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At least 19 recordsLinked to original sources

Characterization of murine bronchoalveolar macrophage respiratory burst: comparison of soluble and particulate stimuli.

Stimulation of the respiratory burst of murine bronchoalveolar macrophages obtained by lung lavage was studied using four different stimuli and different assay conditions. One soluble stimulus, phorbol myristate acetate (PMA), two intracellular particles, zymosan and Blastomyces dermatitidis conida, and one extracellular particle, B. dermatitidis yeast, were incubated with either freshly obtained macrophages in suspension or 2- and 48-hour macrophage monolayers. Suspension cultures were incubated with stimuli for 90 minutes and monolayers for 10 minutes before O2- was assayed. PMA did not elicit O2- production in macrophage suspensions or 2-hour macrophage monolayers, but 48-hour macrophage monolayers exhibited a 13-fold increase above control values (P = .0001). On the other hand, zymosan elicited an increase in O2- production in both suspensions and monolayers, although monolayers incubated for 48 hours produced almost fourfold more O2- than the other systems (P = .025). Opsonization had no effect on the ability of zymosan to elicit respiratory burst. B. dermatitidis conidia resulted in a two- to threefold increase in O2- production in macrophage suspensions and a five- to eightfold increase in 48-hour monolayers, representing significantly less respiratory burst stimulation than with either zymosan or PMA. Similarly, B. dermatitidis yeasts demonstrated similar submaximal stimulation of O2-, 3-4 times that over control values, and again this was less than zymosan and PMA. We conclude that 1) freshly obtained murine bronchoalveolar macrophages do not respond to PMA with an increase in O2- production, but that responsiveness is evident after 48 hours of incubation in monolayers; 2) B. dermatitidis conidia and yeasts do not stimulate respiratory burst activity to the same degree as zymosan or PMA; and 3) opsonization of zymosan is not necessary for stimulation of the murine bronchoalveolar macrophage oxidative burst, confirming previous data that functional complement receptors are not present on these cells.

Animals↗

Interference of sex-related factors in the response of liver cells to experimental mitotic stimuli.

Stimulation of liver cell multiplication was obtained under two different experimental conditions. (1) A single injection of casein solution resulted in (a) an identical synchronized mitotic wave response in 10-day old male and female rats and (b) a significantly lower response in adult male rats compared to females, a difference which was reduced by castration of males at birth but essentially maintained if animals were operated when 10 days old. (2) Partial hepatectomy shortly after puberty resulted in active hepatocyte multiplication occurring 3 hr earlier in females were ovariectomized at birth and significantly reduced when they were spayed at a later age. Hepatocytes of castrated females entered actively into S phase 2 hr later than the sham-operated controls. Unilateral ovariectomy on the other hand indicated that during compensatory and/or hypercompensatory activity of the single ovary there was a maximum difference between the male and female rate of [3H]thymidine uptake in liver nuclei 20 hr after hepatectomy. A further kinetic study (t = 25, 30,40, 65, 90 hr) indicated no significant sex-related difference in the number of S phases per 10,000 cells. The DNA content of regenerating versus control livers was comparable in both sexes at t = 22 and 90 hr but higher in females at t = 40 and 65 hr. A possible early postnatal interference of certain hormonal mechanisms in the receptivity to mitotic stimuli is postulated and discussed.

Animals↗

Arachidonic acid can induce leukotriene C4 formation by purified human eosinophils in the absence of other stimuli.

Stimulation of purified human eosinophils with 50 microM arachidonic acid leads to the production of leukotriene C4, 15-hydroxy-eicosatetraenoic acid and 15-series leukotrienes. The ratio of the amounts of leukotriene C4 and 15-lipoxygenase products was found to be strongly dependent on the arachidonic acid concentration, being relatively large at low arachidonic acid concentrations and very small at high arachidonic acid concentrations. In the presence of 1 microM platelet-activating factor a significant elevation of leukotriene C4 formation is observed, whereas the formation of 15-lipoxygenase products remains unaltered. As arachidonic acid was found to be capable of inducing a fast, transient rise in the cytosolic free Ca2+ concentration, this explains at least partly its ability to induce the Ca2+-dependent formation of leukotriene C4.

