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At least 667 records · Page 37Linked to original sources
PubMed1995

The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is exerted at the transcriptional level.

The combination of interleukin 6 (IL-6) and interleukin 1 (IL-1) synergistically induces the human acute-phase reactant, C-reactive protein (CRP) in Hep3B cells. While previous studies have indicated that IL-6 induces transcription of CRP, the mode of action of IL-1 has not been clearly defined. It has been suggested that the effect of IL-1 might be post-transcriptional, exerted through the 5'-untranslated region (5'-UTR). To evaluate the role of IL-1 in CRP gene expression, we studied the effects of interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) on both the endogenous CRP gene and on transfected CRP-CAT constructs in Hep3B cells. In kinetic studies of the endogenous CRP gene, IL-1 beta alone had no effect on CRP mRNA levels, but when added to IL-6, synergistically enhanced both CRP mRNA levels and transcription, as determined by Northern-blot analyses and nuclear run-on studies. IL-6 alone and the combination of [IL-1 beta + IL-6] each induced increases in mRNA levels roughly comparable with observed increases in transcription. These findings indicate that the effect of IL-1 beta on CRP expression is exerted largely at the transcriptional level in this system. This conclusion was confirmed by studies in Hep3B cells transiently transfected with CRP-CAT constructs, each containing 157 bp of the CRP 5'-flanking region but differing in the length of the 5'-UTR from 104 bp to 3 bp. All constructs responded in the same way; IL-6, but not IL-1 beta, induced significant chloramphenicol acetyltransferase (CAT) expression which was synergistically enhanced 2- to 3-fold by IL-1 beta. These results indicate that IL-1 beta stimulates transcriptional events in the presence of IL-6 and that the upstream 157 bases of the CRP promoter contain elements capable of both IL-6 induction and the synergistic effect of IL-1 beta on transcription.

C-Reactive Protein↗
PubMed2001

Neurochemical and electrophysiological evidence that 5-HT4 receptors exert a state-dependent facilitatory control in vivo on nigrostriatal, but not mesoaccumbal, dopaminergic function.

In this study we investigated, using in vivo microdialysis and single unit recordings, the role of serotonin4 (5-HT4) receptors in the control of nigrostriatal and mesoaccumbal dopaminergic (DA) pathway activity. In freely moving rats, the 5-HT4 antagonist GR 125487 (1 mg/kg, i.p.), without effect on its own, significantly reduced the enhancement of striatal DA outflow induced by 0.01 (-35%) and 0.1 (-66%), but not 1 mg/kg, s.c. haloperidol (HAL). Intrastriatal infusion of GR 125487 (1 microM) had no influence on basal DA outflow, but attenuated (-49%) the effect of 0.01 mg/kg HAL. Systemic administration of GR 125487 modified neither basal nor 0.01 mg/kg HAL-stimulated accumbal DA outflow. In halothane-anaesthetized rats, 1 or 10 mg/kg GR 125487, without effect by itself, failed to modify the changes in accumbal and striatal DA outflow elicited by electrical stimulation (300 microA, 1 ms, 20 Hz, 15 min) of the dorsal raphe nucleus. Finally, GR 125487 (444 microg/kg, i.v.), whilst not affecting basal firing of DA neurons within either the substantia nigra or the ventral tegmental area, reduced HAL-stimulated (1--300 microg/kg, i.v.) impulse flow of nigrostriatal DA neurons only. These results indicate that 5-HT4 receptors exert a facilitatory control on both striatal DA release and nigral DA neuron impulse flow only when nigrostriatal DA transmission is under activated conditions. Furthermore, they indicate that the striatum constitutes a major site for the expression of the control exerted by 5-HT4 receptors on DA release. In contrast, 5-HT4 receptors have no influence on mesoaccumbal DA activity in either basal or activated conditions.

Action Potentials↗
PubMed2001

Ectoderm exerts the driving force for gastrulation in the sand dollar Scaphechinus mirabilis.

