SEARCH · PubMed Health

Results for “augmented feedback”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed2000

Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels.

A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (ICa) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for ICa facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent ICa facilitation.

Animals↗

PubMed2006

Equipment and technology in surgical robotics.

Contemporary medical robotic systems used in urologic surgery usually consist of a computer and a mechanical device to carry out the designated task with an image acquisition module. These systems are typically from one of the two categories: offline or online robots. Offline robots, also known as fixed path robots, are completely automated with pre-programmed motion planning based on pre-operative imaging studies where precise movements within set confines are carried out. Online robotic systems rely on continuous input from the surgeons and change their movements and actions according to the input in real time. This class of robots is further divided into endoscopic manipulators and master-slave robotic systems. Current robotic surgical systems have resulted in a paradigm shift in the minimally invasive approach to complex laparoscopic urological procedures. Future developments will focus on refining haptic feedback, system miniaturization and improved augmented reality and telesurgical capabilities.

Humans↗

PubMed2001

Activation of phosphodiesterase 5 and inhibition of guanylate cyclase by cGMP-dependent protein kinase in smooth muscle.

The regulation of cGMP-specific phosphodiesterase (PDE) 5 and soluble guanylate cyclase (GC) by cGMP- and cAMP-dependent protein kinases (PKG and PKA respectively) was examined in gastric smooth muscle. The NO donor, sodium nitroprusside (SNP), stimulated PDE5 phosphorylation and activity, which was blocked by the selective PKG inhibitor, KT5823, resulting in an elevation of cGMP levels. Activation of PKA either directly by Sp-5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole 3',5'-cyclic monophosphothioate, or via isoproterenol- and forskolin-dependent increase in cAMP, also caused an increase in PDE5 phosphorylation and activity, but only in the presence of cGMP; consistent with the dependence of PDE5 phosphorylation and activity on cGMP binding to allosteric sites in the regulatory domain of PDE5. The selective PKA inhibitors, myristoylated protein kinase inhibitor and H-89, blocked the increase in PDE5 phosphorylation and activity induced by PKA. SNP also stimulated soluble GC phosphorylation and activity. KT5823 abolished phosphorylation and augmented soluble GC activity, implying feedback inhibition of soluble GC by PKG-dependent phosphorylation. Phosphorylation by PKG was direct and could be induced in vitro. Activation of PKA had no effect on soluble GC. Thus cGMP levels are regulated by PKG- and PKA-dependent activation of PDE5 and PKG-specific inhibition of soluble GC.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1991

Serum interleukin-6 concentrations are elevated and associated with elevated tumor necrosis factor-alpha and immunoglobulin G and A concentrations in children with HIV infection.

Hypergammaglobulinemia is one of the most consistent, and usually the first observable abnormality in infants vertically infected with HIV. We have analyzed serum interleukin (IL)-4, IL-6, tumor necrosis factor (TNF)-alpha, and immunoglobulin (Ig) concentrations in 23 HIV-infected and 21 uninfected children. IL-6 and TNF-alpha concentrations in HIV-infected children were significantly higher than those in uninfected children, and mutually correlated. No differences in serum IL-4 levels between infected and uninfected children were observed. There was a correlation between serum IL-6 and IgG and between IL-6 and IgA concentrations. Furthermore, during follow-up changes in IL-6 levels were usually accompanied by corresponding changes in IgG levels. Our data indicate an association between HIV, IL-6, TNF-alpha and hypergammaglobulinemia. Regardless of the source and initial stimulus, continued production of IL-6 and TNF-alpha may result in augmentation in an auto-feedback manner, accompanied by increases in Ig synthesis and, more importantly, HIV replication. Thus, elucidation of the mechanisms responsible for overproduction of these two cytokines in HIV-infected patients is not only interesting from a biologic point of view, but is likely to have important clinical implications as well.

B-Lymphocytes↗

PubMed2001

Fatiguing inspiratory muscle work causes reflex reduction in resting leg blood flow in humans.