Arachidonic Acid↗

Response threshold to aversive stimuli in stimulated early protein-malnourished rats.

Two animal models of pain were used to study the effects of short-term protein malnutrition and environmental stimulation on the response threshold to aversive stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age while the mothers of the other half (controls) were well nourished, receiving 16% protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the animals in the malnourished and control groups were maintained under stimulating conditions, including a 3-min daily handling from 0 to 70 days and an enriched living cage after weaning. The other half was reared in a standard living cage. At 70 days, independent groups of rats were exposed to the shock threshold or to the tail-flick test. The results showed lower body and brain weights in malnourished rats when compared with controls at weaning and testing. In the shock threshold test the malnourished animals were more sensitive to electric shock and environmental stimulation increased the shock threshold. No differences due to diet or environmental stimulation were found in the tail-flick procedure. These results demonstrate that protein malnutrition imposed only during the lactation period is efficient in inducing hyperreactivity to electric shock and that environmental stimulation attenuates the differences in shock threshold produced by protein malnutrition.

Animals↗

Resolution of single deviant intervals in periodic stimuli by auditory cortex neurons: comparison of intracochlear electric pulse and acoustic click stimulation.

Responses of neurons in the primary auditory cortex were compared in gerbils receiving intracochlear electric or acoustic stimulation. Stimuli were trains of periodic electric pulses or of acoustic clicks. Interspersed between intervals of equal length were single intervals which were longer, by some Delta t. The Delta t and the repetition rate of these prolonged intervals were varied. The degree of synchronization of spikes to the regular occurrences of prolonged intervals was quantified. While thresholds for synchronized responses to Delta t (at Delta t repetition rates of 4--6 Hz) were about a hundredfold higher for electric (about 5--10 ms) than for acoustic stimulation (about 30 s), Delta t repetition rate response functions were similar for both types of stimulation. The results suggest the feasibility of coding brief acoustic transients by prolonged intervals in electric pulse trains with high pulse repetition rates, which could be another useful strategy for cochlear implants.

Acoustic Stimulation↗

Induction of lytic pathways in T cell clones derived from wild-type or protein tyrosine kinase Fyn mutant mice.

The OVA-reactive CD4+ Th1 clones and alloreactive CD8+ clones derived from wild-type or fyn-/- mice serve as model systems which have allowed us to investigate several aspects of the molecular events associated with T cell-mediated cytotoxicity, including 1) the differential utilization of two distinct cytolytic pathways by CD4+ Th1 clones and CD8+ CTL, 2) a comparison of the pathways of lysis induced by stimulation of the TCR or by alternative stimuli, 3) the requirement of Fyn for derivation of antigen-specific T-cell clones having properties of CD4+ Th1 and CD8+ CTL cells 4) the differential requirement of Fyn in the induction of responses by TCR and the alternative stimuli. Stimulation through the TCR, either by APC bearing relevant antigen or by immobilized anti-CD3 mAb, resulted in comparable levels of target cell lysis by clones from both wild-type and fyn-/- mice. These clones also utilize the Fas pathway to lyse target cells. Thus, Fyn does not appear to be required for expression of the Fas pathway when triggered through the TCR. In contrast, lysis of target cells by T-cell clones lacking Fyn was deficient when stimulated through Thy-1 or Ly-6C (using mAb) or with Con A or phorbol ester as compared to clones derived from wild-type mice. The basis for the defect in response to stimulation through the GPI-linked molecules appears to be a signaling defect which affects all of the functional responses we measured, while the defect in response to Con A stimulation appears to affect lysis but not lymphokine production. Thus, Fyn expression is selectively required for efficient activation of the Fas pathway of lysis through Thy-1, Ly-6C, and by Con A or phorbol ester in these T-cell clones. CD8+ clones derived from fyn-/- mutant mice, like clones derived from wild-type mice, display antigen-specific lysis, and appear to express perforin message and perforin protein. A Ca(++)-dependent (presumably perforin/exocytosis) component and Fas component of lysis was detected in CD8+ clones derived from fyn-/- mutant mice. Thus, Fyn is not required for expression of these components of antigen specific lysis by CD8+ alloreactive CTL clones. It appears that CD8+ clones that use multiple lytic mechanisms may selectively employ the perforin or Fas-based pathway depending on properties of the target cell or stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Inhibition of the spinal transmission of nociceptive information by supraspinal stimulation in the cat.

