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M Hurme

Publications and source records attributed to M Hurme.

At least 145 records · Page 8Linked to original sources
PubMed1990

Time-resolved immunofluorometric assays for trypsinogen-1 and 2 in serum reveal preferential elevation of trypsinogen-2 in pancreatitis.

We have developed sensitive time-resolved immunofluorometric assays for the two trypsinogen isoenzymes, trypsinogen-1 and trypsinogen-2, which also are called cationic and anionic trypsinogen, respectively. The assays use monoclonal antibodies produced by immunization with tumor-associated trypsinogen that is isolated from mucinous ovarian cyst fluid. In each assay, one antibody is immobilized onto the walls of polystyrene microtiter strip wells and the other is labeled with an europium(III) chelate. The cross-reaction of each trypsinogen isoenzyme in the assay for the other isoenzyme is less than 1%. The detection limits are 0.1 micrograms/L for trypsinogen-1 and 0.3 micrograms/L for trypsinogen-2. In sera of healthy subjects and patients with extrapancreatic disease the concentration of trypsinogen-1 is higher (median, 21 micrograms/L) than that of trypsinogen-2 (median, 17 micrograms/L), but in acute pancreatitis the ratio is reversed. In acute pancreatitis the concentration of trypsinogen-2 is 50-fold higher than in controls, whereas the difference in trypsinogen-1 concentrations is only 15-fold. The corresponding difference in immunoreactive trypsin measured by a commercially available radioimmunoassay was also only 10-fold.

Acute Disease↗
PubMed1989

Mechanism of T cell proliferation in vivo: analysis of IL-2 receptor expression and activation of c-myc and c-myb oncogenes during lymphatic regeneration.

The mechanism of T cell proliferation was studied using in vivo lymphatic regeneration as the model. Lymphatic regeneration was induced by injecting a sublethal dose (300 mg/kg) of cyclophosphamide (Cy) into mice. Majority of the regenerating splenic T cells were found to be in the cell cycle, nearly 30% being found in S/G2+M phases resembling the ratio obtained for mitogen activated T cells in vitro. Expression of interleukin-2 receptor (IL-2R) was defined by the monoclonal anti-IL-2R antibody, AMT-13. Only 1-3% of regenerating T cells were IL-2R positive (while about 30% of the in vitro activated T cells were IL-2R positive). Accordingly, these cells did not respond to IL-2 in vitro. However, when the freshly isolated regenerating T cells were cultured in the presence of Con A or PMA + ionophore A 23187, IL-2R was readily induced. The regenerating T cells were further analyzed for the expression of the cellular oncogenes c-myc and c-myb. These cells expressed about three times more c-myb mRNA than Con A-stimulated T cells and the levels were comparable to those seen in thymocytes. By contrast, the amount of c-myc mRNA was similar in the regenerating T cells and in Con A-activated T cells, but weak or barely detectable in splenocytes and thymocytes. Taken together, our results imply that the vigorous T cell proliferation during cyclophosphamide-induced lymphatic regeneration is independent of the IL-2/IL-2R hormone system, like T-cell precursor proliferation in the thymus, and is characterized by both high c-myb expression typical for thymocytes and high c-myc expression typical for in vitro proliferation-activated T cells.

Animals↗
PubMed1989

Transforming growth factor-beta does not alter interleukin-1 expression in cultured human macrophages.