1. We recently showed that fatigue of the inspiratory muscles via voluntary efforts caused a time-dependent increase in limb muscle sympathetic nerve activity (MSNA) (St Croix et al. 2000). We now asked whether limb muscle vasoconstriction and reduction in limb blood flow also accompany inspiratory muscle fatigue. 2. In six healthy human subjects at rest, we measured leg blood flow (.Q(L)) in the femoral artery with Doppler ultrasound techniques and calculated limb vascular resistance (LVR) while subjects performed two types of fatiguing inspiratory work to the point of task failure (3-10 min). Subjects inspired primarily with their diaphragm through a resistor, generating (i) 60 % maximal inspiratory mouth pressure (P(M)) and a prolonged duty cycle (T(I)/T(TOT) = 0.7); and (ii) 60 % maximal P(M) and a T(I)/T(TOT) of 0.4. The first type of exercise caused prolonged ischaemia of the diaphragm during each inspiration. The second type fatigued the diaphragm with briefer periods of ischaemia using a shorter duty cycle and a higher frequency of contraction. End-tidal P(CO2) was maintained by increasing the inspired CO(2) fraction (F(I,CO2)) as needed. Both trials caused a 25-40 % reduction in diaphragm force production in response to bilateral phrenic nerve stimulation. 3. .Q(L) and LVR were unchanged during the first minute of the fatigue trials in most subjects; however, .Q(L) subsequently decreased (-30 %) and LVR increased (50-60 %) relative to control in a time-dependent manner. This effect was present by 2 min in all subjects. During recovery, the observed changes dissipated quickly (< 30 s). Mean arterial pressure (MAP; +4-13 mmHg) and heart rate (+16-20 beats min(-1)) increased during fatiguing diaphragm contractions. 4. When central inspiratory motor output was increased for 2 min without diaphragm fatigue by increasing either inspiratory force output (95 % of maximal inspiratory pressure (MIP)) or inspiratory flow rate (5 x eupnoea), .Q(L), MAP and LVR were unchanged; although continuing the high force output trials for 3 min did cause a relatively small but significant increase in LVR and a reduction in .Q(L). 5. When the breathing pattern of the fatiguing trials was mimicked with no added resistance, LVR was reduced and .Q(L) increased significantly; these changes were attributed to the negative feedback effects on MSNA from augmented tidal volume. 6. Voluntary increases in inspiratory effort, in the absence of diaphragm fatigue, had no effect on .Q(L) and LVR, whereas the two types of diaphragm-fatiguing trials elicited decreases in .Q(L) and increases in LVR. We attribute these changes to a metaboreflex originating in the diaphragm. Diaphragm and forearm muscle fatigue showed very similar time-dependent effects on LVR and .Q(L).

Adult↗

PubMed1997

Pathophysiological mechanisms of hearing loss.

An understanding of auditory transduction in the ear can contribute to a better comprehension of the pathophysiological mechanisms which give rise to hearing loss. The incoming sound sets up a mechanical traveling wave which begins at the base and progresses along the basilar membrane, reaching a point of maximal displacement. The region of maximal displacement is a function of stimulus frequency. The mechanical displacement, by directly opening ion channels in the stereocilia of the hair cells, induces changes in the electrical potential of the hair cells. This initial stage is called mechano-electrical transduction, and in the normal ear, is followed by a stage of electro-mechanical transduction based on the ability of the outer hair cells to respond to the electrical changes induced in them with a change in their length. This "electromotility" presumably provides mechanical feedback to the basilar membrane, augmenting its mechanical displacement. This is called the cochlear amplifier, providing the ear with improved sensitivity and frequency discrimination. Most forms of sensori-neural hearing losses (affecting the inner ear) are due to a lesion to some part of this cochlear amplifier (e.g. noise induced hearing loss, ototoxic drugs) and are therefore characterized by auditory threshold elevations and poorer frequency discrimination.

Acoustic Stimulation↗

PubMed1982

Comparison of mildly mentally retarded and nonretarded children on a rotary pursuit task under optimal task conditions.

