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At least 73 records · Page 4Linked to original sources

PubMed2004

Rituximab, anti-CD20, induces in vivo cytokine release but does not impair ex vivo T-cell responses.

Pre-formed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong transplant waiting time. We hypothesized that rituximab (RIT) could reduce PRA via B-cell depletion. As part of a Phase I study of single RIT dose, we studied in vivo and ex vivo effects on T-cell immune responses. Nine subjects (n = 3) were treated at 50, 150, and 375 mg/m(2). Serum interleukin-1alpha (IL-1alpha), IL-6, IL-12, tumor necrosis factor beta (TNF-beta), and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay (ELISA). T-cell function was monitored with T-cell proliferation assays. IL-6 levels rose in eight patients (7.15 +/- 4.38 pg/mL to 86.22 +/- 77.08, p = 0.021). The high-dose group had detectable TNF-betapost rituximab infusion (874.7 +/- 1466.5 pg/mL). There was no decline in T-cell proliferation in response to phytohemagglutinin or allogeneic lymphocyte stimuli. Stimulation indices in the presence of both concentrations of tetanus toxoid rose significantly at 4 weeks.

Adult↗

PubMed2005

Inhibition of AIF-1 expression by constitutive siRNA expression reduces macrophage migration, proliferation, and signal transduction initiated by atherogenic stimuli.

Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, calcium-binding, inflammation-responsive scaffold protein. Several studies have reported increased AIF-1 expression in activated macrophages and have implicated AIF-1 as a marker of activated macrophages. However, the function of AIF-1 in macrophages and the mechanism whereby it participates in macrophage activation are unknown at this time. Immunohistochemical analysis colocalized AIF-1 expression with CD68-positive macrophages in atherosclerotic human coronary arteries. Subsequent experiments were designed to determine a role for AIF-1 in macrophage activation in response to atherogenic stimuli. Stimulation of human and murine macrophages with oxidized LDL significantly increased AIF-1 expression above basal levels. Stable transfection of AIF-1 small interfering RNA (siRNA) in macrophages reduced AIF-1 protein expression by 79% and reduced macrophage proliferation by 52% (P < 0.01). Inhibition of proliferation was not due to induction of apoptosis. Sequences that did not knock down AIF-1 expression had no effect on proliferation. AIF-1 siRNA expression reduced macrophage migration by 60% (P < 0.01). Both proliferation and migration of siRNA-expressing macrophages could be restored by adenoviral expression of AIF-1 (P < 0.001 and 0.005, respectively), suggesting a tight association between AIF-1 expression and macrophage activation. Phosphorylation of Akt, p44/42 MAPK, and p38 kinase were significantly reduced in siRNA macrophages challenged with oxidized LDL (P < 0.05). Phosphorylation of p38 kinase was significantly inhibited in siRNA macrophages stimulated with T lymphocyte conditioned medium (P < 0.05). These data indicate that AIF-1 mediates atherogenesis-initiated signaling and activation of macrophages.

Animals↗

PubMed2004

Hypertrophy, fibrosis, and sudden cardiac death in response to pathological stimuli in mice with mutations in cardiac troponin T.

BACKGROUND: Transgenic mouse models expressing a missense mutation (R92Q) or a splice donor site mutation (trunc) in the cardiac troponin T (cTnT) model familial hypertrophic cardiomyopathy (FHC) in humans. Although males from these strains share the unusual property of having significantly smaller ventricles and cardiac myocytes, they differ with regard to systolic function, fibrosis, and gene expression. Little is known about how these phenotypes affect the responses to additional pathological stimuli. METHODS AND RESULTS: We tested the ability of hearts of both sexes of wild-type and mutant mice to respond to defined pathological, pharmacological, hypertrophic stimuli in vivo. Hearts of mutant cTnT models of both sexes were able to undergo hypertrophy in response to at least one stimulus, but the extent differed between the 2 mutants and was sex specific. Interestingly, the trunc-mutant mouse heart was resistant to the development of fibrosis in response to pharmacological stimuli. Stimulation with 2 adrenergic agonists led to sudden cardiac death of all male but not female mutant animals, which suggests altered adrenergic responsiveness in these 2 models of FHC. CONCLUSIONS: Hypertrophic signaling is differentially affected by distinct mutations in cTnT and is sex modified. Hearts can respond with either an augmented hypertrophic and fibrotic response or a diminished hypertrophy and resistance to fibrosis. Sudden cardiac death is related to adrenergic stress and is independent of the development of fibrosis but occurred only in male mice. These results suggest that patients with certain TnT mutations may respond to certain pathological situations with a worsened phenotype.

