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At least 811 records · Page 45Linked to original sources

Release of leukotrienes C (LTC) and D (LTD) from inflammatory macrophages during phagocytosis of zymosan and bacteria.

Release of slow-reacting substance (SRS) was obtained from resident mouse peritoneal macrophages (R-M phi) upon stimulation with phagocytic stimuli (zymosan, bacteria). The release of SRS from thioglycollate elicited M phi was impaired, whereas that from BCG-elicited M phi was quantitatively unaffected. However, using a high pressure liquid chromatography separation procedure, qualitative variations between SRS released from R-M phi and BCG-M phi were observed. In both cases, LTC was the major component released from M phi, but greater amounts of LTD were released from BCG-M phi than from R-M phi. These data indicate that local environment alters leukotriene generation by M phi.

Animals↗

[Metronome therapy in patients with Parkinson disease].

We studied 10 patients with Parkinson's disease and 12 patients with Parkinson-plus-syndrome, trying to improve patients' gait by application of various external rhythmic stimuli, including metronome stimulation (96 beats per minute = middle andante). The test course of the patients was 4 x 10 meters and 3 U-turns. The patients' gait quality under stimulation was compared with their free walk (velocity, number of steps, number of freezing episodes). Metronome stimulation significantly reduced the time and number of steps needed for the test course and also diminished the number of freezing episodes. March music stimulation was less effective and tactile stimulation (rhythmically tapping on the patient's shoulder) even produced negative results. The positive effect of metronome stimulation was also found, when the tests were not performed inside the hospital building, but outside in the hospital parc. Metronome stimulation was comparably effective in both patient sub-groups examined in this study (M. Parkinson, Parkinson-plus-syndrome) and seems to be an important additional help in the treatment of these patients. Electronical metronomes are not expensive, easy in handling, and portable. A theoretical explanation of metronome stimulation effectivity in patients with Parkinson's disease still needs to be elucidated.

Acoustic Stimulation↗

High interleukin 12 and low interleukin 10 production after in vitro stimulation detected in sepsis survivors.

OBJECTIVE: To evaluate viability of isolated peripheral blood mononuclear cells (PBMC) and production of cytokines in vitro after stimulation as prognostic factors for survival in sepsis patients. DESIGN: Prospective study of the biological response of PBMC in the onset of severe sepsis. SETTING: Research laboratory of molecular biology and immunology and university hospital ICU, Faculty of Medicine, Trakia University. PATIENTS: Twenty-three patients meeting the criteria for severe sepsis, and 14 control subjects. INTERVENTIONS: Isolated PBMC were stimulated in vitro with: C3-binding glycoprotein (C3bgp; 30 microg), lipopolysaccharide (30 microg), phytohemagglutinin (20 microg), pokeweed mitogen (30 microg), and dexamethasone (500 microg). MEASUREMENTS AND RESULTS: We measured the levels of interleukins (IL) 6, 10, and 12 in culture supernatants. Stimulation with C3bgp and phytohemagglutinin led to significantly lower PBMC secretion of IL-6 in nonsurvivors than in survivors and healthy donors. Stimulation with C3bgp, lipopolysaccharide, and pokeweed mitogen considerably reduced IL-12 production in nonsurvivors. Stimulation with lipopolysaccharide and pokeweed mitogen caused immune cells in nonsurvivors to produce higher levels of IL-10 than in survivors. Survival of PBMC reduced viability for nonsurvivors' PBMC, both spontaneously and as induced by lipopolysaccharide or pokeweed mitogen. CONCLUSIONS: The viability of PBMC at the onset of sepsis and enhanced production of IL-12 and diminished production of IL-10 after stimulation with all stimuli used may be a favorable prognostic factor in sepsis.

Adolescent↗

Perceptual requirements for fast manual responses.

The on-line visual control of human movements can be exceptionally fast. Whether it is fast depends on the kind of visual information that is involved. In the present study we examine whether fast on-line control is specific to the magnocellular visual pathway. Fast manual responses become evident when an ongoing movement has to be adjusted, for instance because the target is displaced. We examined whether the response to such perturbations is faster for stimuli that only activate the magnocellular pathway than for equally conspicuous stimuli that only activate the parvocellular pathway. The response was indeed about 35 ms faster for stimuli that activate the magnocellular pathway. However, we argue that the slower response to stimuli that only stimulate the parvocellular pathway is due to the properties of the neurones involved and the less direct connection to the motor areas, rather than to fast reactions being driven exclusively by magnocellular input.