The performance of 80 mildly mentally retarded and 133 nonretarded children were compared on a rotary pursuit task to determine whether augmentation of response-produced feedback by supplementary sensory feedback would facilitate acquisition. The presentation methods and modes of sensory feedback were also examined to determine whether equity in acquisition between the mildly retarded and their nonretarded counterparts could be achieved. All subjects were assigned randomly to selected feedback treatments, yielding four mildly retarded and seven nonretarded groups. Acquisition of the rotary pursuit task was achieved by all subjects under response-produced and supplementary feedback conditions; however, acquisition in selected groups in the mildly retarded category was enhanced to a greater degree by the additional feedback than in their nonretarded counterparts.

Adolescent↗

PubMed2006

Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop?

The cell-adhesion molecule CD44 likely participates in atherosclerosis development. We have shown previously that pro-inflammatory cytokines affect CD44 expression. Therefore, this work examined the role of elevated CD44 levels in human macrophages. Macrophages from human atherosclerotic subjects (n=15) showed elevated levels of CD44 transcript and protein (1.5-fold) compared to matched controls (n=15) (P=0.050 and 0.044, respectively). To test whether genetic factors influence CD44 expression, two single nucleotide polymorphisms in the CD44 gene were analyzed but these were not associated with coronary artery disease. We also examined the potential connection between plasma cytokine levels and CD44 expression. In atherosclerotic subjects, elevated CD44 expression correlates (P=0.012) with enhanced macrophage IL-6 secretion (3.13+/-2.5 pg/mL versus 0.32+/-0.16 pg/mL in controls, P=0.021). Additionally, CD44-deficient mice exhibit less circulating IL-6 than wild-type controls (9.8+/-0.7 pg/mL versus 14.3+/-0.7 pg/mL; P=0.032). Furthermore, IL-6 augments CD44 expression in primary human macrophages after 24 h (P=0.038) and 48 h (P=0.015). Taken together, our data show an IL-6-CD44 feedback loop in macrophages. Such a positive feedback loop may aggravate atherosclerosis development.

Animals↗

PubMed1995

Continuous administration of human corticotropin-releasing hormone in the absence of glucocorticoid feedback in man.

Continuous 24-hour infusions of a maximally stimulating dose (1 microgram/kg/h) of corticotropin-releasing hormone (CRH) have been shown to cause elevations of plasma cortisol and ACTH, but the pattern of results were confounded by serum cortisol causing feedback changes. We have looked at ACTH responses to saline or CRH infusions over 24 h in 6 normal subjects who, in addition, received either placebo or metyrapone, an 11 beta-hydroxylase inhibitor which blocks the formation of cortisol and thus abolishes glucocorticoid feedback. Cortisol and ACTH levels were measured by radioimmunoassay. Before metyrapone, CRH infusion resulted in exaggerated ACTH peaks throughout the day, as compared with normal saline: there was no influence on the noctural rise in ACTH. Following metyrapone alone, absolute cortisol levels were lower but circadian rhythmicity was preserved. Circadian rhythm of ACTH was maintained, with a fall in the evening to 14.5 +/- 4 pg/ml (mean +/- SE) at midnight and an exaggerated rise overnight, reaching a peak level of 90 +/- 33 pg/ml at 07:00 h. Subjects receiving CRH with metyrapone showed a similar pattern of responses, but with further enhanced ACTH levels. The evening fall reached a nadir of 30 +/- 6 pg/ml at 01:00 h. With diminished glucocorticoid feedback the nocturnal rise in ACTH was augmented by CRH infusion, with a morning peak of 193 +/- 21 pg/ml at 07:00 h. Thus, continuous infusion of CRH in the absence of steroid feedback leads to a retention of the circadian rhythmicity in ACTH secretion, reset at a higher absolute level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMed2003

Constructing a feedback loop with circadian clock molecules from the silkmoth, Antheraea pernyi.

