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M Hurme

Publications and source records attributed to M Hurme.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interferon-gamma production in antigen specific T cell response: quantitation of specific mRNA and secreted protein.

Interferon gamma (IFN-gamma) production as a measure of cellular sensitization was studied by detection of the cytokine in culture supernatant by enzyme immunoassay (EIA) and by measuring cellular mRNA using the reverse transcriptase polymerase chain reaction (RT-PCR) method. These assays were compared to the standard lymphocyte proliferation assay as a marker of T cell responsiveness to foreign antigens. When blood donors seropositive for herpes simplex virus (HSV) were compared to seronegative donors, all measurements of cellular sensitization separated the groups without overlap. There were significant correlations between the IFN-gamma mRNA titre and the secreted IFN-gamma (r = 0.57, P = 0.03), and the proliferative response and the secreted IFN-gamma (r = 0.78, P = 0.001), as well as between the IFN-gamma mRNA titre and the proliferative response (r = 0.78, P < 0.001). When tetanus toxoid (TT) responses were studied in immunized subjects, a wide range of responsiveness could be seen and correlation between various measurements was poor. However, constant individual levels of the cytokine production were demonstrated. Six people who had received their last TT booster vaccination more than 5 years ago were revaccinated and repeatedly studied. An increase in the levels of produced IFN-gamma could be seen in all subjects and two who lacked a lymphocyte proliferation response developed it after revaccination.

Adult↗
PubMed1997

Oral cow milk challenge abolishes antigen-specific interferon-gamma production in the peripheral blood of children with atopic dermatitis and cow milk allergy.

BACKGROUND: A major feature of atopic dermatitis (AD) is the propensity to generate IgE to environmental antigens. Despite extensive information on IgE dysregulation in AD, the nature of immune responses to ingested allergens is poorly characterized. OBJECTIVE: To determine the clinical and immunological responses to food in AD patients. METHODS: To characterize the type and timing of clinical reactions to oral cow milk, 83 AD patients aged 2 to 60 months were subjected to double-blind placebo-controlled food challenge (DBPCFC). IFN-gamma and IL-4 production by their peripheral blood mononuclear cells (PBMC) was determined before and after DBPCFC. RESULTS: Of 50 patients positive to DBPCFC. 46% manifested exanthematous-type immediate-onset reactions and 54% eczematous-type late-onset reactions. In either group, the production of IL-4 and IFN-gamma by Concanavalin A-stimulated PBMC was comparable before and after DBPCFC. For immediate-reacting patients, the median IFN-gamma production by milk-stimulated PBMC was 11.5 (4.2-17.2) pg/ml as against 2.3 (0.2-5.7) pg/ml by unstimulated PBMC, P = 0.0008 before DBPCFC, and 4.6 (2.8-10.3) pg/ml. vs 4.2 (1.7-9.0) pg/mL, p = 0.40, correspondingly after DBPCFC. CONCLUSION: Before DBPCFC, immediate-reacting but not late-reacting patients were found to be capable of allergen-specific IFN-gamma production in vitro, indicating the heterogeneity in AD patients. After DBPCFC, the IFN-gamma generation abolished, indicating the effect of oral allergen exposure on IFN-gamma producing responses of AD patients.

Animals↗
PubMed1996

Naive (CD45RA+) T lymphocytes are more sensitive to oxidative stress-induced signals than memory (CD45RO+) cells.

Formation of reactive oxygen intermediates (ROI) after oxidative stress has been shown to be an activation signal for T lymphocytes, e.g., expression of IL-2 and its receptor are induced. These ROI-induced effects can, to a large extent, be attributed to the activation of the transcription factor NF-kappaB. Now we have examined whether naive and memory T lymphocytes differ in their sensitivity to ROI-mediated signals. When CD45RA+ (naive) and CD45RO+ (memory) T lymphocytes were directly stimulated with H2O2, NF-kappaB nuclear translocation was stronger in naive cells than in memory cells and it could be induced with lower doses. The composition of the induced nuclear NF-kappaB (levels of p50 and RelA proteins) was similar in these cell types. The magnitude and kinetics of intracellular ROI were similar, suggesting that there were no differences in ROI-forming mechanisms or antioxidative capacities. The probable regulatory point was the cytoplasmic IkappaB inhibitor: in CD45RA+ cells, H2O2 caused a more profound depression in the levels of IkappaB alpha. These findings indicate that T cells representing different activation and/or differentiation stages can be differentially responsive to ROI-mediated signals.