In cats anaesthetized with alpha-chloralose or sodium pentobarbitone a study was made of the effects of supraspinal electrical stimulation on the excitation of dorsal horn neurones by noxious and non-noxious cutaneous stimuli. Stimulation near the dorsal raphe of the midbrain non-selectively reduced the responses of neurones to both noxious and non-noxious stimuli. Intravenous naloxone (0.3-0.6 mg/kg) had no effect on this inhibition. Electrical stimulation near the medullary raphe selectively reduced the excitation of dorsal horn neurones by noxious cutaneous stimuli. Excitation of neurones by deflection of hairs was unaffected. The inhibition of nociceptive responses outlasted the period of raphe stimulation by up to 6 min. Intravenous naloxone (0.6-1.0 mg/kg) also failed to affect this selective inhibition.

Animals↗

Physiologic effects of nucleus basalis magnocellularis stimulation on rat barrel cortex neurons.

Cholinergic neurons in the nucleus basalis magnocellularis (NBM) project to the cerebral cortex and are thought to play an important role in learning and memory, and other cognitive functions. In the present study, we examined the effects of NBM stimulation on the response properties of individual cortical neurons in layer V of the rat somatosensory cortex. Seventy-three neurons were studied before and after a brief electrical stimulation of NBM. Transient changes in spontaneous activity were observed in 60% of the cells, and in most cases this background activity decreased. Recordings lasting more than 1 h stimulation were obtained from 56 cells. Because some NBM stimulation-induced effects lasted several hours, neurons were evaluated in two groups, NBM1 and NBM2. NBM1 neurons were those exposed to either the first NBM stimulation of the day or an NBM restimulation following a more than 5 h stimulation-free period. Neurons exposed to NBM restimulation following a stimulation free interval of less than 5 h were classified as NBM2. Sixty-nine percent of the 32 NBM1 neurons displayed marked decreases in spontaneous activity and/or increases in the response evoked by deflecting a contralateral facial vibrissa. NBM1 stimulation caused some units to respond to previously minimally effective whisker stimuli. Stimulation effects often lasted several hours. By contrast, long-lasting changes were observed in only 25% of the 24 NBM2 neurons, and the only consistent effect was on spontaneous, not stimulus-evoked, activity. Systemic injection of atropine blocked NBM stimulation-induced changes in spontaneous and stimulus-evoked activities. Control neurons, studied without NBM stimulation, failed to display consistent alterations in their response properties during the course of 1 h or more. Results demonstrate that NBM activation produces long-lasting, cholinergically mediated alterations in the response properties of somatosensory cortical neurons. Effects were complex, being influenced by factors such as the time interval between successive stimulations during an experiment. The complexity of these NBM mediated effects should be considered when designing therapies for neurodegenerative disorders characterized by loss of NBM neurons.

Animals↗

Responses of rat lateral hypothalamic neurons to periaqueductal gray stimulation and nociceptive stimuli.

The effects of dorsal periaqueductal gray (D-PAG) stimulation and noxious stimuli on neural activity in the lateral hypothalamic area (LHA) were investigated in 56 adult male anesthetized rats. Strong tail pinch was used as noxious stimulation. We examined 234 extracellular and 75 intracellular recordings of LHA responses to electrical stimulation of D-PAG. To determine neurotransmitter candidates, the effects of the opioid agonist, morphine, and its antagonist, naloxone were investigated by systemic administration and microelectrophoresis. Of 234 spontaneously firing LHA neurons, 70 (30%) were inhibited by D-PAG stimulation. Of these 70 neurons, 26/40 tested (65%) were glucose-sensitive, 16/19 (84%) were inhibited by morphine and 12/18 (67%) were inhibited by tail pinch. Glucose-sensitive neurons were selectively inhibited by morphine and tail pinch. Naloxone attenuated inhibitory responses to D-PAG stimulation, tail pinch and electrophoretic morphine. From intracellular recordings these polysynaptic inhibitory responses to D-PAG stimulation were considered to be inhibitory postsynaptic potentials (IPSPs) with 6.1 +/- 3.2 ms (mean +/- S.D.) latency and reversal membrane potential of about -78 mV. Since LHA glucose-sensitive neurons receive, selectively, both inhibitory opioid inputs from the D-PAG and inhibitory inputs through noxious stimulation, we suggest that D-PAG might be an intermediate site for transmission of noxious stimuli to the LHA.