How the ectodermal layer relates to the invagination processes was examined in the sand dollar Scaphechinus mirabilis. When the turgor pressure of blastocoele was increased, invagination was completely blocked. In contrast, an increase in turgor pressure did not affect elongation of the gut rudiment in the regular echinoid Hemicentrotus pulcherrimus. Rhodamine-phalloidin staining showed that the distribution of actin filaments was different between two species of embryos. In S. mirabilis gastrulating embryos, abundant actin filaments were seen at the basal cortex of ectoderm in addition to archenteron cells, while the intense signal was restricted to the archenteron in H. pulcherrimus. To investigate whether actin filaments contained in the ectodermal layer exert the force of invagination, a small part of the ectodermal layer was aspirated with a micropipette. If S. mirabilis embryos were aspirated from the onset of gastrulation, invagination did not occur at all, irrespective of the suction site. Even after the archenteron had invaginated to one-half of its full length, further elongation of the archenteron was severely blocked by suction of the lateral ectoderm. In contrast, suction of the ectodermal layer did not affect the elongation processes in H. pulcherrimus. These results strongly suggest that the ectodermal layer, especially in the vegetal half, exerts the driving force of invagination in S. mirabilis.

Actin Cytoskeleton↗
PubMed2002

Erythropoietin exerts anti-apoptotic effects on rat microglial cells in vitro.

Erythropoietin (EPO), a renal cytokine regulating haematopoiesis, is also produced by different cell types within the central nervous system, where it acts via the activation of specific receptors. Current evidence shows that EPO exerts neurotrophic and neuroprotective activities in different in vivo and in vitro models of brain damage. In the present study we investigated the effects of EPO on primary cultures of rat cortical microglia and astrocytes. We found that: (i) EPO exerted a marked stimulatory effect on microglial cell viability, assessed through the MTS assay, whereas astrocytes were almost unaffected; (ii) the cytokine increased microglial cell population size in a concentration-dependent manner; however, as microglia cultures undergo spontaneous apoptosis after separation from astrocytes, the apparent effect on cell proliferation could be attributed to EPO antagonism of normal apoptosis; (iii) subsequent flow cytometry analysis on microglial cells demonstrated both the trophic role of factor(s) released by astrocytes in mixed cultures, and the putative anti-apoptotic action of EPO; (iv) the latter was further confirmed through the assessment of gene expression of anti- and pro-apoptotic factors, which showed that EPO is able to shift the Bcl : Bax ratio towards a net anti-apoptotic effect; (v) EPO did not affect the pro-inflammatory function of microglial cells.

Animals↗
PubMed2002

Spontaneous CSF leaks mimicking benign exertional headaches.

Spontaneous CSF leaks are increasingly recognized, and a broader clinical and imaging spectrum of the disorder is emerging. The headaches of CSF leaks are typically orthostatic, but sometimes especially with chronicity the orthostatic features are blurred into lingering chronic daily headaches. Additional types of headache are also increasingly recognized. Two patients with spontaneous CSF leaks presented with intermittent transient severe headaches provoked by Valsalva-type manoeuvres. Orthostatic features were absent and the patients were asymptomatic if they avoided the provoking manoeuvres. One patient had been treated for 6 years for benign exertional headaches and had failed many medical treatments, including courses of indomethacin. He was found to have a leak from cribriform plate. The second patient had been symptomatic for several months, had diffuse pachymeningeal gadolinium enhancement on head magnetic resonance imaging, spinal meningeal diverticula, and CSF leak at the thoracic spine level. Headaches that mimic benign exertional headaches are yet another mode of the still broadening clinical presentation of spontaneous CSF leaks.

Adult↗
PubMed2002

Exertional headache. I. Vågå study of headache epidemiology.