Adult↗
PubMed1996

Retinoic acid activates interferon regulatory factor-1 gene expression in myeloid cells.

All-trans-retinoic acid (ATRA) is the drug of choice in the treatment of acute promyelocytic leukemia (APL). ATRA induces both in vitro and in vivo differentiation of APL cells into mature granulocytes. However, the molecular mechanisms involved in ATRA-dependent growth inhibition and cellular differentiation are not presently understood. The NB4 cell line, which is derived from the bone marrow of a patient with APL during relapse, can be used as a model system to study the growth and differentiation of APL cells. Because interferon (IFN) regulatory factors (IRF-1 and IRF-2) and other IFN-inducible gene products regulate cell growth, we analyzed the effects of ATRA on the expression of these genes. We show that ATRA directly activates IRF-1 gene expression, followed by activation of IRF-2 and 2'-5' oligoadenylate synthetase (OAS) gene expression with slower kinetics. In addition to NB4 cells, ATRA also activated IRF-1 gene expression in HL-60, U937, and THP-1 cells, which all respond to ATRA by growth inhibition. A more than additive increase in IRF-1 gene expression was seen with ATRA and IFN-gamma in NB4 cells. ATRA did not activate nuclear factor kappa B or signal transducer and activator of transcription (STAT) activation pathways, suggesting that an alternate mechanism is involved in IRF-1 gene activation. The ATRA-induced expression of IRF-1, an activator of transcription and repressor of transformation, may be one of the molecular mechanisms of ATRA-induced growth inhibition, and the basis for the synergistic actions of ATRA and IFNs in myeloid leukemia cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

Down-regulation of anti-CD3 antibody-induced IL-4 production by bovine caseins hydrolysed with Lactobacillus GG-derived enzymes.

A prerequisite for systemic hyporesponsiveness to dietary antigens is their processing in the gut. This study investigated whether bovine caseins degraded by enzymes of an intestinal bacterial strain, Lactobacillus GG (ATCC 53103), could regulate the cytokine production by anti-CD3 antibody-induced peripheral blood mononuclear cells of 14 atopic patients, aged 5-29 (mean, 16) months. Purified casein up-regulated the interleukin-4 and interferon-gamma production, P = 0.008 and P = 0.008, respectively. Conversely, Lactobacillus GG-degraded casein down-regulated the interleukin-4 production, P = 0.003, with no effect on interferon-gamma. These results indicate that intestinal bacteria may modify immunomodulatory properties of native food proteins and introduce a promising tool to provide protection from potentially harmful dietary antigens at a young age.

Adolescent↗
PubMed1996

Activation of the protein kinase A increases the DNA-binding and transcriptional activity of c-Rel in T cells.

Cyclic AMP (cAMP)-dependent protein kinase A (PKA) is known to have both negative and positive effects on the activation mechanisms of T lymphocytes. The authors have analysed the effect of increased cAMP on the activation of NF-kappa B transcription factor. This factor controls the expression of several genes (e.g. IL-2 and IL-2 receptor) involved in the activation and proliferation of T cells. The authors found that elevation of intracellular cAMP in Jurkat T leukaemia cells activated with phorbol ester (PDBu)/calcium ionophore (A23187) increased the DNA-binding of NF-kappa B as detected by the electrophoretic mobility shift assay (EMSA). Analysis of the subunit composition of the DNA-binding complex indicated that the amount of c-Rel was enhanced while RelA was decreased. Analysis of the effect of elevated cAMP on the degradation of I kappa B-alpha and I kappa B-beta did not reveal an essential change in degradation kinetics of these inhibitor proteins. The elevation of cAMP did not increase the synthesis of c-Rel, but it enhanced the nuclear localization of this protein. Transfection of Jurkat cells with a plasmid kB/TK10-CAT indicated that the increased DNA-binding of c-Rel containing complexes seen in EMSA was also functional. These data imply that the strong and long-lasting c-Rel nuclear localization and DNA-binding induced by protein kinase A is not due to increased c-Rel synthesis or enhanced degradation of the I kappa B inhibitors. Therefore, a direct phosphorylation of the c-Rel protein is the most plausible explanation for these observations. Taken together, these results suggest that cAMP is able to regulate the expression of NF-kappa B-dependent genes in T cells by modifying the composition and subunit activity of NF-kappa B.

