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Biomedical subjects

M Hurme

Publications and source records attributed to M Hurme.

At least 19 recordsLinked to original sources
PubMed1992

Activin A/erythroid differentiation factor is induced during human monocyte activation.

Activin A/erythroid differentiation factor (EDF), a dimeric polypeptide hormone composed of two beta A subunits, regulates growth and erythroid differentiation of human hematopoietic progenitor and erythroleukemia cells. We have identified activated human peripheral blood monocytes as a natural source of activin A/EDF. In these cells, lipopolysaccharide (LPS) induced rapidly the expression of the beta A subunit mRNAs through protein kinase C-dependent transcriptional regulation. The beta A subunit mRNA expression was also increased by 1,25-dihydroxyvitamin D3, an inducer of macrophage maturation of monocytes. Western analysis with an anti-beta A antibody and an erythroid differentiation bioassay confirmed that the conditioned media of LPS-activated monocytes contained the activin A/EDF protein. We suggest that monocyte/macrophage-derived activin A/EDF may not only modulate hematopoiesis but may also act as a mediator molecule in the diverse physiologic and pathogenetic events in which these cells are involved.

Activins↗
PubMed1992

Measles virus infection enhances IL-1 beta but reduces tumor necrosis factor-alpha expression in human monocytes.

Monocytes may play a role in the immunologic abnormalities caused by measles. The effect of measles virus (MV) infection on peripheral blood monocyte functions is poorly known. We report that MV-infected PBM have an altered pattern of IL-1 beta and TNF-alpha production in response to stimulation with LPS and PMA in vitro. MV-infected peripheral blood monocytes produced higher amounts of IL-1 beta, whereas the production of TNF-alpha was reduced. The same effect was observed in the human monocytic cell line THP-1, which was used for RNA analysis. An increased steady-state level of IL-1 beta mRNA was observed in MV-infected cells, and the level of TNF-alpha mRNA was reduced. However, both IL-1 beta and TNF-alpha had about 50% increased transcription rate. Analysis of the mRNA stability after transcriptional block by actinomycin D showed that the TNF-alpha mRNA had a reduced half-life in MV-infected cells (about 30 vs 80 min in uninfected cells), whereas IL-1 beta mRNA stability was similar in uninfected and MV-infected cells. These results indicate that MV infection disturbs the immunoregulatory network by interfering with the monocyte functions.

Base Sequence↗
PubMed1992

ABO blood groups and musculoskeletal injuries.

The distribution of the ABO blood groups was studied in 917 patients with specific musculoskeletal diagnoses. The ABO blood group distribution of patients with rupture of the Achilles tendon (P = 0.030) and of patients with chronic Achilles peritendinitis (P = 0.10) differed from the controls. The ABO blood group distribution was not associated with other musculoskeletal injuries studied. The blood group A/O ratio was 1.42 in the control population. In the group with rupture of the Achilles tendon this ratio was 1.0, and in the group with Achilles peritendinitis it was 0.70. The association between injuries of the Achilles tendon and the ABO blood group distribution was in accordance with an earlier report. There may be a genetic linkage between the ABO blood groups and the molecular structure of the tissue of Achilles tendons.

Achilles Tendon↗
PubMed1992

Signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone.

Previous studies have shown that IL-8 gene expression is enhanced by various stimuli, which induce different signal transduction pathways. A lipopolysaccharide (LPS)-induced pathway has been reported to be inhibited by glucocorticoids in monocytes. We have now examined the effect of dexamethasone on the LPS-induced and other signal transduction pathways leading to the production of IL-8 by human monocytes. Dexamethasone inhibited the production of IL-8 stimulated with a cyclic adenosine monophosphate analog or LPS. In contrast, dexamethasone had no significant effect on a phorbol ester (PMA)-stimulated IL-8 production. These results suggest that the signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone.

Bucladesine↗
PubMed1992

Prolonged elevation of intracellular cyclic AMP activates interleukin-1 production in human peripheral blood monocytes.

