. To define the regulation of IL-1 synthesis by human MC, Northern blot analyses were performed using specific probes for monocytic IL-1 alpha and beta mRNA. Proliferating MC expressed mRNA for both IL-1 alpha and beta, whereas nonproliferating MC contained no detectable IL-1 mRNA. Synchronized MC expressed IL-1 alpha and beta mRNA within 2 h of stimulation with serum. This serum effect could be reproduced with platelet-derived growth factor and epidermal growth factor. Immune precipitations of 35S-methionine-labeled cells indicate that the mesangial IL-1 is synthesized as a 33-kD precursor protein with a pI of 7.2. Extracellular mesangial IL-1 has a pI of 7.0 and molecular weight of 17 kD, consistent with its identification as IL-1 beta. Cellular proliferation in glomerular disease may be driven in part by peptide growth factor-mediated induction of mesangial IL-1 gene expression and protein synthesis.

Cell Cycle↗
PubMed1988

The relation of radiographic changes to serum acute-phase proteins and rheumatoid factor in 200 patients with rheumatoid arthritis.

Radiographic parameters in 200 patients with rheumatoid arthritis (RA) were correlated with laboratory parameters, including hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), orosomucoid (OROS), immunoglobulin G (IgG), IgM, IgA, and rheumatoid factor (RF). CRP, OROS, and Hb showed a significant association with the severity and progress of radiographic parameters. ESR and WARO showed a significant association with the severity of radiographic parameters in late RA only. IgG, IgM, and IgA did not show any significant correlation with radiographic parameters.

Adult↗
PubMed1987

IL 1 expression in a clone of human T cells.

Three human T cell clones, all of which are T3+, T4+, T8-, and T11+, were examined for IL 1 production. Two clones were found to express readily detectable, membrane-bound IL 1 activity upon stimulation with OKT3 antibody, rIL 2, and PMA. Northern blot analysis of RNA from one of the clones shows that cells can be induced to express the genes for both IL 1 alpha and IL 1 beta. Furthermore, the pattern of expression in response to different stimuli suggests that the genes for IL 1 alpha and IL 1 beta are regulated independently.

Antibodies, Monoclonal↗
PubMed1987

The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor.

Both IL-1 alpha and IL-1 beta are initially translated as approximately Mr 30,000 polypeptides and processed to approximately Mr 17,500 prior to, or during, release from macrophages. The current study utilizes an in vitro transcription-translation system to produce these four forms of IL-1 directly from cloned cDNAs, in order to investigate the relative receptor binding and biological activities of the proteins. The data show that the initial translation product from IL-1 beta mRNA must be processed in order to bind to the IL-1 receptor and hence express biological activity. By contrast, the initial translation product of IL-1 alpha mRNA can bind to the IL-1 receptor without further proteolytic processing. These data suggest that the IL-1 biological activity previously associated with proteins having Mr values in the range 30,000-40,000 is due to IL-1 alpha gene products.

Binding, Competitive↗
PubMed1987

Production of IL-1 alpha and IL-1 beta by clones of EBV transformed, human B cells.

An EBV transformed B-cell line was derived from peripheral blood cells from a single donor. B-cell clones were isolated from that line and analyzed for transcription of IL-1 genes, production of biologically detectable IL-1 and antigen presenting capabilities. One clone was found to secrete IL-1 activity into tissue culture medium, and to express the gene for IL-1 alpha. Three other clones were positive for cell surface IL-1 activity but no activity could be detected in culture supernatants. Those clones express the gene for IL-1 beta but not IL-1 alpha. All clones were approximately equal in their ability to present antigen to resting and primed T cells.

Antigen-Presenting Cells↗
PubMed1987

Evaluation of central nervous system involvement in uncomplicated optic neuritis after prolonged follow-up.

Magnetic resonance imaging (MRI), multimodal evoked responses (ER) and HLA antigens were examined in 10 patients with idiopathic acute optic neuritis (ON) without any clinical symptoms or signs of multiple sclerosis (MS) during 9-14 years. In MRI, abnormalities compatible with MS were seen in 4 patients. In spite of clinically unilateral ON, a bilateral abnormality in visual evoked responses (VER) was seen in 3 of 9 cases. Brain stem auditory evoked responses (BAER) were normal in all cases, short latency somatosensory evoked response (SER) in all but one. The cerebrospinal fluid at time of ON showed signs of demyelination in one case only. The frequency of HLA antigens DR2 (78%) and B18 (40%) was significantly increased in comparison to healthy controls. MRI seems to be the most sensitive method in the detection of cerebral lesions of MS, especially in mild or asymptomatic forms of the disease. The present techniques are, however, mostly unable to demonstrate optic nerve lesions which more reliably can be evaluated by VERs. The question whether idiopathic ON represents a form of MS solely, cannot be resolved.