The aim was to assess the prevalence ('life-time') and manifestations of exertional headache and to validate some of the clinical diagnostic criteria. This study is part of the Vågå headache epidemiology study, where 1838 18-65-year-old dalesmen were personally examined in a 'semistructured' interview. With the criteria used, the prevalence was 12.3%. There was a slight but significant female preponderance (F/M ratio 1.38). There was a mixture of short- and more long-lasting attacks. Attacks followed long-lasting and strenuous effort/exhaustion. The precipitation mechanisms differed essentially from the cough/sneezing type of provocation. Blinded recheck of records (n = 100) as well as recheck of dalesmen (n = 41) showed high kappa values. The clinical manifestations differed essentially from Rooke's (1968) description (that mainly dealt with the 'cough headache'-type). The present findings were similar to those in Pascual's description of exertional headache from 1996.

Adolescent↗
PubMed2001

Validation of a rating scale of perceived exertion in young children.

The aim of this study was to develop and validate a scale rating the perceived exertion of young children (RPE-C) who do not read. This scale presents seven pictures showing a man who becomes progressively fatigued. In order to evaluate this scale, we examined its reliability and sensitivity. Thirteen children (aged 5 to 6 years) completed two identical incremental maximal running trials during a period of one week. A group of 12 adolescents and a group of 12 adults also tested the RPE-C by performing one trial under the same experimental conditions as the child group. RPE-C was recorded at the end of each load level. Statistical analysis revealed significant effects for velocity (F = 23.98, p < 0.0001) with non-significant effects for the trials. Intraclass correlation coefficient (ICC) revealed an acceptable reliability of RPE-C at low and high exercise intensities but also showed a low reliability at intermediate load levels (0.17 < ICC < 0.77). A significant correlation between RPE-C and heart rate (r2 = 0.61, p < 0.0001) was observed in children. However, the r2 level was lower than that observed for the adolescent or adult groups. This finding demonstrates the sensitivity of RPE-C to discriminate the effects of age on perceived exertion. RPE-C seems to be a good tool which can be used in young children to monitor exercise performed at low and high intensities.

Age Factors↗
PubMed1993

Displacement-clamp measurement of the forces exerted by gating springs in the hair bundle.

Mechanical stimuli applied to the hair bundle of a hair cell are communicated to the transduction channels by gating springs, elastic elements that are stretched when the bundle is displaced toward its tall edge. To quantify the magnitude and time dependence of the forces exerted by gating springs, we have developed a displacement-clamp system that constrains a bundle's motion while measuring the forces that the bundle produces during adaptation to mechanical stimuli, in response to channel blockage, and upon destruction of the gating springs. Our results suggest that each gating spring exerts a tension of approximately 8 pN in the resting bundle and can sustain at least 4-13 pN of additional tension. The experiments provide further evidence that the gating springs account for at least one-third of the hair bundle's dynamic stiffness and that a force of approximately 100 fN is sufficient to open a single transduction channel.

Animals↗
PubMed2000

Paxillin alpha and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation.

Protein tyrosine phosphorylation accompanies and is essential for integrin signaling. We have shown that tyrosine phosphorylation of paxillin alpha and Crk-associated substrate (p130(Cas)) is a prominent event on integrin activation in normal murine mammary gland epithelial cells. Tyrosine phosphorylation of p130(Cas) has been demonstrated to facilitate cell migration. We show here that tyrosine phosphorylation of paxillin alpha acts to reduce haptotactic cell migrations as well as transcellular invasive activities in several different experimental cell systems, whereas tyrosine phosphorylation of p130(Cas) exerts opposing effects to those of paxillin alpha. Each of the phosphorylation-null mutants acts as a dominant negative for each phenotype. Moreover, we found that overexpression of paxillin alpha reduced the cell saturation density of normal murine mammary gland cells, whereas overexpression of p130(Cas) increased it. These effects also seemed to depend on tyrosine phosphorylation events. Cell growth rates and morphologies at growing phases were not significantly altered, nor were cells transformed. Addition of epidermal growth factor increased saturation density of the paxillin alpha-overexpressing cells, whereas no further increment was observed in p130(Cas)-overexpressing cells. We propose that tyrosine phosphorylation of paxillin alpha and p130(Cas) exerts opposing effects on several integrin-mediated cellular events, possibly through different signaling pathways.

Animals↗
PubMed2003

Parathyroid hormone-Smad3 axis exerts anti-apoptotic action and augments anabolic action of transforming growth factor beta in osteoblasts.