Hand↗

Cyclic nucleotides and growth regulation of the mandibular condylar cartilage of the rat in vitro.

By exogenous interference in the intracellular level of cAMP and cGMP during growth in vitro without and with compression, an indication was obtained for the mediatorial involvement of these cyclic nucleotides in the major growth-processes in the mandibular condylar cartilage of 4-day-old rats. Raising the intracellular level of cAMP reduced proliferative activity in the prechondroblast zone, did not affect matrix synthesis by the functional chondroblasts and stimulated the process of hypertrophy. Intracellular elevation of cGMP had an antagonistic effect; it stimulated proliferation as well as matrix synthesis, but had no effect on hypertrophy. In this specific type of cartilage, cGMP can be considered as a major secondary intracellular messenger for proliferation-stimulating continuous biomechanical stimuli.

Animals↗

Measurement of tooth hypersensitivity and oral factors involved in its development.

The various methods of measurement of dentinal hypersensitivity are based upon the types of stimuli used to elicit a pain response in teeth, which include thermal, tactile, evaporative, electrical and osmotic. Pulpal inflammation in its early stages reduce the threshold of pain response to these stimuli but electrical stimulation may make it possible to assess the possible contribution of such inflammation to sensitivity determinations. Although the magnitude of each stimulus is quantifiable, patient response is subjective, which necessarily makes measurements of dentinal sensitivity semisubjective. Various methods of testing dentinal sensitivity are discussed, along with their advantages and disadvantages. The teeth most suited for measurement in clinical studies are the canines and premolars. This is because approx. 80% of the sensitivity lesions are associated with these teeth, which have similar thicknesses of root dentine. Data from several studies involving the same subjects indicate that individual measurements readily return to baseline and that the commonly seen placebo effect is probably due to some as yet unidentified factor in desensitizing formulations. Possible roles of salivary and plaque environmental factors in the development of dentinal sensitivity are discussed, as well as methods for their measurement.

Beverages↗

Inhibition of the release of prostaglandins, leukotrienes and lysosomal acid hydrolases from macrophages by selective inhibitors of lecithin biosynthesis.

The release of the inflammatory mediators, prostaglandins (PGs), leukotrienes (LT) and lysosomal acid hydrolases (LAH), by macrophages is stimulated by endocytic stimuli such as zymosan. This process can be interfered with by specific inhibitors of phosphatidylcholine (PC) biosynthesis. The diphenylsulfone dapsone and three analogs selectively inhibited [14C]choline incorporation into PC but had varied effects on inhibition of mediator release by macrophages. Dapsone inhibited the release of PGs, LT and LAH, whereas the three closely related structural analogs inhibited LAH release only, with little or no effect on PG production.

Animals↗

Use and misuse of electroconvulsive treatment.

For the continued availability of electroconvulsive therapy (ECT) in clinical practice on equal footing with other treatments, and without judicial interference, the following points are essential: ECT should be used or not used on the basis of scientific evidence and not because of public opinion or antipsychiatric propaganda. There should be no hesitation to use ECT in conditions where its omission would mean prolonged suffering, risk of suicide, or death from other causes (deep melancholic syndromes, acute lethal catatonia, psychogenic confusion). ECT should not be used where the effect is short-lived or must be paid at the price of an organic syndrome (schizophrenia, paranoid states, organic confusions). Efficiency should be optimal (oxygen, superficial narcosis, absence of benzodiazepines, generalized tonic-clonic seizures of at least 30-sec duration, maintenance treatment with antidepressive drugs). Safety should be optimal, not only for life but also for cerebral functioning (anesthesiological management, unilateral nondominant stimulation, pulse wave stimuli, appropriate number of treatments, not too closely spaced). The mechanism of action should be the object of further investigation. Such research will open possibilities for finding drugs that can compete with ECT.

Bipolar Disorder↗

Opiate vs non-opiate footshock induced analgesia (FSIA): descending and intraspinal components.

Opiate and non-opiate footshock induced analgesia (FSIA) can be differentially elicited dependent upon the body region shocked. As measured by the spinally-mediated tail flick test, hind paw shock produces non-opiate analgesia where front paw shock produces opiate analgesia. The present series of experiments utilized cord lesions and transections to identify descending and intraspinal pathways mediating front paw and hind paw FSIA. The results of these studies indicate that front paw shock leads to activation of supraspinal sites which mediate analgesia via descending pathways lying solely within the dorsolateral funiculus (DLF) of the spinal cord; direct intraspinal pathways are not involved. Hind paw FSIA is also mediated by a descending DLF pathway but is unlike front paw FSIA in that it involves intraspinal pathways as well. This work provides further parallels between the analgesias produced by morphine, electrical brain stimulation and environmental stimuli.