Circadian clocks are important regulators of behavior and physiology. The circadian clock of Drosophila depends on an autoinhibitory feedback loop involving dCLOCK, CYCLE (also called dBMAL, for Drosophila brain and muscle ARNT-like protein), dPERIOD, and dTIMELESS. Recent studies suggest that the clock mechanism in other insect species may differ strikingly from that of Drosophila. We cloned Clock, Bmal, and Timeless homologs (apClock, apBmal, and apTimeless) from the silkmoth Antheraea pernyi, from which a Period homolog (apPeriod) has already been cloned. In Schneider 2 (S2) cell culture assays, apCLOCK:apBMAL activates transcription through an E-box enhancer element found in the 5' region of the apPeriod gene. Furthermore, apPERIOD can robustly inhibit apCLOCK: apBMAL-mediated transactivation, and apTIMELESS can augment this inhibition. Thus, a complete feedback loop, resembling that found in Drosophila, can be constructed from silkmoth CLOCK, BMAL, PERIOD, and TIMELESS. Our results suggest that the circadian autoinhibitory feedback loop discovered in Drosophila is likely to be widespread among insects. However, whereas the transactivation domain in Drosophila lies in the C terminus of dCLOCK, in A. pernyi, it lies in the C terminus of apBMAL, which is highly conserved with the C termini of BMALs in other insects (except Drosophila) and in vertebrates. Our analysis sheds light on the molecular function and evolution of clock genes in the animal kingdom.

ARNTL Transcription Factors↗

PubMed1984

Effects of 6-hydroxydopamine treatment of rats on the in-vitro release of LHRH and pituitary responsiveness to LHRH.

Injection of 150 micrograms 6-hydroxydopamine (6-OHDA) into the third ventricle of rats depleted the mean hypothalamic concentration of noradrenaline by 71% whereas the mean dopamine concentration was only reduced by an insignificant 7%. Isolated perfused pituitary glands taken from intact 6-OHDA-treated rats showed a markedly increased LH response to pulses of LHRH although there was no significant difference in the circulating levels of LH. Ovarian cyclicity was disrupted and the hypothalamic content of LHRH was significantly reduced. Hypothalamic synaptosomes prepared from intact 6-OHDA-treated animals consistently released less LHRH than did controls although the difference was not significant. Noradrenaline, dopamine and adrenaline did not significantly affect LHRH release from experimental or control synaptosome preparations. In ovariectomized rats 6-OHDA treatment did not inhibit the positive feedback effects of progesterone administration to oestrogen-primed animals, although the negative feedback effects of the priming oestrogen treatment was augmented. The results indicate that depletion of hypothalamic noradrenaline causes subtle changes in the endogenous release of LHRH and may alter the negative feedback effects of steroids on the hypothalamic-pituitary axis.

Animals↗

PubMed2006

Novel functions of small conductance Ca2+-activated K+ channel in enhanced cell proliferation by ATP in brain endothelial cells.

Brain capillary endothelial cells (BCECs) form the blood-brain barrier (BBB), which is essential for maintaining homeostasis of the brain. Net cellular turnover, which results from the balance between cell death and proliferation, is important in maintaining BBB homeostasis. Here we report a novel mechanism that underlies ATP-induced cell proliferation in t-BBEC 117, a cell line derived from bovine brain endothelial cells. Application of 0.1-30 mum ATP to t-BBEC 117 concentration-dependently increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in two phases: an initial transient phase and a later and smaller sustained one. These two phases of [Ca(2+)](i) rise were mainly due to Ca(2+) release and sustained Ca(2+) influx, respectively. The pretreatment with apamin, a selective blocker of small conductance Ca(2+)-activated K(+) channels (SK), significantly reduced both the [Ca(2+)](i) increase and K(+) current induced by ATP. Transcripts corresponding to P2Yx, SK2, and transient receptor potential channels were detected in t-BBEC 117. Knock down of SK2 protein, which was the predominant Ca(2+)-activated K(+) channel expressed in t-BBEC 117, by siRNA significantly reduced both the sustained phase of the [Ca(2+)](i) rise and the K(+) current induced by ATP. Cell proliferation was increased significantly by the presence of the stable ATP analogue ATPgammaS. This effect was blunted by UCL1684, a synthesized SK blocker. In conclusion, in brain endothelial cells ATP-induced [Ca(2+)](i) rise activates SK2 current, and the subsequent membrane hyperpolarization enhances Ca(2+) entry presumably through transient receptor potential channels. This positive feedback mechanism can account for the augmented cell proliferation by ATP.