Base Sequence↗
PubMed1996

Signals leading to the activation of NF-kappa B transcription factor are stronger in neonatal than adult T lymphocytes.

The molecular background of the defects in the immune reactivity of human neonates has not been fully elucidated. As the NF-kappa B transcription factor has a central role in the control of transcription of several genes involved in immune and inflammatory responses, the authors have analysed the activation of NF-kappa B in human umbilical cord T lymphocytes. The activity was tested by quantitating the nuclear proteins binding to an oligonucleotide containing the consensus kappa B binding sequence (electrophoretic mobility shift assay). The data obtained demonstrate that phorbol dibutyrate/calcium ionophore A23187 (PDBu/iono) combination induced a clearly higher nuclear translocation of NF-kappa B in neonatal than adult T cells. This higher NF-kappa B activity was restricted to the CD4+ T-cell subset. Analysis of the nuclear extracts with antibodies directed against the major components of NF-kappa B the p50 and RelA (p65) proteins, indicated that the composition of NF-kappa B was similar in neonatal and adult cells. These results suggest that neonatal T cells are exposed to oxidative stress-inducing signals during delivery and/or are inherently more sensitive to NF-kappa B activating signals than adult T cells.

Adult↗
PubMed1996

Sleep-related disorders in carpal tunnel syndrome.

INTRODUCTION: Patients with carpal tunnel syndrome (CTS) often wake up at night due to pain and numbness of affected fingers and hand. We studied the sleep disorder caused by CTS. SUBJECTS AND METHODS: 34 consecutive patients referred for operative treatment of CTS answered to a sleep questionnaire and the results were compared to a stratified random sample of 1600 Finns aged 36-50 year, whose response rate to the mailed questionnaires was 75.2% (n = 1186). Six CTS patients underwent a polygraphic sleep study before and after operative treatment of CTS. RESULTS: CTS patients reported suffering from poor sleep quality, fragmentary sleep and daytime sleepiness more often than controls. Before operative treatment of CTS there were more nocturnal body movements (p < 0.01) and awakenings lasted longer (p < 0.05) than after operation. During preoperative sleep studies no drop in median nerve conduction was detected during awakenings. CONCLUSIONS: Patients with CTS suffer from fragmentary sleep. Although patients reported waking up for the pain or numbness of hands no impairment in median and ulnar nerve conduction could be observed during these awakenings. Operative treatment of hand entrapment significantly reduced the number of nocturnal movements.

Adult↗
PubMed1996

Bilateral Achilles tendon rupture: a report on two cases.

Two cases of traumatic bilateral Achilles tendon rupture are reported. One of the patients was a healthy middle-aged man, who had been an active national-level gymnast 20 years earlier. He had not suffered any complaints of Achilles tendons before. The ruptures occurred when, after a sauna, he showed his guests a vault forwards, which he had been able to perform easily. This time the landing took place on the toes, causing a high peak stretch to the calf muscles and Achilles tendons. The total rupture of both Achilles tendons was treated surgically, with an excellent result 2 days after the trauma. End-to-end suturation and a fascial flap plasty were made on both sides. No macroscopic degeneration could be detected on the rupture sites. He was allowed to walk freely 6 weeks after the surgery. The second case was a 54-year-old woman, who had suffered from Achilles tendinitis and peritendinitis for 2 years. Both tendons had been surgically treated, and severe adhesions and local degenerative changes had been found. The tendon rupture occurred when she injured her left ankle while getting out of the car. Two days later she fell at home, because of the weakness of the left side, and consequently the right Achilles tendon was injured. She was treated conservatively for 10 days, before the surgery was performed. Both tendons were ruptured and an extensive degeneration of the area was observed. The right side suffered from a rerupture, which was again treated surgically. After surgery the recovery was slow, but the final result 3 years later was moderate. Neither of the patients had any systemic diseases.