Transforming growth factor-beta (TGF beta) is a growth modulator that stimulates the growth of fibroblastic cells but inhibits the growth of cells of epithelial origin. TGF beta also influences the production of extracellular matrix proteins, and of proteases and the type 1 plasminogen activator inhibitor (PAI-1) by cultured cells. TGF beta appears also to have various immunoregulatory effects, suppressing both T- and B-cell activities. It has been proposed that it might increase the expression of interleukin-1 (IL-1) mRNA in cultured human monocytes, thus potentiating immune functions. To analyze the role of TGF beta in IL-1 production we have now quantitated the effect of this factor on the production of biologically active IL-1 as well as IL-1 beta mRNA expression. The effect of TGF beta on IL-1 production optimally activated with bacterial lipopolysaccharide (LPS) was also studied. It was found that IL-1 activity and mRNA levels were rapidly elevated by LPS but not by TGF beta. Culture fluids from monocytes treated with TGF beta alone or with TGF beta plus LPS inhibited the proliferation of the test thymocytes. After gel filtration, the media from TGF beta-treated cultures showed no activity in the molecular weight area of IL-1 (approx. 15 kD), while the supernatants from TGF beta plus LPS-induced cells contained IL-1 activity in these fractions, the magnitude of which was, however, at the same level as in the culture fluids derived from cells stimulated with LPS alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1989

Cytokine modulation of HLA-DR expression on proliferating cord blood T cells.

HLA class II antigens are not expressed on resting T cells, but upon activation, their expression is readily induced on most mature T cells. T cells derived from cord blood (CB), however, remain HLA class II even when actively proliferating. To examine the reason for this deficiency, we have now tried to modulate HLA class II expression with three cytokines: interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and interleukin-1 (IL-1); all of which are known to modulate HLA class II expression in various cell types. Although CB T cells are not, in contrast to mature T cells, able to produce IFN-gamma, IFN-gamma did not have any effect on the amount of cell surface HLA-DR antigens. IL-1 was also without effect, but TNF increased the proportion of HLA-DR+ cells in both CB and adult peripheral blood (PBL)-derived T lymphoblasts. Northern blotting analysis of the HLA-DR mRNA levels revealed that in CB cells the levels were 5-6 times lower than in the PBL-derived lymphoblasts, indicating that the lower HLA-DR antigen expression in CB T cells is due to transcriptional regulation. Of the cytokines tested, only TNF had an effect on the steady-state HLA-DR mRNA levels, increasing the levels in both CB and PBL-derived T-blasts 2-3-fold.

Antigens, Surface↗
PubMed1989

Histological and enzyme histochemical study on the injured knee meniscus in human.

The activity and distribution of 10 enzymes was determined in the ruptured knee meniscus of 23 patients, when meniscus was operatively removed. The activities of NADH and SDH indicating oxydative energy metabolism were low in the ruptured meniscus as well as in the synovium close to it. On the contrary, NADPH and LDH, indicating anaerobic energy metabolism and G-6-PDH as an indicator of pentose-phosphate shunt, showed moderate or high activity. The activities of GLDH, ATPase, AcPase, AlPase, and LAPase were low in the meniscus tissue, but moderate and sometimes high in synovial tissue and fibroblasts close to the meniscus. In the vascular walls these enzyme activities all were moderate or high indicating reparative capacity in the peripheral, vascularized part of meniscus. The age of the patients as well as the time interval between the trauma and the operation was not in relationship with enzyme activities studied.

Adult↗
PubMed1989

Connective tissue changes of the multifidus muscle in patients with lumbar disc herniation. An immunohistologic study of collagen types I and III and fibronectin.

The connective tissue components, Types I and III collagen fibronectin, were immunohistologically analyzed using their specific antibodies for localization and semiquantitative estimation in 24 patients (11 women and 13 men, all under 55 years of age) operated on for herniated lumbar intervertebral disc. Nine cadavers without known back problems (2 women, 7 men) served as controls. In controls, Type I collagen was present in the endo- and perimysial structures of the muscle, more conspiciously in the former. Type III collagen, together with fibronectin, were more abundant in the perimysium than in the endomysium. Thickening of these structures was not evident in the controls. In most patients Types I and III collagen and fibronectin distribution was similar to that of the controls. However, fibrotic changes of both and endo- and perimysial structures involved all Types I and III collagen and fibronectin in ten cases. In two patients an increase in Type I collagen staining intensity in the endomysium was recorded and thickening of the endomysial structures was observed in six patients. There were correlations with the severity of the connective tissue structural changes to atrophy of the muscle and furthermore to disability of the patient in the 1-year postoperative check-up. These findings suggest that if marked fibrosis of the muscle occurs, it can be a factor impairing recovery from the disease during the long-term postoperative course.