Although several studies indicated that parathyroid hormone (PTH) exerted anabolic action on bone, its precise mechanisms have been unknown. On the other hand, transforming growth factor beta (TGF-beta), abundantly stored in bone matrix, stimulates bone formation with a local injection in rodents. Although our previous study suggested that Smad3 is an important molecule for the stimulation of bone formation, no reports have been available about the effects of PTH on Smad3. In this present study, we examined the effects of PTH on Smad3 and the physiological significance in mouse osteoblastic cells. PTH promoted the expression of Smad3 mRNA within 10 min and the protein level in a dose-dependent manner in MC3T3-E1 and rat osteoblastic UMR-106 cells. Protein kinase A (PKA) activator as well as protein kinase C (PKC) activators increased Smad3 protein level, and both PKA and PKC inhibitors antagonized PTH-induced Smad3, indicating that PTH promotes the production of Smad3 through both PKA and PKC pathways. Next, we examined anti-apoptotic effects of PTH and Smad3 in these cells, employing trypan blue, transferase-mediated nick end labeling, and Hoechst staining. Pretreatment with PTH or overexpression of Smad3 decreased the number of apoptotic cells induced by dexamethasone and etoposide. Moreover, a dominant negative mutant, Smad3DeltaC, abrogated PTH-induced anti-apoptotic effects. On the other hand, PTH augmented TGF-beta-induced transcriptional activity. Furthermore, PTH enhanced TGF-beta-induced production of type I collagen, whereas it did not affect TGF-beta-reduced proliferation in MC3T3-E1 cells. These observations indicated that PTH amplified the anabolic effects of TGF-beta by accelerating the transcriptional activity of Smad3. In conclusion, we first demonstrated that PTH-Smad3 axis exerts anti-apoptotic effects in osteoblasts and reinforces the anabolic action by TGF-beta in osteoblasts. Hence, PTH-Smad3 axis might be involved in the bone anabolic action of PTH.

Animals↗
PubMed2001

Spinal shrinkage during repetitive controlled torsional, flexion and lateral bend motion exertions.

This experiment analysed the spinal shrinkage due to repetitive exertions confined to each of three separate axes (twist, lateral bend, flexion). While the experiment was performed twice with small technique modifications in the twisting task (and thus two data collections were performed), the essential components were as follows. A total of 20 subjects were loaded with an equal moment of 20 Nm in each of the three axes, on 3 separate days (one axis per day). Subjects performed each task for 20 min at 10 repetitions min(-1), where stadiometer measurements of standing height were taken prior to and immediately following the 20 min exertion. The twisting task demonstrated significant spinal shrinkage (1.81 and 3.2 mm in the two experiments) between the pre- and post-stature measurements while no clear effect emerged for the other two tasks. These data suggest that repetitive torsional motions impose a larger cumulative loading on the spine when compared with controlled lateral or flexion motion tasks of a similar moment.

Adult↗
PubMed1997

Force exertion in awkward working postures--strength capability while twisting or working overhead.

Isometric strength data have been collected for three of the awkward work situations often imposed by workplace constraints in industry, as found in jobs such as maintenance and repair. The effects of the task layout factors (location of the workpiece, reach distance and direction of force exertion) were investigated and the data has been tabulated to show the degree to which strength may be reduced in different situations. Strength measurements in the present study were found to be considerably higher than previous measurements, apparently due to differences in instructions on foot placement that were given to subjects, which indicates that even small constraints on posture within the workplace may have large effects on the ability to exert force.

Adult↗
PubMed2002

L-carnitine does not exert any in vitro relaxant effect in Guinea pig trachea, lung parenchyma and human bronchial tissue.