Achilles Tendon↗
PubMed1995

Activation of the signal transducer and transcription (STAT) signaling pathway in a primary T cell response. Critical role for IL-6.

The T cell activation is initiated by interaction of specific Ags with TCR, followed by activation of intracellular biochemical events leading to activation of several genes. The activation of signal transducer and activator of transcription (STAT) proteins in a primary TCR-mediated activation of T cells have been explored. In purified human peripheral blood T cells, nuclear STAT proteins were activated approximately 3 h after activation by cross-linked anti-CD3 Abs. These STAT proteins were detected by using the IFN-gamma-activated sequence (GAS) and related oligonucleotides as probes in electrophoretic mobility shift assay. Analysis of the nuclear extracts with anti-STAT Abs indicated that they contained STAT-3 and additional proteins crossreactive with the STAT family. The induction of STAT activity was inhibited completely by pretreatment with either cycloheximide or cyclosporin A, thus indicating that the induction was due to a secondary factor produced by the activated T cells. As neutralizing anti-IL-6 Abs effectively down-regulated the early induction of STAT proteins and as exogenously added IL-6 rapidly activated DNA binding similar to TCR-mediated bindings, it can be concluded that IL-6 is the factor responsible for the activation of STAT proteins in a primary T cell response.

Base Sequence↗
PubMed1995

Severe sciatica: a 13-year follow-up of 342 patients.

This study involved 342 patients hospitalized because of severe, persistent sciatica suggestive of a lumbar intervertebral disc herniation. After standard clinical evaluation, EMG and myelography, 220 patients underwent lumbar discectomy. The remaining 122 patients were treated conservatively. Follow-up examinations were arranged after 1, 5 and 13 years. The study focused on the rehabilitation outcome in general and differences in outcome between the two treatment groups. Several indicators showed a rather poor outcome for sciatica patients during the 13-year follow-up period. In the operated group 16% had been re-operated because of lumbar disc herniation. True recurrence of herniation (same level and side) occurred in 8%. In the conservatively treated group 14% had undergone spinal surgery. Nearly 70% of the patients still reported sciatica. Self-assessed levels of low back pain were "no change/worse" for 19% in the operated group and for 44% in the conservatively treated group. In both the study groups, nearly 40% of the subjects had retired on disability pensions.

Activities of Daily Living↗
PubMed1994

Comparison of retinoic acid and phorbol myristate acetate as inducers of monocytic differentiation.

Several human myeloid leukemia cell lines growing in vitro can be induced to differentiate to more mature monocyte/macrophage-like cells by treatment with protein kinase C-activating phorbol esters, such as PMA. In addition to PMA, cells of the THP-1 myeloid leukemia cell line acquire macrophage-like characteristics after treatment with all-trans retinoic acid (RA). To analyze the signal transduction mechanisms induced by RA, we first compared the effects of PMA and RA on the expression of genes which are known to be regulated during monocytic differentiation. Both RA and PMA effectively down-regulated c-myc expression, while c-myb expression decreased only after PMA treatment. Expression of the beta 2-integrin genes, CD11a and CD11b, was clearly increased after both of these treatments. Their effects on the src-family tyrosine kinase genes were different: hck expression was similarly induced by these agents but lyn expression was stronger and more rapid after RA treatment. RA also enhanced lyn mRNA production rapidly in HL-60, indicating that the activation of lyn gene expression is common in monocytic and granulocytic maturation of myeloid leukemia cells. To examine whether the AP-1 enhancer activity is involved in RA-induced monocytic differentiation, THP-1 cells were transiently transfected with a chloramphenicol acetyl transferase (CAT)-reporter gene containing 5 copies of the AP-1 binding sites. In contrast to PMA, RA did not induce any CAT activity in these cells, thus suggesting that the RA-induced changes in the expression of those genes described above were not dependent on the AP-1 enhancer activity.