Adult↗
PubMed1989

Antibody responses to hapten in thymectomized mice: extraordinarily pronounced deficiency in IgG1 production.

The effect of thymectomy on the production of antibodies was studied by immunizing mice with hapten-carrier conjugates. Antibody responses were analysed with monoclonal antibody-based quantitative isotype-resolving assays. In spite of bone marrow reconstitution, irradiation without thymectomy caused a long-lasting relative deficiency in responsiveness to T-independent antigens. Even when no visible remnants of the thymus could be observed at the autopsy of thymectomized mice, there appeared to be a gradual recovery of antibody-forming capacity within 4 months, as assessed by the response to a T-dependent antigen. Therefore, some of the thymectomized mice had to be regarded as having recovered with respect to the helper T-cell effect. The antibody responses to T-dependent antigens were improved in all isotypes by a functional T-cell system, but the IgG isotypes seemed to benefit more than IgM. The most conspicuous deficit in antibody production in non-recovered thymectomized mice was observed in the T-dependent responses of the IgG1 isotype (2000-fold reduction in contrast to about 50- to 100-fold in IgG2a, IgG2b, and IgG3).

Animals↗
PubMed1989

Induction of interleukin 1 alpha (IL-1 alpha) and IL-1 beta mRNA expression and cellular IL-1 production by anti-HLA-DR antibodies in human monocytes.

We studied the role of HLA class II antigens in the regulation of interleukin 1 (IL-1) production in human monocytes. Monocytes were cultured with monoclonal anti-HLA-DR antibodies for 24 h after which cellular (i.e. intracellular and membrane-associated) IL-1 production, IL-1 secretion, and the expression of IL-1 alpha and IL-1 beta mRNA were determined. One of the anti-HLA-DR antibodies tested (anti-HLA-DR, Becton Dickinson) clearly induced IL-1 alpha and IL-1 beta mRNA expression and cellular IL-1 production. The other anti-HLA-DR antibody tested (OKIa1, Ortho) had no effect on IL-1 production. The stimulatory effect of anti-HLA-DR was enhanced by IFN-gamma in both fresh and aged monocytes. A synergistic effect by anti-HLA-DR and suboptimal doses of LPS (1 ng/ml) on both cellular IL-1 production and secretion was also demonstrated. The possibility of contaminating LPS causing the IL-1-inducing effect of anti-HLA-DR was excluded by the inability of polymyxin B to abolish the anti-HLA-DR-induced IL-1 production.

Adjuvants, Immunologic↗
PubMed1989

The effect of gamma interferon on interleukin 1 release of human monocytes. Dependence on the activating agent and correlation to the mRNA levels.

The effect of gamma interferon (IFN-gamma) on interleukin 1 (IL-1) production by human monocytes induced either by bacterial lipopolysaccharide (LPS) or silica dust was examined. Release of biologically active IL-1 from LPS-activated monocytes was enhanced in a dose-dependent manner with IFN-gamma. The augmenting effect of IFN-gamma was most marked in monocytes stimulated with a sub-optimal dose of LPS (1 ng/ml). IFN-gamma delivered the augmenting effect only if present at the beginning of the IL-1 induction. The IL-1 released in the presence of IFN-gamma was characterized by gel filtration on fast protein liquid chromatography (FPLC) and by isoelectric focusing; the augmented form of IL-1 was a 17 kDa molecule, with pI 7, i.e. IL-1 beta. In contrast to these data, IFN-gamma had a decreasing effect on IL-1 release by monocytes stimulated with silica dust; in monocyte cultures stimulated with a sub-optimal dose of silica (100 micrograms/ml), only minute amounts of biologically active IL-1 were released in the presence of IFN-gamma. With higher silica concentrations the decreasing effect was less strong. The effects of IFN-gamma on the levels of IL-1 beta mRNA were also analysed. IFN-gamma did not alter the accumulation of IL-1 beta mRNA in LPS-stimulated monocytes. In contrast, in silica-stimulated monocytes IFN-gamma reduced the steady-state levels of IL-1 beta mRNA. Thus, these data indicate that, depending on the stimulating agent, IFN-gamma either down- or up-regulates IL-1 production; the former takes place mainly at the level of transcription, while the latter occurs with post-transcriptional mechanisms.