The aim of the present study was to investigate the probable in vitro relaxant effect of carnitine in guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissue. It was suggested by an in vivo study that carnitine pretreatment prevented the subclinic bronchospasm in children who underwent chronic hemodialysis. Tracheal and lung parenchymal preparations of 10 guinea pigs and 5 human bronchial tissues were prepared and mounted in 20-mL organ baths. In the first series of experiments, contractions to carbachol and histamine (10(-9) to 10(-3) M) were compared after the tissues were incubated with different concentrations of L-carnitine (10(-6) to 10(-4) M). pD(2) values were compared with analysis of variance (ANOVA) and P <.05 was considered as significant. In the second part of experiments, the inhibitory effect of L-carnitine (10(-9) to 10(-3) M) was investigated on the sustained contractions of preparations to carbachol (10(-6) M) and histamine (10(-5) M). In the first part of the study pD(2) values obtained with carbachol were 6.48 +/- 0.09, 5.42 +/- 0.05, and 6.48 +/- 0.02 for guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissues, respectively. pD(2) values obtained with histamine were 5.34 +/- 0.10, 5.74 +/- 0.06, and 6.32 +/- 0.03 for guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissues, respectively. No significant difference was observed between the pD(2) values before and after incubation with carnitine (P >.05). In the second part of the study, only 10(-4) M L-carnitine exerted an insignificant relaxant effect (6.16% +/- 1.22% on carbachol induced contractions and 4.48% +/- 0.85% on histamine induced contractions) in guinea pig trachea. Our results show that L-carnitine exerts no in vitro relaxant effect in guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial preparations.

Animals↗
PubMedDate not supplied

The influence of knife dullness on poultry processing operator exertions and the effectiveness of periodic knife steeling.

A novel procedure is described to establish knife steeling schedules for poultry and meat- processing operations based on increased force due to knife dullness from repetitive use to minimize operator exertions and physical stress associated with work-related musculoskeletal disorders. Knife dullness was quantified using a novel apparatus described in this article that measures the area cut by a knife into a carrageenan gel target for a controlled dynamic load at the knife handle. Two meat-cleaning jobs in a poultry-processing plant were studied. One job required significantly more force and a greater number of cuts than the other. Eight experienced operators participated in the study. Four freshly ground and honed knives were randomly used by each operator for 4, 45, 75, or 125 cutting cycles, measured for dullness and reconditioned by the operator using a steel sharpening rod. An empirical model for knife dulling and reconditioning was developed, and the corresponding increase in force was predicted for various cutting and reconditioning frequencies. The model showed that it took 57 and 125 cutting cycles for the high- and low-force jobs, respectively, to achieve a similar reduction in target surface area of 30%. This reduction in target surface area corresponded to a similar percentage increase in force needed for the same cut in carrageenan gel as compared to a freshly honed knife as measured using strain gages. This method may be used in meat processing plants for determining effective reconditioning schedules that reduce operator exertions with minimum effect on quality and productivity.

Adult↗
PubMed1996

Kinetochores moving away from their associated pole do not exert a significant pushing force on the chromosome.

We used video-light microscopy and laser microsurgery to test the hypothesis that as a bioriented prometaphase chromosome changes position in PtK1 cells, the kinetochore moving away from its associated pole (AP) exerts a pushing force on the centromere. When we rapidly severed congressing chromosomes near the spindle equator between the sister kinetochores, the kinetochore that was originally "leading" the motion towards a pole (P) always (17/17 cells) continued moving P whereas the "trailing" kinetochore moving AP always stopped moving as soon as the operation was completed. This trailing kinetochore then initiated motion towards the pole it was originally moving away from up to 50 s later. The same result was observed (15/15 cells) when we selectively destroyed the leading (P moving) kinetochore on a congressing chromosome positioned > or = 3 microns from the pole it was moving away from. When we conducted this experiment on congressing chromosomes positioned within 3 microns of the pole, the centromere region either stopped moving, before switching into motion towards the near pole (2/4 cells), or it continued to move AP for 30-44 s (2/4 cells) before switching into P motion. Finally, kinetochore-free chromosome fragments, generated in the polar regions of PtK1 spindles, were ejected AP and often towards the spindle equator at approximately 2 microns/min. From these data we conclude that the kinetochore moving AP on a moving chromosome does not exert a significant pushing force on the chromosome. Instead, our results reveal that, when not generating a P force, kinetochores are in a "neutral" state that allows them to remain stationary or to coast AP in response to external forces sufficient to allow their K-fiber to elongate.