Adult↗
PubMed1987

Hand radiography of 200 patients with rheumatoid arthritis repeated after an interval of one year.

Hand radiography of 200 patients with rheumatoid arthritis RA was repeated after an interval of 12 months. Twenty joints including ten metacarpophalangeal joints, eight proximal interphalangeal joints and two interphalangeal joints of the thumbs were assessed. The number of joints with erosion was recorded, being referred to as Erosion Score. Additionally, each joint was graded on a zero to five point scale and the gradings of the individual joints were summed to form a score referred to as Damage Score. The progression in these scores during 12 months was recorded. The radiological joint damage was found to develop rapidly during the first years after disease onset and to assume a slow rate of increase after 9 years of the disease. The results imply that the disease duration is a critical feature for therapeutic studies. We suggest that patients with disease duration of less than 36 months only are suitable for therapeutic trials of RA and that the follow-up time should be at least 18 months if radiological assessment is used.

Arthritis, Rheumatoid↗
PubMed1987

Expression of HLA class II antigens and secretion of interleukin-1 by monocytes and macrophages from adults and neonates.

HLA class II antigen expression and IL-1 production by mononuclear phagocytes are important for antigen-stimulated T-cell activation. We examined these surface antigens and a monocyte marker antigen on fresh cord and adult blood monocytes, macrophages (M phi) derived from monocytes in vitro, human placental (fetal) M phi, from adult women. By FACS analysis, we found less DR on cord blood monocytes (80 +/- 7) than on adult monocytes (96 +/- 1) with greater heterogeneity in density of DR due to a weakly staining subpopulation of cord monocytes. There were markedly fewer DR and DQ positive placental M phi, 62 +/- 11% and 19 +/- 3%, compared to adult peritoneal M phi, 91 +/- 11% and 87 +/- 13%. DQ was more intense on peritoneal M phi than on any other cell type. Fresh cord monocytes secreted equal or greater amounts of interleukin-1 (IL-1) in response to lipopolysaccharide (LPS) or Group B streptococci than adult monocytes, although results with individual preparations varied. By Northern blot analysis, LPS-stimulated cord blood and adult monocytes contained similar amounts of IL-1 alpha, IL-1 beta and DR alpha mRNA. Each placental M phi preparation secreted IL-1 (200 +/- 85 U/ml to LPS). Peritoneal M phi preparations from women in the pre-luteal phase did not release detectable IL-1, whereas those from women in the post-luteal phase released as much as monocytes. Cultured monocytes failed to secrete IL-1 and expressed less DQ than fresh monocytes. Exposure to IFN gamma augmented IL-1 release by adult and cord cells and DQ expression on cord cells. These data indicate that class II antigen expression and IL-1 secretion by mononuclear phagocytes are only in part co-ordinately modulated. The differences between placental (fetal) M phi and adult peritoneal M phi may reflect both tissue-specific differences and generally diminished class II antigen expression on fetal and neonatal mononuclear phagocytes.

Adult↗
PubMed1986

Expression of interleukin 2, interferon-gamma, and the IL 2 receptor by human peripheral blood lymphocytes.

Human peripheral blood T lymphocytes were treated with recombinant interleukin 2, mitogens, and dexamethasone. The resulting accumulation of mRNA for interleukin 2 (IL 2), the interleukin 2 receptor (IL 2R), and interferon-gamma (IFN-gamma) was measured. IL 2 was found to regulate the levels of each of these mRNA. The expression of mRNA for IL 2, IL 2R, and IFN-gamma correlated very well with the levels of protein observed. In populations of peripheral blood T lymphocytes, the production of IL 2 and IFN-gamma were not necessarily coordinately expressed. The sequential expression of these mRNA was investigated in order to determine whether they might be independent of the action of IL 2. IFN-gamma and IL 2 mRNA showed biphasic accumulations. IL 2 mRNA accumulated very rapidly, within 60 min after mitogen stimulation and before any detectable IL 2R mRNA accumulation. Similarly, IFN-gamma mRNA accumulated rapidly, simultaneously with IL 2 mRNA. This early peak of IFN-gamma mRNA, therefore, is likely to be independent of IL 2 action. Both IL 2 and IFN-gamma mRNA then showed later peak times of accumulation. IL 2 mRNA levels peaked at 5 hr after mitogen stimulation, whereas IFN-gamma mRNA levels peaked at 20 hr. IL 2R mRNA continued to accumulate for the full 40 hr of these kinetic experiments. The later accumulations of IFN-gamma and IL 2R mRNA and the resulting expression of the corresponding proteins may therefore be dependent on the earlier production of IL 2 and its subsequent interaction with the IL 2R on the surface of such activated T cells.

Dexamethasone↗