Analgesia↗

Preconditioning and excitability of the human orbicularis oculi reflex as a function of state.

Reflex excitability and unstimulated activity of orbicularis oculi were found to vary as a function of state but the effects of weak conditioning stimuli, preceding reflex stimulation by 30--210 msec, were independent of state. Electromyographic activity was recorded from 23 young adults: 12 subjects with eyes closed during quiet wakefulness, 3 subjects during all-night sleep, 8 subjects during an afternoon nap. Stimulation with a 50 msec, 105 dB(A) white noise burst elicited a reflex response in 92% of waking trials and 87% of trials during REM sleep, but responses occurred in only 54% of trials during NREM sleep. Further, response latency was longer and magnitude less during the NREM state. Despite the differences in reflex excitability associated with state, state did not affect the modifications of reflex activity produced by a 20 msec, 70 dB(A) conditioning tone. At all lead intervals, reflex magnitude was reduced by the weak prestimulation even though, at the shortest interval, reflex activity was initiated more rapidly. The discordant changes in reflex size and latency have been seen in previous waking studies and appear to be mediated by different mechanisms. The persistence of both effects during sleep suggests that neither effect depends on high-level central processes.

Acoustic Stimulation↗

Rod- and cone-mediated visual function in multiple sclerosis.

Visual thresholds and perceptual latencies were determined in patients with multiple sclerosis (MS) and in normal control subjects. Measurements were made under light- and dark-adapted conditions, with stimuli chosen to stimulate rod and cone receptors selectively. More abnormalities in perceptual latency and luminance threshold were recorded in the light-adapted condition than in the dark-adapted condition, but this result was not specific to the rod or cone systems. Possible underlying pathophysiological processes are discussed, and it is suggested that reduced conduction velocity in the demyelinated visual pathway is the most likely explanation of the observed perceptual delays and that there is no evident retinal contribution.

Adult↗

A comparison of stereo and vernier acuity within spatial channels as a function of distance from fixation.

We have used DOG stimuli to selectively stimulate size tuned channels within the visual system in order to investigate the relationship between stereo and vernier acuity. We measured these acuities as a function of spatial frequency, retinal eccentricity and distance from the fixation point in depth. Both hyperacuities are poorer with low spatial frequencies but vernier was effected to a smaller extent. Vernier acuity deteriorated to a much greater degree than stereo acuity as retinal eccentricity increased up to 40 arc min. Stereo acuity was more dependent upon distance from the fixation point in depth than would be expected from the dependence of vernier acuity on retinal eccentricity. We conclude that there must be different limiting factors for the two hyperacuity tasks.

Depth Perception↗

Neurones with strong inhibitory S-cone inputs in the macaque lateral geniculate nucleus.

Neurons with strong inhibitory short-wavelength sensitive cone (S-cone) inputs have been identified in the macaque geniculate using a tritanopic confusion line test, i.e. by stimulation with equiluminous stimuli which leave excitations of long- and middle-wavelength sensitive cones (L- and M-cones) constant while differentially exciting S-cones. Mathematical simulation of the responses of these cells, using known spectral sensitivities of the cone receptors, demonstrates that they receive excitation from M-cones, inhibition from S-cones, and little or no inhibition from L-cones. Excitatory and inhibitory pools are largely spatially coextensive.

Animals↗

Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells.

Nonpancreatic secretory phospholipase A2 (sPLA2) displays proinflammatory properties; however, its physiological substrate is not identified. Although inactive toward intact cells, sPLA2 hydrolyzed phospholipids in membrane microvesicles shed from Ca(2+)-loaded erythrocytes as well as from platelets and from whole blood cells challenged with inflammatory stimuli. sPLA2 was stimulated upon degradation of sphingomyelin (SPH) and produced lysophosphatidic acid (LPA), which induced platelet aggregation. Finally, lysophospholipid-containing vesicles and sPLA2 were detected in inflammatory fluids in relative proportions identical to those used in vitro. We conclude that upon loss of phospholipid asymmetry, cell-derived microvesicles provide a preferential substrate for sPLA2. SPH hydrolysis, which is provoked by various cytokines, regulates sPLA2 activity, and the novel lipid mediator LPA can be generated by this pathway.

Animals↗

Recognition of a granulocyte-specific membrane protein by monoclonal antibodies.

