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A functional role for the tubuloglomerular feedback mechanism.

Ever increasing evidence exists that the tubuloglomerular feedback system exerts a major influence on overall renal function. Several examples are potentially pertinent to clinical medicine in which there is reasonable evidence that activation or suppression of tubuloglomerular feedback mechanisms contribute significantly to alterations in normal renal physiology. However, in most examples reported, the feedback mechanism is one of several influences acting in concert to determine the final nephron filtration rate, its respective determinants, and the relationship of filtration to the rate of tubular reabsorption. A more complete understanding of all the factors which influence and modify the functional role of tubuloglomerular feedback mechanisms will aid our understanding significantly and the consequent therapy of a variety of altered physiologic conditions.

Acute Kidney Injury↗

Quantitative control analysis of branched-chain 2-oxo acid dehydrogenase complex activity by feedback inhibition.

The potential for branched-chain 2-oxo acid dehydrogenase complex (BCOADC) activity to be controlled by feedback inhibition was investigated by calculating the Elasticity Coefficients for several feedback inhibitors. We suggest that feedback inhibition is a quantitatively important regulatory mechanism by which branched-chain 2-oxo acid dehydrogenase activity is regulated. The potential for control of enzyme activity is greater for NADH than for the acyl-CoA products, and suggests that factors that alter the redox potential may physiologically regulate BCOADC activity through a feedback inhibitory mechanism in vivo. Local pH may also be an important regulatory control factor.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Feedback-mediated reduction in glomerular filtration during acetazolamide infusion in insulin-dependent diabetic patients.

1. A sustained high glomerular filtration rate in diabetes mellitus is associated with increased proximal reabsorption, suggesting alterations in the tubuloglomerular feedback system. To test this hypothesis, renal function was studied in eight control subjects and 14 recent-onset euglycaemic insulin-dependent diabetic patients before and after infusion of the carbonic anhydrase inhibitor, acetazolamide (5 mg/kg body weight). 2. Acetazolamide induced a dramatic fall in glomerular filtration rate in both diabetic patients and control subjects (from 138 +/- 5 to 114 +/- 4 and from 127 +/- 3 to 113 +/- 2 ml min-1 1.73 m-2, respectively, P less than 0.0001). This fall in glomerular filtration rate was strongly correlated with the acetazolamide-induced decrease in absolute proximal reabsorption calculated by using lithium clearance. 3. To further assess the potential role of angiotensin II in the acetazolamide-induced tubulo-glomerular feedback response, 11 additional diabetic patients were investigated before and after the administration of acetazolamide plus the angiotensin-converting enzyme inhibitor, enalaprilat (1.25 mg intravenously). Despite the effective blockade of angiotensin II formation and a slight decrease in renal vascular resistance, the glomerular filtration rate fell significantly and by a similar magnitude as seen with acetazolamide alone. 4. These results indirectly suggest that there is an altered basal tubulo-glomerular feedback system in diabetic patients but a normal response to the increase in distal delivery. No convincing role for an angiotensin II-mediated effect on the afferent limb of the tubuloglomerular feedback response could be demonstrated.

Acetazolamide↗

Effect of altered auditory feedback on people who stutter during scripted telephone conversations.

The effect of altered auditory feedback (AAF) conditions on stuttering during scripted telephone conversations was investigated. Nine adult participants made 15 scripted telephone calls to business in New York City. Alterations in the participants' auditory feedback signal were generated by a commercially available digital signal processor (Casa Futura Technologies Desktop Fluency System Model BTD-400) that shifted participants' speech one-half octave down in frequency, produced a 50-ms delay, or produced non-altered auditory feedback. The AAF effects produced by the digital signal processor were not perceived by the recipients of the telephone calls. The proportion of stuttering events per scripted telephone conversations were significantly reduced in the AAF conditions relative to the non-altered auditory feedback condition (p = .0004). Stuttering frequency was reduced by 55% and 60% for the FAF and DAF, respectively. These findings demonstrate the applicability of this technology to situations of daily living involving telephone use.

Adult↗

Effects of monitoring condition and frequency-altered feedback on stuttering frequency.