Humans↗
PubMed1989

Comparison of interleukin 1 release and interleukin 1 mRNA expression of human monocytes activated by bacterial lipopolysaccharide or synthetic lipid A.

Several of the biological effects of bacterial lipopolysaccharide (LPS) can be induced by the lipid A part of the molecule. Here we show that in human peripheral blood monocytes, synthetic E. coli lipid A is as effective as the whole LPS molecule in inducing the production of interleukin 1 (IL-1) bioactivity which remains associated to the cells (i.e. IL-1 alpha). In contrast, LPS- but not lipid A-stimulated cells released the bioactive IL-1 produced into the culture supernatant (mainly IL-1 beta). Northern blotting analysis demonstrated, however, that LPS and lipid A are equally effective in inducing the accumulation of IL-1 alpha and IL-1 beta mRNA. These data support the hypothesis that induction of IL-1 biosynthesis and activation of the secretory mechanism for IL-1 are independent phenomena.

Cells, Cultured↗
PubMed1989

Patellofemoral relationships in recurrent patellar dislocation.

Magnetic resonance imaging was used to analyse the patellofemoral relationships during the first 30 degrees of knee flexion in women with recurrent patellar dislocation. The patellofemoral joints were imaged both sagittally and axially with the knee flexed 0 degrees, 10 degrees, 20 degrees, and 30 degrees. At the beginning of knee flexion the sulcus angle was greater than in unaffected women, the lateral patellofemoral angle was smaller, the patella displaced further laterally, tilted more laterally and the congruence angle was directed more laterally. At 30 degrees of knee flexion these differences were less marked than at 0 degree to 10 degrees. Logistic regression analysis showed that the sulcus angle at 10 degrees of knee flexion was the most diagnostic feature, indicating that there is an anatomical predisposition to recurrent dislocation and that pathological patellar tracking starts from the beginning of flexion. Traditional sunrise radiographic films taken at 25 degrees to 30 degrees knee flexion clearly miss diagnostically important information.

Adolescent↗
PubMed1988

Interleukin-4 inhibits interleukin-1 synthesis by a posttranscriptional mechanism.

T cell derived cytokines, interleukin-2 and interferon-gamma, are known to upregulate the interleukin-1 synthesis of monocyte/macrophages. The effect of a third T cell derived cytokine, interleukin-4, was now investigated. Human peripheral blood monocytes were activated with bacterial lipopolysaccharide in the presence or absence of interleukin-4 and the production of biologically active interleukin-1 was quantitated both from the culture supernatants and from the monocyte lysates using the mouse thymocyte assay. Interleukin-4 had a clear dose-dependent suppressive effect on the interleukin-1 synthesis. IL-1 alpha and IL-1 beta mRNA levels, quantitated by Northern blot analysis, were equally high in the lipopolysaccharide plus interleukin-4 supplemented cultures and in the cultures with lipopolysaccharide alone, suggesting that the effect of interleukin-4 in the interleukin-1 biosynthesis is post-transcriptional.

Animals↗
PubMed1988

Accessory cells, dendritic cells, or monocytes, are required for the lymphokine-activated killer cell induction from resting T cell but not from natural killer cell precursors.