Adrenergic alpha-Agonists↗

PubMed2005

Expression of progenitor cell markers during expansion of sorted human pancreatic beta cells.

Functional pancreatic beta cell mass is dynamic and although fully differentiated, beta cells are capable of reentering the cell cycle upon appropriate stimuli. Stimulating regeneration-competent cells in situ is clearly the most desirable way to restore damaged tissue. Regeneration by dedifferentiation and transdifferentiation is a potential source of cells exhibiting a more developmentally immature phenotype and a wide differentiation potential. In this context and to gain a better understanding of the transformation induced in human beta cells during forced in vitro expansion, we focused on identifying differences in gene expression along with phenotypical transformation between proliferating and quiescent human beta cells. FACS-purified beta cells from three different human pancreata were cultured during 3-4 months (8-10 subcultures) on HTB-9 cell matrix with hepatocyte growth factor. Gene expression profiling was performed on cells from each subculture on "in-house" pancreas-specific microarrays consisting of 218 genes and concomitant morphological transformations were studied by immunocytochemistry. Immunocytochemical studies indicated a shift from epithelial to neuroepithelial cell phenotype, including progenitor cell features such as protein gene product 9.5 (PGP 9.5), Reg, vimentin, and neurogenin 3 protein expression. The expression of 49 genes was downregulated, including several markers of endocrine differentiation while 76 were induced by cell expansion including several markers of progenitor cells. Their pattern also argues for the transdifferentiation of beta cells into progenitor cells, demonstrating neuroepithelial features and overexpressing both PBX1, a homeodomain protein that can bind as a heterodimer with PDX1 and could switch the nature of its transcriptional activity, and neurogenin 3, a key factor for the generation of endocrine islet cells. Our study of the machinery that regulates human beta cell expansion and dedifferentiation may help elucidate some of the critical genes that control the formation of adult pancreatic progenitor cells and hence design targets to modify their expression in view of the production of insulin-secreting cells.

Adult↗

PubMed1997

[Possible mechanisms of the anterior limbic cortex influence on the neuron activity of the vago-solitary complex].

In ananesthetized cats, neurons of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNV) revealed phasic excitatory responses to separate single vagal and cortical stimuli. Stimulation of the anterior limbic cortex combined with vagal stimulation resulted in inhibitory or excitatory modification of the vagal induced responses of the NTS and DMNV neurons. The data obtained suggest that complete inhibitory effects are related to general cortical mechanisms of control of the functional state of the brain stem visceral neurons. Selective inhibition of the vagal induced responses by limbic cortex stimulation is due to particular cortical mechanisms of the visceral sensory transmission control via the NTS neurons.

Animals↗

PubMedDate not supplied

Is angiotensin a new pineal hormone?

An isorenin is synthetized in the pineal gland cells. For the synthesis of angiotensin I and II a supply of alpha2 globulin renin substrate is necessary. The amount of isorenin as well as of angiotensin I and II in the pineal gland depends on the circadian rhythm, the sleep-wakefulness cycle, osmotic stimuli, stimulation of the sympathetic postganglionar fibres which innervate the pineal gland and it is increased in some diseases, as hereditary diabetes insipidus and spontaneous hypertension in rat. Pineal angiotensin is released both into the blood and into the cerebrospinal fluid (CSF). The major sites of action are the circumventricular organs, the periventricular receptors of the anterior hypothalamus and the epiphysis cerebri itself. Beside its participation in the regulation of arterial pressure and of the hydroelectrolytic metabolism through its direct effects on the brain, pineal angiotensin also participates in the pool of circulating angiotensin and it may represent Farrell's pineal glomerulotropic factor.

Angiotensin II↗

PubMed1994

A case of Tullio phenomenon in a subject with oval window fistula due to barotrauma.