Animals↗

Structural and functional organization of a diencephalic sensory-motor interface in the gymnotiform fish, Eigenmannia.

The diencephalic nucleus electrosensorius (nE) of gymnotiform fish comprises a series of finely tuned neuronal filters for control of the jamming avoidance response (JAR) and probably other electromotor tasks as well. The nE receives electrosensory input from the dorsal torus semicircularis (TSd) and octavolateral input from the ventral torus (TSv). The nE, in turn, projects to various hypothalamic and thalamic nuclei, including the prepacemaker nucleus (PPn), which can modulate the frequency of electric organ discharges (EODs) via its unique input to the medullary pacemaker nucleus. Four subdivisions of the nE can now be recognized: 1) The beat-related area (nEb)--a rostral cluster of tightly packed cells which receives TSd input and projects to the inferior lobe, anterior tuberal nucleus, anterior thalamic nucleus, central posterior thalamic nucleus, and PPn. The nEb contains neurons responsive to beat patterns caused by jamming stimuli. Stimulation of the nEb with L-glutamate, however, fails to induce any EOD-frequency shift. 2) The area causing EOD-frequency rises (nE increases)--a horizontal band of cells at the dorsal aspect of the caudal nE which receives TSd input and projects to the PPn and vicinity and to the cerebellum; nE increases stimulation induces slow EOD-frequency rises characteristic of the JAR. Responses of these cells to jamming stimuli are not yet known. 3) The area causing EOD-frequency falls (nE decreases)--a horizontal band of cells at the ventral aspect of the caudal nE which receives TSd input and projects only to the PPn and vicinity; nE decreases stimulation induces slow EOD-frequency falls characteristic of the JAR. The responses of these cells to jamming stimuli are not yet known. 4) The acousticolateral region (nEar)--a complex medial region of the nE which receives input predominantly from the ventral torus and projects to the inferior lobe, anterior tuberal nucleus, central posterior thalamic nucleus, PPn, and cerebellum; the sensory and motor properties of this region are not known in detail, although auditory and mechanosensory responses have been recorded here. Projections to the PPn and its vicinity suggest direct control of electromotor behaviors by the nE, whereas thalamic and hypothalamic projections may provide a substrate for electrosensory influences on neuroendocrine and motivational control centers. The optic tectum projects strongly to the pretectum and various other diencephalic nuclei in the vicinity of the nE, but it does not innervate the nE itself. Accordingly, ablation of the tectum does not affect the performance of the JAR.

Animals↗

The corneal reflex and the R2 component of the blink reflex.

A reflex contraction of the human orbicularis oculi muscles can be evoked by stimulation of either the supraorbital region ("blink reflex") or the cornea ("corneal reflex"). We found that the latency of the corneal reflex was longer, and the duration was longer than the R2 component of the blink reflex. The absolute refractory period of the R2 component of the blink reflex was longer after supraorbital than after corneal conditioning stimulation. When the R2 component of the blink reflex was habituated by repetitive stimuli, stimulation of the cornea still evoked a reflex, but supraorbital stimulation produced only a depressed R2 response. These findings suggest that the two reflexes do not have identical neural connections.

Adult↗

Auditory and visual evoked potentials to irrelevant stimuli during conditioning to a visual stimulus.