Adenosine Triphosphate↗

PubMed2005

Steroid hormones regulate gene expression posttranscriptionally by altering the stabilities of messenger RNAs.

Hormones exert powerful effects on reproductive physiology by regulating gene expression. Recent discoveries in hormone action emphasize that regulation of gene expression is not restricted to their alterations of the rate of gene transcription. On the contrary, hormonal effects on the stability of a specific mRNA can profoundly alter its steady-state concentration. The mRNAs encoding hormone receptors are commonly regulated by their own hormones to create autoregulatory feedback loops. Negative and positive autoregulatory feedback loops serve to limit or augment hormonal responses, respectively. After introducing the topics of mRNA degradation and regulated stability, this review focuses on steroid hormone effects on mRNA stabilities. Autoregulation of the mRNAs encoding estrogen, progesterone, androgen, and glucocorticoid receptors by the steroid hormones in reproductive tissues is discussed. In addition, steroid hormone effects on the stabilities of many other mRNAs that are important to reproductive biology are reviewed. These include mRNAs that encode gonadotropin hormones, integrins, growth factors, and inflammatory response proteins. Through these posttranscriptional effects, steroid hormones impact the expression of a large population of genes. Studies of the molecular mechanisms of hormonally regulated mRNA stabilities continue to identify critical mRNA sequence elements and their interactions with proteins. Increased understanding of how hormones affect mRNA stability may yield novel approaches to the therapeutic control of hormone effects, including those essential to reproductive physiology in animals.

Animals↗

PubMed1996

Calyculin A, a phosphoprotein phosphatase inhibitor, stimulates acid secretion in isolated gastric glands.

The effects of pkadaic acid (OKA) and calyculin A (CLA), inhibitors of protein phosphatases type 1 (PrPase1) and type 2A (PrPase2A), an acid secretion were examined in rabbit isolated gastric gland, CLA, but not OKA, strongly stimulated acid secretion by itself without affecting glandular adenosine 3',5'-cyclic monophosphate (cAMP) contents. CLA-induced secretion was suggested to be mainly due to the increase in the phosphorylation of protein kinase A substrates via the inhibition of PrPase1 in the parietal cell, since 1) CLA-induced secretion was not inhibited by cimetidine or atropine, 2) a protein kinase A inhibitor inhibited the secretion, whereas a protein kinase C inhibitor did not, 3) CLA augmented dibutyryl cAMP-induced secretion in some cases, and 4) OKA, which is 100 times more selective to PrPase2A than to PrPase1, was not a secretagogue. Unexpectedly, CLA did not augment the secretion by histamine, possibly because the inhibitor augmented the phosphorylation-mediating negative feedback pathway as well. Both CLA and OKA markedly increased phosphorylation of ezrin, a putative protein kinase A substrate, in the course of secretory activation.

4-Nitrophenylphosphatase↗

PubMed1984

Avenues of investigation for the role of catecholamines in anxiety.

Many of the cardinal somatic symptoms associated with anxiety states are produced by the sympathoadrenal medullary discharge of catecholamines (CA) described over 50 years ago as 'fight or flight' responses. During the last decade, development of sensitive convenient assays for CA and their metabolites in tissues, cerebrospinal fluid, plasma and urine has made possible assessment of brain and peripheral adrenergic activity during stress, in neuropsychiatric disorders, and after administration of drugs. Studies in animal models of stress and anxiety parallel studies in humans. In rats, there are genetic differences in the graded adrenergic alerting responses to administered or anticipated stress, analogous to trait anxiety in humans. Behavioral responses to stress may be attenuated in rats by pharmacological blockade of peripheral CA release, suggesting a positive feedback process in which released CA augment behavioral responses, possibly analogous to use of clonidine or beta-adrenergic blocking agents to diminish somatic symptoms attending anxiety-provoking situations in humans. The biochemical evaluation of adrenergic responses by examination of CA and their metabolites in body fluids of humans with various levels of sympathetic activation will be discussed.