The Tullio phenomenon is defined as vertigo that occurs as a result of extremely high acoustic stimuli. Stimulation of the system of semicircular canals and otoliths causes nystagmus, reflex head tilt and body sway, and vertigo to occur. This condition is quite rare. The Tullio phenomenon was diagnosed in a patient with a fistula of the oval window due to barotrauma. It was diagnosed after a careful examination by Frenzel's glasses. The complaints of vertigo disappeared after the fistula had been closed surgically.

Adult↗

PubMed2003

Magnetic stimulation of motor and somatosensory cortices suppresses perception of ulnar nerve stimuli.

Magnetic stimulation of sensorimotor cortex interferes with the detection of electro-cutaneous stimulation. However, it is uncertain whether this interference is due to activation of the somatosensory or the motor cortex. Here, transcranial magnetic stimuli (TMS) were delivered separately over somatosensory and motor cortex contralateral to the right ulnar nerve in 12 subjects. In separate trials, TMS were given 100 ms before and 20 ms after 60 ms trains of electro-cutaneous ulnar nerve stimuli, and their effect on the subjective perception of peripheral stimuli was assessed. TMS of both motor and somatosensory cortex interfered with the perception of afferent stimuli when given before or after stimulation of the ulnar nerve. Perception was more strongly suppressed by motor cortex stimulation than by somatosensory cortex stimulation, when given before or after the peripheral stimulus. A similar proportion of errors was induced by sensory cortex stimulation between the two stimulus timing intervals. This study suggests that the inhibition of the afferent volley is unlikely to be the result of antidromic activation of thalamocortical connections or corticospinal gating. A phenomenon akin to sensory masking is the most plausible explanation for much of the suppression of sensory perception by stimulation of the motor or somatosensory cortex. The more powerful suppressive effect of motor cortex stimulation may be due to multiple mechanisms.

Adult↗

PubMed1991

[Changes in neuronal responses of area 7 of the cat cerebral cortex to unconditional and conditional stimulation with additional stimuli].

Influence of external stimuli and food motivation on neuronal spike responses (area 7) induced by conditional and unconditional stimulation were studied in the awake cats. The beginning of external stimuli and food motivation inhibited neuronal responses after electro-cutaneous stimulation. During external stimulation after the reflex onset conditional neuronal reactions were later by 50-250 ms, but the latencies of conditional movements did not change. Identical changes of neuronal responses were during variation of food motivation. It is supposed that the reason of the studied phenomenon is variation of the exteroceptive attention level of cats induced by changes in experiment conditions.

Animals↗

PubMedDate not supplied

[Role of the frontal cortex in organizing emotional-behavioral reactions induced by hypothalamic stimulation and natural stimuli].

Study of the effects of a functional switching off the sensorimotor neocortex area in cats by means of cooling reveals its inhibitory influence on emotional-behavioral reactions to hypothalamic stimulation. Multiple (up to 12) switchings off of the frontal neocortex are attended with a gradual compensation of its inhibitory function by the activity of other brain structures. On the other hand inactivation of the sensorimotor cortex reduces the ability of natural provoking stimuli to lower the thresholds of goal-directed rage which develops when these stimuli are combined with an electrical stimulation of the hypothalamus. A conclusion has been made on the participation of the frontal neocortex in the systemic organization of estimation of biologically significant stimuli.

Anger↗

PubMed1987

Comparative study on effect of N-ethylmaleimide on the superoxide-generating system of guinea-pig eosinophils stimulated by soluble stimuli.

1. The effect of N-ethylmaleimide (MalNEt) modification on O2- production by guinea-pig eosinophils mediated by different soluble stimuli was studied. 2. MalNEt pretreatment inhibited the O2- production stimulated by concanavalin A (Con A), cytochalasin E or digitonin, but not A23187 or sodium fluoride. 3. Particulate fractions from MalNEt-pretreated eosinophils before exposure to the stimulus showed the inhibition of the enhancement of NADPH-dependent O2- production induced by Con A, cytochalasin E or digitonin, but not A23187. 4. Treatment of eosinophils with MalNEt after stimulation had no effect on the NADPH oxidase activity. 5. These findings suggest that at least two pathways exist for the activation of the O2(-)-generating enzyme system, probably the NADPH oxidase system, in guinea-pig eosinophils.