Amplitude changes of evoked responses to irrelevant auditory (click) and visual (optic tract stimulation) stimuli were examined during appetitive conditioning to a flashing light. Four female cats, with chronically implanted electrodes along the visual and auditory pathways, were conditioned with pairings of a flashing light and food reinforcement. The results showed that, as conditioning progressed, the auditory evoked potentials were attenuated while the visual evoked potentials did not change significantly. The data seem to indicate possible differences in the neural processing of irrelevant information.

Animals↗

Overexpression of c-Fos is sufficient to stimulate tyrosine hydroxylase (TH) gene transcription in rat pheochromocytoma PC18 cells.

The AP1 site within the tyrosine hydroxylase gene proximal promoter is essential for the response of the gene to numerous stimuli. Stimulation of this gene is often associated with induction of the AP1 transcription factor, c-Fos. However, many stimuli activate or induce multiple transcription factors that interact with this AP1 site or other sites within the gene's proximal promoter. Hence, it remains unclear whether c-Fos induction by itself is sufficient to stimulate the tyrosine hydroxylase gene. In this study we produce rat pheochromocytoma PC18 cells that overexpress c-Fos under control of the tet-inducible system. We demonstrate that induction of c-Fos leads to dramatic stimulation of tyrosine hydroxylase gene transcription rate measured using nuclear run-on assays. This stimulation is closely associated quantitatively with the induction of c-Fos and does not apparently require phosphorylation of c-Fos. The response is partially dependent on the AP1 site within the tyrosine hydroxylase proximal promoter. However, the response of the proximal promoter to c-Fos induction is relatively small compared with that of the endogenous gene. Consequently, our results suggest that c-Fos exerts its influence on the tyrosine hydroxylase gene via multiple mechanisms that are dependent and independent of the proximal promoter AP1 site.

5' Flanking Region↗

[Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells.

Cardiac hypertrophy is a process that occurs in response to various mechanical or hormonal stimuli. Stimulation of the renin-angiotensin system is involved in the process of cardiac hypertrophy through mechanisms related to increased peripheral vascular resistance and increased cardiac afterload. In this study we determined whether [Sar1]angiotensin II (ANG II) directly stimulated protein synthesis and cell growth in embryonic chick myocytes in cell culture. Eighteen-day-old embryonic chick myocytes in subconfluent cell culture, incubated in a chemically defined serum-free media, showed a significant increase in total protein content, 18.5, 26.2, and 22.2%, respectively, when exposed to [Sar1]ANG II (1 microM/day) for 5, 7, and 9 days, respectively. The increase in total protein resulted in part from an increase in the fractional protein synthesis rate of 21.7, 16.5, and 14.9% at 5, 7, and 9 days, respectively. Total DNA and RNA levels did not change significantly following a 4-day exposure to [Sar1]ANG II in subconfluent culture. The relative rate of protein synthesis, determined by pulse labeling for 3 h with [3H]phenylalanine, showed increases of 23.4, 22.9, and 17.8% over control after 4, 5, and 6 days of exposure to [Sar1]ANG II. The incorporation of [3H]phenylalanine was blocked by the specific ANG II-receptor antagonist [Sar1,Ile8]ANG II. The data demonstrate a receptor-mediated increase in the rate of protein synthesis in cultured chick myocytes in response to [Sar1]ANG II, with a resultant increase in total cellular protein. This angiotensin peptide appears to directly stimulate protein synthesis in cultured embryonic chick myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Periaqueductal grey stimulation: an association between selective inhibition of dorsal horn neurones and changes in peripheral circulation.

In barbiturate-anaesthetized and paralysed cats, dorsal horn neurones were studied during electrical stimulation of the periaqueductal grey matter (PAG) and the midbrain ventral tegmentum (VT). Responses to impulses in unmyelinated primary afferents were selectively inhibited by stimulation in the PAG, whereas stimulation in the VT non-selectively reduced both these responses and those to innocuous cutaneous stimuli. Stimulation in the PAG but not the VT produced changes in peripheral circulation. This was observed as a rise in the levels of carbon dioxide in expired air, a rise in muscle temperature in the hind limb and a fall in skin temperature of the pinna or glabrous skin. The combination of suppression of spinal transmission of impulses related to pain and an increase in perfusion of muscles may be a mechanism appropriate to coping with a potentially injurious environment.