The capability of elevated intracellular cyclic AMP concentration to activate IL-1 gene expression and protein production was examined in human peripheral blood monocytes. In accordance with previous studies it was observed that the transiently elevated cyclic AMP (induced either with prostaglandin E2 or with the direct adenylate cyclase activator, forskolin) was not a sufficient signal to activate IL-1 production. However, if the degradation of cyclic AMP was inhibited with isobutyl-methyl-xanthine (IBMX), IL-1 production was strongly activated. This prostaglandin E2 plus IBMX effect could also be mimicked with high concentrations of the cell permeant structural cyclic AMP analogue, dibutyryl cyclic AMP. The cyclic AMP-induced IL-1 production differed in some aspects from the bacterial lipopolysaccharide-induced IL-1 production: (1) the kinetics of both IL-1 gene expression and protein production was much slower; (2) the IL-1 beta gene expression was superinducible by inhibiting the protein synthesis with cycloheximide. Thus these data suggest that prolonged elevation of cyclic AMP is alone a sufficient signal to activate IL-1 production.

Blotting, Northern↗
PubMed1992

The effect of calcium mobilization on LPS-induced IL-1 beta production depends on the differentiation stage of the monocytes/macrophages.

The role of elevated intracellular calcium concentration [Ca2+]i in the LPS-induced activation of interleukin-1 beta (IL-1 beta) production was examined in cells representing different stages of myeloid differentiation (undifferentiated monocytic leukaemia cell line THP-1, THP-1 cells induced to adherent, macrophage-like cells by phorbol ester treatment and normal peripheral blood-derived adherent monocytes). LPS did not elevate the [Ca2+]i as measured by the Fura-2 fluorescence technique. When these cells were stimulated with LPS in the presence of the calcium ionophore A23187, a clear increase in the IL-1 beta protein production was observed in the undifferentiated THP-1 cells but not in the more differentiated cell types. This ionophore-induced increase was also seen in the IL-1 beta mRNA levels. Thus these data confirm the previous findings demonstrating that elevation of [Ca2+]i is not involved in the LPS-dependent signal transmission. However, the LPS-induced signals are greatly potentiated by the elevated [Ca2+]i, but only in undifferentiated monocytic cells.

Calcimycin↗
PubMed1991

Regulation of interleukin-1 beta production by glucocorticoids in human monocytes: the mechanism of action depends on the activation signal.

Glucocorticoids are known to downregulate interleukin-1 beta production in monocytic cells by two different mechanims: direct inhibition of the gene transcription and destabilization of the preformed interleukin-1 beta mRNA. Now we have examined the effect of the nature of the monocyte activating signal on these two inhibitory mechanims. When human monocytes were preincubated with dexamethasone for 1 hour and then stimulated either with bacterial lipopolysaccharide or phorbol myristate, it was found that dexamethasone inhibited the lipopolysaccharide-induced interleukin-1 beta protein production, but the phorbol myristate-induced production was increased 3-10 fold. This difference was also seen at the mRNA level. When dexamethasone was added to the cultures 3 hours after the stimulators, it clearly decreased the interleukin-1 beta mRNA levels regardless of the stimulator used (although the effect was clearly weaker on the PMA-induced mRNA). Thus these data suggest that the phorbol myristate-induced signal (prolonged protein kinase C activation?) cannot be inhibited by prior incubation with dexamethasone and it also protects the induced mRNA for the degradative action of dexamethasone.

Cells, Cultured↗
PubMed1991

Retinoic acid enhances IL-1 beta expression in myeloid leukemia cells and in human monocytes.

We have examined the role of retinoic acid (RA), the biologically active metabolite of vitamin A, in expression of the IL-1 beta gene in the human myeloid leukemia cell line THP-1 and in human monocytes. Both protein kinase C-activating phorbol esters, e.g., PMA, and LPS induce IL-1 beta expression in these cells. Physiologic RA concentrations alone were not able to induce any IL-1 beta production, but they strongly enhanced the PMA-induced IL-1 beta protein production and mRNA accumulation in both human monocytes and in THP-1 cells. Nuclear run-off analysis revealed that the enhancing effect was at the transcriptional level. RA also slightly potentiated LPS-induced IL-1 beta expression in THP-1 cells but not in human monocytes. These data suggest that RA can be a strong up-regulator of IL-1 production, but its strength varies depending on the nature of the activating signal.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Restoration of patellofemoral congruity by combined lateral release and tibial tuberosity transposition as assessed by MRI analysis.

Twelve knees in eleven patients with subluxation or dislocation of the patella were assessed by MRI at 0, 10, 20 and 30 degrees of knee flexion, before and after vastus lateralis release and medial transplant of the tibial tuberosity. The preoperative position of the patella deviated the greatest from normal in 0-20 degrees of knee flexion. The operations were found to correct the lateral patellofemoral angle and the lateral patella tilt with or without quadriceps muscle contraction, but did not completely correct the marked preoperative lateral patellar displacement and tracking.