The purpose of the study was to examine stuttering frequency during speaking conditions that are believed to mitigate stuttering frequency both with normal nonaltered auditory feedback (NAF) and a known fluency-enhancing feedback. Specifically, stuttering frequency was examined as a function of three monitoring conditions under NAF and frequency-altered feedback (FAF): no monitoring (i.e., speaking alone, in the absence of audio and visual recording), audiovisual monitoring (i.e., speaking alone with audiovisual recording), and audiovisual monitoring with observers (i.e., speaking with audiovisual recording in the presence of two observers). Seven adults and one adolescent who stutter served as participants. Stuttering frequency was differentially affected across monitoring conditions under each auditory feedback condition (p = .027). Post hoc analyses revealed no significant difference in stuttering frequency between the two conditions in the absence of the observers (i.e., no monitoring vs. audiovisual monitoring) under NAF (p = .45). There was, however, a significant difference in stuttering frequency for the no-monitoring and audiovisual-monitoring conditions relative to the audiovisual-monitoring-with-observers condition (p = .0002). There was no statistically significant difference in stuttering frequency across monitoring conditions under FAF (p > .05). The findings are consistent with the notion that during NAF stuttering frequency varies as a function of hierarchical socio-environmental conditions in which inanimate monitoring conditions constitute one entity. Such a relationship does not exist during FAF.

Adult↗

Early environmental regulation of glucocorticoid feedback sensitivity in young adult monkeys.

Variations in maternal care induce in neonatal rodents life-long changes in glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis. This aspect of plasticity in neuroendocrine development has not been established in primates. We assessed, in young adult squirrel monkeys, postnatal rearing effects on cortisol-induced suppression of corticotropin-releasing factor (CRF) stimulated secretion of adrenocorticotropic hormone (ACTH). Offspring of randomly bred monkeys were periodically removed from natal groups between 13 and 21 weeks of age. In two other postnatal rearing conditions, systematic differences in maternal availability were produced by manipulating the effort required of lactating mothers to successfully find food. All offspring were subsequently administered, 3-5 years later on two occasions, an intravenous ovine CRF injection preceded 60 min earlier by placebo or cortisol pretreatment. The difference between CRF-stimulated time-integrated secretion of ACTH following placebo vs cortisol pretreatment served as an index of glucocorticoid negative feedback. Difference scores were greatest in monkeys previously separated from natal groups. This finding was not attributable to significant rearing condition differences in plasma cortisol levels achieved following pretreatment with exogenous cortisol, nor plasma ACTH levels produced when the CRF injection was preceded by pretreatment with placebo. The results suggest that postnatal experiences altered glucocorticoid feedback in monkeys at least through early adulthood. This conclusion supports retrospective reports indicating that, for humans with major mood and anxiety disorders, systematic differences in glucocorticoid feedback may reflect neural mechanisms in development linking early life stress with psychopathology in adulthood.

Adaptation, Physiological↗

The effect of feedback on anxiety levels during ultrasound scanning for ovarian cancer.

Women undergoing ultrasound scanning for the detection of ovarian cancer benefit psychologically from the examination, which has been shown to reduce levels of anxiety, depression, hostility and complaints about somatic symptoms. However, it is not completely clear what aspects of the ultrasound examination are responsible for these effects, and how these beneficial psychological effects vary under different circumstances. This study examined, in particular, the effect of various levels of feedback on patients' anxiety levels before and after ultrasound examination. Two hundred and seven women were randomly assigned to two different experimental conditions: high feedback and low feedback. The subjects' levels of anxiety (both trait and state anxiety) were measured immediately before and after the ultrasound examination. The women's individual risk factors for ovarian cancer were also recorded. This study showed a significant decrease in the level of trait anxiety following ultrasound scanning. The decrease in anxiety did not relate to the level of feedback provided to the patients, nor to the woman's degree of risk for ovarian cancer. The results are discussed in terms of possible implications for clinical care and the allocation of resources in the medical system.

Adolescent↗

Effect of education and performance feedback on handwashing: the benefit of administrative support in Argentinean hospitals.