Animals↗

[Effect of hippocampal stimulation on the feeding behavior of cats].

Influence of electrical stimulation (100 cps., 1.0 ms) of medial parts of dorsal and ventral hippocampus (field CA1), and the lateral parts of dorsal and posterior hippocampus (field CA3) on general behaviour, elaboration of instrumental and manifestation of delayed reactions was studied in chronic experiments on cats. Stimulation of medial parts of dorsal and ventral hippocampus elicited a reaction of orienting reflex type to natural stimuli. Stimulation of lateral parts of dorsal and posterior hippocampus evoked arrest reactions. Medial and lateral parts of hippocampus produced different influences on elaboration of conditioned reflexes. In the first case elaboration was possible, but developed slower, while in the second case the ability to learn during stimulation was completely lost due to development of arrest reaction. Stimulation of different parts of the hippocampus disturbed delayed reactions, reducing the number of correct responses.

Animals↗

Prostaglandins in adrenergic transmission of isolated perfused rat pancreas.

In the isolated, perfused rat pancreas, prostaglandins (PGs) E1 and E2 1-5 ng/ml, reduced the vasoconstrictor responses to periarterial nerve stimulation and variably affected those to injected norepinephrine. Prostaglandin F2alpha had no consistent effect on the vasoconstrictor responses to both adrenergic stimuli. Stimulation of adrenergic nerves or administration of norepinephrine released a PGE-like substance from the perfused pancreas which was abolished by inhibitors of PG synthesis, acetylsalicylic acid, indomethacin, meclofenamate, and eicosa-5,8,11,14-tetraynoic acid. The latter three agents did not potentiate, but rather reduced the vasoconstrictor responses to both adrenergic stimuli. Arachidonic acid that was converted by the pancreas into PGE2 and PGF2alpha inhibited the vasoconstrictor responses to adrenergic stimuli. The latter effect of arachidonic acid was not altered by the simultaneous infusion of PG synthetase inhibitors. Although these results, which could be attributed to a direct effect of inhibitors of PG synthesis and arachidonic acid on adrenergic neuroeffector junction, fail to establish the role of endogenous PGs in modulating adrenergic responses in rat pancreatic vessels, they emphasize the differences in the effect of PGE1 and PGE2 on adrenergic responses in various vascular beds of the rat.

5,8,11,14-Eicosatetraynoic Acid↗

Influence of somatosensory input on paroxysmal activity in benign rolandic epilepsy with 'extreme somatosensory evoked potentials'.

We studied six patients suffering from benign rolandic epilepsy of childhood with central temporal spikes who presented so-called 'extreme somatosensory evoked potentials (SEPs)' following peripheral somatosensory stimulation. Stimuli were delivered to the fingers of one hand using both a triggered tendon hammer and low-intensity electrical stimulation. The electrical stimulation was delivered in sequences in different conditions (i.e. random order, 1, 3 and 10 Hz). Both tapping and electrical stimulation produced scalp evoked potentials in all subjects, characterized by a spike followed by a slow wave, similar in morphology and scalp distribution to the spontaneously occurring spikes. This paroxysmal activity was sensitive to stimulus rate; the number of evoked spikes was inversely related to the frequency of stimulation, being maximal at 1 Hz and disappearing at high frequencies (10 Hz). Spontaneous spikes disappeared during high-frequency stimulation but were present during low-frequency stimulation. Averaged SEPs at 3-Hz stimulation showed a late high-amplitude component, identical in morphology and distribution to the single evoked spike. We therefore conclude that, in these subjects, the so-called 'extreme SEPs' are evoked spikes and that evoked and spontaneous spikes share common cortical sensorimotor generators. The evidence that these generators can be influenced by afferent input provides important information regarding the functional mechanisms involved in modulating cortical excitability in benign rolandic epilepsy. Moreover, we suggest that peripheral electrical stimulation can be used as an additional activation test in this kind of epilepsy.

Age of Onset↗