In this study we have investigated the role of accessory cells in the development of lymphokine-activated killer cells (LAK) from highly purified human NK and small resting T cell progenitors. As accessory cells we used autologous, as well as allogeneic, monocytes, and dendritic cell enriched cells. Both NK and T cells were able to generate LAK activity, but their activation requirements were different. NK cells were activated merely by IL-2, and accessory cells did not enhance their lytic activity in the presence or absence of IL-2. Conversely, T cells were practically unresponsive to even high concentrations of IL-2 having a strict requirement for accessory cells for the development of lytic activity and proliferation. Accessory cells differed in their ability to activate T cells presumably depending on their ability to induce IL-2 synthesis, allogeneic dendritic cells being the most effective accessory cells and IL-2 synthesis stimulators. Allogeneic accessory cells could induce lytic activity in T cells even in the absence of exogenous IL-2. Thus, accessory cells play a central role in expanding the LAK effector cell population.

Antigen-Presenting Cells↗
PubMed1988

Both interleukin 1 and tumor necrosis factor enhance thymocyte proliferation.

One of the biological activities of interleukin 1 (IL1), the lymphocyte-activating function, is usually quantitated by measuring the effect on thymocyte proliferation in the presence of a T cell mitogen. Tumor necrosis factor (TNF) is also produced by activated macrophages, and it has recently been shown that it can enhance the proliferation of mature, human T cells. To analyze the role of these macrophage products in the proliferative response of murine thymocytes, we have tested the effects of purified (produced by the recombinant DNA techniques) IL1 and TNF in thymocyte cultures, where the cell concentration, mitogen as well as the accessory cell amount was varied. The data obtained show that both IL1 and TNF can facilitate the thymocyte proliferation, but the effect of TNF required a stronger T cell activation signal (a higher phytohemagglutinin, PHA, dose or concanavalin A instead of PHA) to become optimal. Moreover, the effect of IL1 was totally abolished by depleting the Ia+ accessory cells from the thymocytes, while that of TNF remained intact. IL1 and TNF acted synergistically in this activation and this effect was so strong that thymocyte proliferation started even in the absence of the mitogen. Thus, the data suggest that these cytokines act on different steps of the T cell activation process.

Animals↗
PubMed1988

Differential induction of membrane-associated interleukin 1 (IL-1) expression and IL-1 alpha and IL-1 beta secretion by lipopolysaccharide and silica in human monocytes.

Bacterial lipopolysaccharide (LPS) and silica dust are known to be effective inducers of interleukin 1 (IL-1) in human cultured monocytes. The data reported here show that although the levels of secreted IL-1 were equally high after in vitro stimulation with an optimal dose of LPS or silica, there were two clear differences: (i) the levels of membrane-associated IL-1 (as detected by the comitogenic effect of paraformaldehyde (PFA)-fixed cells or purified membrane fragments on murine thymocytes) were ca. five times higher after LPS stimulation than after silica stimulation, (ii) the secreted IL-1 after LPS stimulation was mainly of the pI 7 (IL-1 beta) type, while after silica stimulation there were equally high amounts of pI 7 and pI 5 (i.e. IL-1 alpha) forms. In both cases the IL-1 active molecules belonged to the 15 kDa class. These data show that the nature of the activating agent has a clear influence on the distribution of the biologically active IL-1 molecules. Moreover, the finding that after silica stimulation the amount of membrane-associated IL-1 (which was recently shown to be of the IL-1 alpha type) was low, while IL-1 alpha in the culture fluid was clearly elevated, suggests that the IL-1 alpha not attached to the cell membrane (or released from it) significantly contributes to the secreted IL-1 pool.

Cell Membrane↗
PubMed1988

Production of tumour necrosis factor and interleukin 1 by monocytes of patients with previous Yersinia arthritis.

We studied production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by using purified peripheral blood monocytes of patients with previous yersinia arthritis (YA) and of healthy HLA-B27 positive and negative controls. Lipopolysaccharide-exposed cells of HLA-B27 positive and negative patients, and those of HLA-B27 positive controls, generated significantly more TNF than did HLA-B27 negative control cells. There was a positive correlation between the levels of TNF and IL-1. Our results give credence to the view that augmented production of phlogistic mediators may contribute to inflammatory symptoms in patients with HLA-B27 associated disease.

Adult↗