Adult↗
PubMed1991

Clinical findings as outcome predictors in rehabilitation of patients with sciatica.

In rehabilitation of patients with sciatica, factors prognostic of long-term outcome could prove beneficial in interventions and in evaluating progress toward fitness or capacity for work. In this study results of physical examinations, carried out one year after hospital treatment for suspected lumbar intervertebral disc herniation, were related to outcome after five-years, as assessed by the categorization of occupational handicap of the International Classification of Impairments, Disabilities and Handicaps (ICIDH). The sample consisted of 276 patients admitted to hospital in the years 1980-1982. Based on established clinical indications 179 patients underwent lumbar disc surgery and the remaining 97 received further conservative treatment. One year after hospitalization a physician and physiotherapist examined the patients at the Rehabilitation Research Centre (RRC) of the Social Insurance Institution in Finland. In 1986 the patients returned to the RRC for further evaluation of their occupational handicap at that time. Stepwise logistic regression analysis showed that sensory deficits of legs, tenderness in lumbar extension, decreased repetitive trunk flexion performance (sit-up test), decreased lumbar lordosis and tightness of hamstrings were indicative of a poor outcome in the operated group. For the non-operated patients no statistically acceptable regression analysis model could be established.

Adult↗
PubMed1991

Cyclic adenosine monophosphate decreases the secretion, but not the cell-associated levels, of interleukin-1 beta in lipopolysaccharide-activated human monocytes.

Interleukin-1 beta (IL-1 beta) is a cytokine produced mainly by activated monocytes though the mechanism by which it is released is still unknown. Elevation of intracellular cyclic adenosine monophosphate (cAMP) is considered an important down-regulative signal in the production of IL-1 beta in lipopolysaccharide (LPS)-induced monocytes. In this study we show that in LPS-activated human monocytes, elevated cAMP concentrations (induced by either prostaglandin E2, forskolin or dibutyrylcyclic AMP) affected specifically secretion of IL-1 beta; the amount of secreted IL-1 beta was clearly reduced whereas the cell-associated level remained unchanged. TNF-alpha, a normal secretory protein, was used as a control. Cyclic AMP also inhibited TNF production by monocytes, but the decrease was of the same magnitude in the extracellular and intracellular compartments. Thus, the down-regulative effect of cAMP on the production of these monokines is clearly different.

Bucladesine↗
PubMed1991

Different activation signals are required for the expression of interleukin-1 alpha and beta genes in human monocytes.

The production and mRNA expression of IL-1 alpha and IL-1 beta by human monocytes was examined after two different stimuli, a protein kinase C (PKC) activator phorbol myristate acetate (PMA) and bacterial lipopolysaccharide (LPS). LPS induced production of high levels of both IL-1 alpha and IL-1 beta protein (quantitated with type-specific ELISA assays), while after PMA stimulation only IL-1 beta protein could be detected. The IL-1 alpha and IL-1 beta mRNA levels quantitated by Northern blotting were in line with the respective protein levels and nuclear run off analysis revealed that PMA did not activate the IL-1 alpha transcription. The production of the IL-1 alpha and IL-1 beta protein as well as the mRNA expression could be inhibited with protein kinase inhibitor H7, but not with HA1004, indicating that PKC activation is essential for the activation of these genes. Thus these data indicate that PKC activation alone is sufficient for the induction of the IL-1 beta gene, but some additional signals (provided by LPS) are required for the activation of the IL-1 alpha gene.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Social factors and outcome in a five-year follow-up study of 276 patients with sciatica.

Social factors of 179 operated and 97 non-operated patients one year after hospitalization due to low back pain and sciatica were tested by multi-variate regression analysis in relation to the five-year outcome evaluated according to the WHO Handicap Classification. For operated men a subjective working incapacity (relative risk RR = 4.6) and co-morbidity (RR = 2.7) predicted a poor outcome. For operated women the predictive factors were subjective working incapacity (RR = 3.2) and older age (RR = 1.9). For non-operated men an increased occurrence of occupational hazards (RR = 3.6) and for non-operated women co-morbidity (RR = 7.1) indicated a poor outcome.

Adult↗
PubMed1991

CT five years after myelographic diagnosis of lumbar disk herniation.