Using membranes isolated from leukemic myeloblasts as immunogen, two granulocyte specific monoclonal antibodies 38D2 and 41D2 were developed. The antibodies are positive in membrane immunofluorescence with granulocytes and bands; they give no reaction with monocytes, platelets, leukemic myeloblasts, lymphoblasts, myeloid cell lines, and immature myeloid cells from bone marrow. Both monoclonal antibodies precipitate the same membrane glycoprotein (MW: 70-78 kd, pI: 6-7), which corresponds to a membrane glycoprotein characteristic for granulocytes, as concluded from two-dimensional polyacrylamide gelelectrophoresis patterns obtained from surface labelled myeloid cells. The monoclonal antibodies did not influence the granulocyte functions tested: phagocytosis of opsonized bacteria, chemiluminiscence after stimulation with various stimuli, and chemotaxis.

Antibodies, Monoclonal↗

Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model.

Previous work in this laboratory has indicated that the transplantation of adrenal medullary tissue into the subarachnoid space of the rat spinal cord can reduce pain sensitivity to acute noxious stimuli, particularly following stimulation by nicotine. This most likely results from the stimulated release of opioid peptides and catecholamines from the transplanted chromaffin cells. However, chronic pain models may more closely resemble human clinical pain, and the arthritic rat model has been used for screening potential therapeutic strategies. The purpose of the present study was to assess the potential for adrenal medullary tissue implanted into the spinal subarachnoid space to alleviate chronic pain. Adrenal medullary tissue was implanted into adjuvant-induced arthritic rats, and changes in body weight and vocalization responses were monitored over the 10 week course of the disease. Results indicate that the severe weight reduction normally associated with this inflammatory arthritis was attenuated by adrenal medullary, but not control, implants. In addition, vocalizations were reduced in animals implanted with adrenal medullary, but not control tissue following nicotine stimulation. This reduction was blocked by the opiate antagonist, naloxone, and partially attenuated by the alpha-adrenergic antagonist, phentolamine. Together, these results suggest that the transplantation of adrenal medullary tissue into the subarachnoid space of the spinal cord may provide a local source of opioid peptides and catecholamines for the reduction of chronic pain.

Adrenal Medulla↗

Patterns of 2-deoxyglucose uptake reflect the neural processing of lordosis-inducing somatosensory stimuli in hamsters.

Semi-quantitative [14C]2-deoxyglucose (2DG) autoradiography was used to map the neural responses of female hamsters to lordosis-inducing flank stimuli. Specifically, manual stimulation of one flank was used to maintain estrous females in lordosis for 20 min after an IV injection of 200 muCi/kg of 2DG. Hemispheric differences in 2DG uptake then were sought in brain nuclei implicated in the programming of lordosis, or in the mediation of somatosensory or hormonal influences on this response. The responses to lateralized flank stimulation included reliable contralateral elevations in 2DG uptake in the ventral posterior lateral nucleus of the thalamus (VPL), the dorsal mesencephalic central gray (dCG), and the tectum. Elevated activity on the part of the VPL may not be crucial for lordosis. However, the effects of flank stimulation on 2DG uptake by the dCG and tectum confirm and extend much previous evidence implicating the dorsal midbrain in the mediation of tactile and hormonal effects on sexual responses. For example, these results suggest that somatosensory influences on hamster lordosis are mediated by both the dCG and tectum. In addition, they suggest that these influences are strongly lateralized until at least this stage of sensory processing, leaving for some subsequent element of neural circuitry the task of translating these lateralized inputs into the bilaterally symmetric outputs ultimately required to program the normal, bilaterally symmetric, lordosis response.

Animals↗

Phosphorylation of rap1B by protein kinase A is not involved in platelet inhibition by cyclic AMP.

The functional consequence of cyclic AMP-dependent phosphorylation of rap1B for stimulus-induced platelet activation is not known. Platelets were pretreated with the stable prostacyclin-analogue iloprost and resuspended in plasma without iloprost. Western blot analysis showed that rap1B was completely converted into its phosphorylated form in the iloprost-pretreated platelets. Surprisingly, the platelets that contained phosphorylated rap1B were found to respond fully to activation by a wide variety of stimuli: aggregation upon stimulation by collagen, phorbol ester, vasopressin, ADP, epinephrine, and ATP-secretion from dense granules induced by collagen, thrombin-receptor activating peptide, vasopressin and phorbol ester were unchanged as compared to control. The results indicate that cyclic AMP-dependent phosphorylation of rap1B does not play a role in the inhibition of the various signal transduction pathways that lead to platelet aggregation and dense granule secretion.

Adenosine Diphosphate↗