Adrenal Medulla↗

PubMed1983

Regulation of the immune response to alloantigens: suppressor and helper T cells generated in the primary MLR of the rat.

The primary MLR of the rat was used to generate suppressor, cytotoxic, and helper T cells from lymph node cells of the WF (RT1 mu) inbred strain. They were assayed in 51Cr-release cytotoxic assays and by their effect on proliferation of fresh unprimed responder cells. Suppression by MLR cellular products was antigen-specific and generation and functional expression were directed to class II (RT1.B,D) antigens of stimulator cells in the strains tested. In contrast, help was not antigen-specific. The monoclonal antibodies OX8 and W3/25 were used to separate the primed products of the MLR into the constitutive subsets, suppressor/cytotoxic (OX8+) and helper/inducer (W3/25+). Gamma irradiation of OX8+ MLR-primed cells caused modest reductions in suppressive activity, but had no effect on the helper activity of W3/25+ cells. MLR-derived suppressor cells are effective only when added in the early stages of the test primary MLR, whereas helper cells can augment proliferation even when added late. Feedback suppression is not mediated by classical cytotoxic T cells, because of differences in kinetics of development, cell numbers required, susceptibility to freezing, and expression of the RT6 differentiation antigen.

Animals↗

PubMed1982

Effects of thoracic dorsal rhizotomy or vagotomy on inspiratory muscle activity at various levels of chemical drive.

The relationship between relative peak activity (moving average EMG) of the diaphragm (Adi) and of the cranial (2nd and 3rd) external intercostal or parasternal muscles (Aic) was assessed during rebreathing in animals before and after bilateral thoracic (T1-T4) dorsal rhizotomy (TDR) and/or bilateral vagotomy (VGT). The relationship had the form Aic=a Adib under all conditions. In intact rabbits and cats mean values for b were 1.48 and 1.79, respectively, a being unity by definition. Neither TDR nor VGT changed b; a decreased to about 0.15 with TDR and halved with VGT only if performed before TDR. Selective reflex facilitation of inspiratory intercostals with occlusions at FRC was observed after VGT and was abolished by TDR. Neither VGT nor TDR affected Adi time course. Hence: (1) central command to alpha-motoneurones of the major inspiratory muscles differs; (2) proprioceptive feedback markedly increases external intercostal activity, apparently by multiplying Aic due to central command to alpha-motoneurones by a factor independent of chemical drive; (3) vagally mediated augmentation of Aic depends entirely on intact proprioceptive feedback. The possible role of fusimotor drive is discussed.

Animals↗

PubMed1991

Cardiovascular and respiratory control mechanisms during exercise: an integrated view.

Exercise can impose an immense stress upon many physiological systems throughout the body. In order that exercise performance may be optimally maintained, it is essential that a profound and complex series of responses is coordinated and controlled. The primary site for coordination is the central nervous system, whereas control mechanisms (both feedback loops and feedforward activation) involve complex sensory information, often in the form of neural coding but also in the form of blood-borne chemical signals, a number of levels of peripheral and central integration and, finally, the efferent branches of the nervous system coursing via sympathetic and parasympathetic nerves to target sites of action. The neurohumoral control of the cardiorespiratory responses to exercise has received intense attention for over two decades and some particularly important steps forward in its understanding have occurred within the last 10 years. The initial fast increase (phase 1) in cardiovascular and ventilatory flow parameters are brought about by neurally mediated muscle mechanoreceptor feedback reflexes and a feedforward 'central motor command'. The blood pressure operating point is also raised by a combination of these two neural mechanisms. Fine control of the matching of cardiac output to ventilation may occur by means of a feedforward ventilatory control of cardiac origin. During the slower phase of adjustment (phase 2), the neurally mediated mechanisms are augmented by a cohort of humorally mediated feedback reflexes involving muscle and vascular chemoreceptors as well as being supported by central neural reverberation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