Fifty-seven patients were examined with CT 5 years after primary myelography for disabling sciatica and suspected herniated lumbar disk. Forty were in an operated group, 22 with good and 18 with poor results evaluated by occupational handicap (21) 5 years after surgery. Seventeen patients had myelography indicating disk herniation, but were treated conservatively, 9 with good and 8 with poor result. Various spinal dimensions measured at CT did not correlate with outcome. Operated patients had narrower canals than others, and male canals were broader than those in females. Increased amount of scar tissue at L4 level correlated with poor result (p = 0.008). Operated patients with poor result had more advanced lateral stenosis than those treated conservatively (p less than 0.001). Patients with good result after operation had more degeneration observed on CT of erector spinae muscle than those treated conservatively with good outcome. Only 9% of operated patients did not have muscle degeneration. A tendency for more frequent recurrent disk herniations could be seen for conservatively treated patients. The narrowing of the spinal canal 5 years after operation did not correlate with the 5-year outcome.

Adult↗
PubMed1990

Control of interleukin-1 beta expression by protein kinase C and cyclic adenosine monophosphate in myeloid leukemia cells.

We have examined the signal transduction pathways leading to the expression of the interleukin-1 beta (IL-1 beta) gene in human myeloid leukemia cells lines. Two cell lines representing different stages of differentiation were used (HL-60, promyelocytic, and THP-1, mature monocytic). In accordance with previous studies, it was observed that a protein kinase C (PKC) activator, phorbol myristate acetate (PMA), was a sufficient stimulus for induction of the IL-1 beta messenger RNA (mRNA) expression and IL-1 beta protein production in both of these cell lines. A structural analog of cyclic adenosine monophosphate (dbcAMP) or agents elevating the endogenous cAMP levels (prostaglandin E2, forskolin) were not alone able to induce IL-1 beta expression, but they strongly enhanced the PMA-induced IL-1 beta production and IL-1 beta mRNA accumulation. Nuclear run off analysis showed that this elevation in IL-1 beta mRNA levels was due to an increased rate of transcription. If dbcAMP was added 6 hours before PMA to the cultures, no enhancement in the IL-1 beta production was seen, implying that for this enhancing effect both of these signals must be present simultaneously. PKC inhibitor, H7, also blocked effectively the PMA plus dbcAMP induced IL-1 beta production, while the protein kinase A (PKA) inhibitor, HA1004, had no effect, suggesting that PKA activation is not involved in the mechanism of action of cAMP in this case. Collectively, the present findings show that cAMP-dependent signals can have a positive regulatory effect on the PKC-dependent activation of the IL-1 beta gene in cells derived from different stages of myeloid differentiation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Growth inhibition caused by serum depletion induces differentiation, interleukin 1 receptor expression and interleukin 1 responsiveness in the HL-60 promyelocytic leukemia cell line.

The role of interleukin-1 (IL-1) was studied in the proliferation of promyelocytic HL-60 leukemia cells. When HL-60 cells were cultured in 10% fetal calf serum (FCS) containing medium IL-1 did not have any effect on the proliferation. In 1% FCS containing medium, the proliferation of HL-60 cells gradually decreased, but IL-1 was found to be clearly mitogenic for these cells. IL-1 did not function as an autocrine growth factor for HL-60 cells, since anti-IL-1 antibodies did not suppress the basal proliferation of these cells. IL-1 was also mitogenic for U937 but not for THP-1 cells. The suppression of HL-60 proliferation was found to be accompanied with monocytic differentiation as assessed by an increase in HLA-DR, CD11b and CD14 antigen expression. IL-1 could suppress this differentiation. HL-60 cells cultured in 1% FCS were found to express increased amounts of IL-1 receptors on the cell surface.

Antigens, Differentiation↗
PubMed1990

Modulation of interleukin-1 beta production by cyclic AMP in human monocytes.

Elevation of cAMP has been considered to be an important downregulative signal in the production of interleukin-1(IL-1). This study demonstrates that this phenomenon is dependent on the signal used to activate the IL-1 production. The IL-1 beta production of lipopolysaccharide activated human monocytes was readily inhibited by dibutyryl cAMP. This took place without a significant change in the steady-state levels of IL-1 beta mRNA. By contrast, in PMA activated monocytes 100 microM dibutyryl cAMP increased in IL-1 beta production ca. 4-fold. The steady-state levels of IL-1 beta mRNA were also simultaneously increased.

Bucladesine↗