Animals↗
PubMed2000

Molecular evidence of greater selective pressure for drug resistance exerted by the long-acting antifolate Pyrimethamine/Sulfadoxine compared with the shorter-acting chlorproguanil/dapsone on Kenyan Plasmodium falciparum.

Pyrimethamine (PM) plus sulfadoxine (SD) is the last remaining affordable drug for treating uncomplicated malaria in Africa. The selective pressure exerted by the slowly eliminated combination PM/SD was compared with that exerted by the more rapidly eliminated combination chlorproguanil/dapsone (CPG/Dap) on Kenyan Plasmodium falciparum. Point mutations were analyzed in dihydrofolate reductase and dihydropteroate synthase and in the genetic diversity of 3 genes in isolates collected before and after CPG/Dap and PM/SD treatments. PM/SD was associated strongly with the disappearance of fully drug-sensitive parasites and with a significant increase in the prevalence of resistant parasites in subsequent parasitemias. However, this was not a characteristic of treatment with CPG/Dap. Moreover, most of the patients who returned with recrudescent infections were in the PM/SD-treated group. The data predict a longer useful therapeutic life for CPG/Dap than for PM/SD, and, thus, CPG/Dap is a preferable alternative for treatment of chloroquine-resistant falciparum malaria in sub-Saharan Africa.

Animals↗
PubMed2001

Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture.

To investigate whether amiodarone increases interleukin-6 (IL-6) production in thyrocytes, human follicles obtained from subtotally thyroidectomized patients with Graves' disease were cultured in serum-free medium supplemented with various concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles gradually formed monolayer cells and secreted triiodothyronine (T3), thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-dependently increased T3 and Tg but not IL-6 levels in the conditioned medium. Amiodarone exerted no significant effect on T3, Tg, or IL-6 concentrations at 0.1-1 microM. In contrast, at 10-20 microM, it decreased T3 and Tg, but increased IL-6 levels, and these changes were accompanied by increased expression of IL-6 mRNA. Amiodarone-induced IL-6 production was inhibited by prednisolone at 10(-7) M. Electron microscopic examination revealed that the thyroid follicles in the suspension culture remained intact at 1 microM, but that cytotoxic effects (decreased microvilli and increased onion-like inclusion bodies) occurred at higher concentrations (10-25 microM). These in vitro findings indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 microM), but exerts cytotoxic effect by inducing the production of a proinflammatory cytokine (IL-6) at higher concentrations. Because amiodarone-induced IL-6 production was inhibited by prednisolone, it is reasonable to administer glucocorticoids to patients with amiodarone-induced destructive thyrotoxicosis (type II).

Amiodarone↗
PubMed1999

High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate.

We have developed a new approach to detect mechanical forces exerted by locomoting fibroblasts on the substrate. Cells were cultured on elastic, collagen-coated polyacrylamide sheets embedded with 0. 2-micrometer fluorescent beads. Forces exerted by the cell cause deformation of the substrate and displacement of the beads. By recording the position of beads during cell locomotion and after cell removal, we discovered that most forces were radially distributed, switching direction in the anterior region. Deformations near the leading edge were strong, transient, and variable in magnitude, consistent with active local contractions, whereas those in the posterior region were weaker, more stable, and more uniform, consistent with passive resistance. Treatment of cells with cytochalasin D or myosin II inhibitors caused relaxation of the forces, suggesting that they are generated primarily via actin-myosin II interactions; treatment with nocodazole caused no immediate effect on forces. Immunofluorescence indicated that the frontal region of strong deformation contained many vinculin plaques but no apparent concentration of actin or myosin II filaments. Strong mechanical forces in the anterior region, generated by locally activated myosin II and transmitted through vinculin-rich structures, likely play a major role in cell locomotion and in mechanical signaling with the surrounding environment.

3T3 Cells↗