Animals↗

PubMed1988

[Interaction of transcranial magnetic stimulation and mechanical stimuli].

The influence of different mechanical stimuli on the excitability of spinal motoneurones was investigated in 5 different experiments using transcranial magnetic brain stimulation. A servo controlled moving coil was used to deliver rectangular mechanical stimuli or vibration to the right abductor digiti minimi muscle (ADM) thus exciting spindle primaries. With the ADM relaxed, vibration produced an early enhancement of compound responses (CMAPs) after transcranial magnetic brain stimuli. This is thought to be due to simultaneous arrival of the descending corticospinal volley and of the afferent la volley at the anterior horn cell. With long lasting vibration an enhancement of responses to brain stimuli continued up to 5 seconds after the onset of vibration. Voluntary muscle contraction increased the CMAP. CMAPs measured with voluntary muscle contraction plus mechanical muscle stimulation did not differ from those with muscle contraction alone. Therefore an excitatory influence of mechanical stimuli cannot be seen with ADM contracted.

Afferent Pathways↗

PubMed2006

A dense array stimulator to generate arbitrary spatio-temporal tactile stimuli.

The generation and presentation of tactile stimuli presents a unique challenge. Unlike vision and audition, in which standard equipment such as monitors and audio systems can be used for most experiments, tactile stimuli and/or stimulators often have to be tailor-made for a given study. Here, we present a novel tactile stimulator designed to present arbitrary spatio-temporal stimuli to the skin. The stimulator consists of 400 pins, arrayed over a 1cm(2) area, each under independent computer control. The dense array allows for an unprecedented number of stimuli to be presented within an experimental session (e.g., up to 1200 stimuli per minute) and for stimuli to be generated adaptively. The stimulator can be used in a variety of modes and can deliver indented and scanned patterns as well as stimuli defined by mathematical spatio-temporal functions (e.g., drifting sinusoids). We describe the hardware and software of the system, and discuss previous and prospective applications.

Brain Mapping↗

PubMed1993

Perception of olfactory and intranasal trigeminal stimuli following cutaneous electrical stimulation.

Based on previous research it may be hypothesized that the perception of odorants is modified by an axon reflex emanating from trigeminal afferents activated via the skin and/or the intranasal respiratory epithelium. The present experiment investigated the effects of trigeminal cutaneous stimulation on intensity estimates of intranasal chemical stimuli. While the left nostril was stimulated chemically with olfactory and trigeminal stimulants, four regions of the face were stimulated electrically. Intensity estimates of the chemical stimuli tended to increase after cutaneous electrical stimulation which may be interpreted in terms of response priming. The effect of electrical stimulation did not differ at the 4 stimulation sites. The results argue against the hypothesis that the processing of intranasal chemical stimuli is modified peripherally by cutaneous trigeminal excitation.

Adolescent↗

PubMed1989

Calcium is necessary but not sufficient for the platelet-activating factor release in human neutrophils stimulated by physiological stimuli. Role of G-proteins.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; PAF) enhances the release of newly synthesized PAF as measured by [3H]acetate incorporation into PAF in human neutrophils. The response was dose-dependent, rapid, transient, and inhibitable by the PAF antagonist BN-52021. The non-metabolizable bioactive PAF analogue (C-PAF) but not lyso-PAF enhances the release of newly synthesized PAF. Newly synthesized PAF was also released after stimulation of these cells with fMet-Leu-Phe. The human granulocyte-macrophage colony-stimulating factor potentiates the stimulated release of PAF. The intracellular calcium chelator BAPTA inhibits the rise of [Ca2+]i and the release of PAF but not the Na+/H+ antiport activity. PAF release, but not the rise in the intracellular concentration of free calcium, was inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The release of PAF in pertussis toxin-treated cells was also inhibited in cells stimulated with fMet-Leu-Phe or opsonized zymosan. These results suggest that functional pertussis toxin-sensitive guanine nucleotide regulatory protein and/or one or more of the changes produced by phospholipase C activation are necessary for PAF release produced by physiological stimuli. It appears that PAF release requires a coordinated action of receptor-coupled G-proteins, calcium, and other parameters.