CD18 Antigens↗
PubMed1994

Induction of differentiation of promyelocytic NB4 cells by retinoic acid is associated with rapid increase in urokinase activity subsequently downregulated by production of inhibitors.

13-trans retinoic acid (13-trans RA) is an effective inducer of differentiation of acute promyelocytic (APL) cells both in vivo and in vitro. It is used in the induction of remission of patients with APL. We found, by using the promyelocytic NB4 cell line established from a patient with APL, that the induction of differentiation with RA was accompanied by modulation of the plasminogen activation system. The expression of urokinase (uPA) activity was rapidly increased in the growth medium and at the surface of cells treated with RA. The high uPA activity was counteracted both in the growth medium and at the cell surface by an increased plasminogen activator inhibitor (PAI) production and reduction of uPA synthesis. The expression of uPA receptor and PAI-2 were stimulated and persisted at 48 hours from RA addition. The simultaneous induction of CD11b suggests that differentiation results in increased production of both. APL patients often encounter episodes of disseminated intravascular coagulation that are associated with secondary fibrinolytic events. Our results suggest that downregulation of uPA activity results in the decrease of plasmin on the surface of the differentiated cells, which may reduce the occurrence of fibrinolytic episodes of patients with APL.

Cell Differentiation↗
PubMed1994

Effect of interleukin-10 on NF-kB and AP-1 activities in interleukin-2 dependent CD8 T lymphoblasts.

Interleukin-10 is a multifunctional cytokine, which regulates the function of various cell types of the immune system. In CD8 T cells it is known to accelerate the interleukin-2 dependent proliferation and to induce the differentiation of these cells to active cytolytic cells. Now we have studied interleukin-10 induced intracellular signaling mechanisms in human interleukin-2 dependent CD8 T lymphoblasts. The data obtained demonstrate that interleukin-10 alone can activate the AP-1 transcription factor and potentiate the interleukin-2 induced NF-kappa B activity. Moreover, interleukin-10 induced a rapid tyrosine phosphorylation of several proteins. The pattern of proteins phosphorylated was very similar to that induced by interleukin-2. Together, these findings suggest that tyrosine kinase dependent activation of NF-kappa B and AP-1 transcription factors are involved in the signaling mechanism of interleukin-10. This activation pathway resembles that of interleukin-2 in the same cell type.

Base Sequence↗
PubMed1994

Plasma levels of interleukin-1 beta and interleukin-6 in schizophrenia, other psychoses, and affective disorders.

Plasma levels of interleukin (IL)-1 beta and IL-6 were measured in 60 acutely hospitalized psychiatric patients and in 60 healthy controls by enzyme-linked immunosorbent assay (ELISA). Almost no IL-6 was detected in the plasma of the patients or controls. The mean level of IL-1 beta was found to be significantly higher in schizophrenic patients than in their corresponding controls (P = 0.03). The acute schizophrenics, but not the group of chronic schizophrenics, contributed to this increase. No correlation with age, duration of illness or overt psychopathology was found. The neuroleptic medication did not prove to have a significant effect on the plasma IL-1 beta levels. There was no difference between non-psychotic affective disorder patients (N = 17) and the controls.

Adult↗
PubMed1994

Plasma and cerebrospinal fluid interleukin-1 beta and interleukin-6 in hospitalized schizophrenic patients.

Interleukin (IL)-1 beta and IL-6 levels in plasma and cerebrospinal fluid (CSF) of 14 medicated schizophrenic patients and 9 controls were measured by enzyme-linked immunosorbent assay. Almost no detectable levels of IL-6 in plasma or CSF from patients or controls were found. With regard to mean plasma or CSF levels of IL-1 beta there were no statistically significant differences between the two groups investigated. The dose of neuroleptic medication the patients used did not correlate with the IL-1 beta plasma levels. For the whole series of subjects (n = 23) or for the schizophrenic patients (n = 14) no correlation between the plasma and CSF levels of IL-1 beta was found.

Adult↗