Colony-Stimulating Factors↗

PubMed1984

Effect of opiate and adrenergic blockers on the gut motor response to centrally acting stimuli.

Labyrinthine stimulation and cold pain inhibit feeding antral pressure activity, delay gastric emptying, and increase blood concentrations of beta-endorphin and norepinephrine. Further, labyrinthine stimulation induces, in approximately one-third of healthy individuals, a migrating burst of motor activity in the proximal intestine that interrupts the normal fed pattern. Our hypothesis was that endogenous opiates and catecholamines act as mediators of such disruptive effects of centrally acting stressful stimuli on gut motility. Thus, we studied feeding gastrointestinal pressure activity in healthy volunteers who were exposed to labyrinthine stimulation or cold pressure test, or both (both stimuli being either in their active or in their control forms), while receiving an intravenous infusion of either placebo (saline), or an opioid blocker (naloxone), or a combination of alpha- and beta-adrenergic blockers (phentolamine and propranolol), or all the drugs together. Neither opioid nor adrenergic blockers affected motility during control stimulations. Active stressful stimuli (labyrinthine stimulation, cold pain, or both) significantly inhibited antral feeding activity (p less than 0.05), but these effects were prevented by concomitant infusion of naloxone (p less than 0.05). Adrenergic blockade also prevented the antral motor inhibition caused by stress (p less than 0.05), but it was more effective for cold pain than for labyrinthine stimulation, and, when performed concomitantly with opiate blockade, the preventive effects disappeared. Furthermore, during adrenergic blockade labyrinthine stimulation invariably induced the appearance of a migrating duodenal burst of motor activity. Neither opioid nor adrenergic blockers modified the stress-induced rise of plasma beta-endorphin and norepinephrine. Our results suggest that opioids and catecholamines are involved in the mediation of the disruptive effects induced by centrally acting stressful stimuli on postprandial motor activity in the proximal human gut.

Adult↗

PubMedDate not supplied

[Visual system in the light of the study of evoked potentials after stimulation by pattern stimuli in healthy subjects].

In 65 healthy subjects aged 18-70 the characteristics of VEPs elicited with two kind of "pattern reversal" stimulus, checkerboard and gratings, in 13 various configurations were tested. In the recordings the latency and amplitude of peaks P1, N1, P100 and N2, and the difference between maximum and minimum amplitude and correlation coefficient for the cerebral hemispheres were analysed. It was found that checkerboard and gratings elicited in the both hemispheres the responses of comparable latencies and their amplitudes were consequently greater over the left hemisphere. Analyses of the correlation between VEPs and gender showed no influence on latencies and the occurrence of greater amplitudes in females and lower correlation coefficients in males. Differences were noted between potentials evoked by monocular and binocular stimulation, and for the responses elicited with the patterns of checkerboard and gratings, which reflects the activation of two separate channels of the visual system. It was also shown that the characteristics of VEPs obtained using for stimulation the fractionated visual field (checkerboard in the individual hemi-fields and quadrants) was consistent with the topography of visual pathways and retinotopic organisation of the striate cortex, which would suggest a location of the main generator of VEPs in Brodmann's area 17.

Adolescent↗

PubMed1988

Facilitation of muscle responses to magnetic brain stimulation by mechanical stimuli in man.

Transcranial magnetic brain stimuli were applied to 9 normal subjects and compound muscle action potentials were recorded from the right abductor digiti minimi with surface electrodes. Vibration of 120 Hz, 0.6 mm peak to peak amplitude, applied to the muscle tendon enhanced its responses to magnetic brain stimuli. This facilitation corresponds to the tonic vibration reflex. Inhibition of muscle responses was not seen with vibration. Thus it is likely that the known inhibition of stretch reflexes by vibration is purely presynaptic. Small rectangular mechanical stimuli (rise time 200 mm/s, amplitude 1 mm) applied to ADM elicited short and long loop reflex responses. When brain stimuli were give 7-16 ms after the muscle tap, muscle responses were enhanced. It is argued that this is a result of the summation of the effects of Ia afferent impulses and descending pyramidal volleys at the alpha motoneurones. A separate late facilitation corresponding with the arrival of muscle afferent inputs to the sensori-motor cortex was not seen.

Action Potentials↗