BACKGROUND: Patients admitted to hospitals are at risk of acquiring nosocomial infections. Many peer-reviewed studies show that handwashing (HW) significantly reduces hospital infections and mortality. Our objective was to evaluate the effects of HW by health care workers (HCW) before contact with patients in 3 Argentinean hospitals. We performed an observational study of HCW to measure the effect of 2 interventions: education alone and education plus performance feedback. METHODS: A total of 3 hospitals were studied for adherence to a HW protocol. The observed HCW included physicians, nursing personnel, and ancillary staff. After initial observations to establish baseline rates of HW (phase 1), we evaluated the effect of education alone (phase 2), followed by education plus performance feedback (phase 3). We also evaluated the relationship between the administrative support and HW adherence. RESULTS: We observed 15,531 patient contacts in 3 hospitals. The baseline rate of HW before contact with patients was 17%. With education, HW before contact with the patients increased to 44% (relative risk 2.65; 95% confidence interval 2.33-3.02; P <.001). Using education and performance feedback HW further increased to 58% (relative risk 1.86; 95% confidence interval 1.38-2.51; P <.001). In the private hospitals where administrative support for the HW program was significantly greater, HW compliance was significantly higher (logistic regression analysis: odds ratio 5.57; 95% confidence interval 5.25-6.31; P <.001). CONCLUSIONS: In this study, HW policies and education of HCW significantly improved HCW adherence to the HW protocol, however, when performance feedback was incorporated, the HW compliance increased to a greater degree. We identified that administrative support provides a positive influence in efforts to improve HW adherence.

Analysis of Variance↗

The effects of augmented sensory feedback precision on the acquisition and retention of a simulated chiropractic task.

OBJECTIVE: To examine the effectiveness of knowledge of results precision in the acquisition and retention of a simulated manipulative procedure. DESIGN: A controlled trial was conducted, with subjects assigned to 1 of 2 interventions by means of a stratified random technique. METHODS: Seventy-one healthy male and female chiropractic student volunteers were asked to control the application of force of a simulated chiropractic manipulative procedure. Two feedback conditions (quantitative and qualitative), 2 performance conditions (light and heavy force levels), and 3 delay intervals (1, 5, and 8 days) were studied. Acquisition trials were divided into 10 blocks of 5 trials for a total of 50 trials. All subjects performed 2 blocks of 10 trials (total of 20 trials) during the no-feedback retention phase. Absolute constant error (/CE/) was analyzed as the measure of performance accuracy, and variable error (VE) was used to determine performance consistency. RESULTS: No significant main effect for the 2 feedback groups was found for /CE/ and VE during the acquisition phase. A significant main effect for force was found for /CE/ and VE, indicating that subjects were more accurate during light conditions than heavy conditions. There was a significant main effect for trial blocks for both /CE/ and VE, indicating that groups became more accurate and consistent as a result of practice. During the retention phase, a significant main effect for retention group conditions was identified for /CE/ but not for VE. This indicates that the retention groups differed in accuracy but were similar in consistency. Post hoc analyses indicated that subjects were less accurate as time between acquisition and retention trials increased. There was a significant main effect for trial blocks for VE but not for /CE/, suggesting that groups became more consistent between trial blocks. A significant group trial block interaction was revealed for /CE/. No other main effects or interactions in the analyses were significant for /CE/ or VE. CONCLUSION: The findings of this study suggest that practice sessions with kinetic devices (simulators) and performance feedback, whether quantitative or qualitative, may be useful when implemented to assist the performance of complex motor skills. There is not enough evidence to support the idea that the training used in this study could generate lasting learning effects.

Adult↗

Feedback versus an illusion in time.

The accuracy of many perceptual comparisons depends greatly on the order in which the to-be-compared stimuli are presented. With comparisons of durations around 300 ms, these presentation-order effects do not diminish, even with extended practice, when feedback about response accuracy is withheld. Providing such feedback greatly diminishes presentation-order effects and coincidentally produces substantial increases in response accuracy. The feedback acts in part through inducing response biases and in part through changes in sensitivity. The contradiction between studies which report time-order errors in duration comparison and those which do not is attributable to differences in the use of information feedback.

Discrimination, Psychological↗

Opioid involvement in LH release during the negative feedback effects of oestradiol and progesterone in dairy cows.

To create a clearly defined and uniform feedback phase of oestradiol, 1 mg oestradiol benzoate (OE2) was injected i.m. either 15-43 days post partum in 7 cows (Expt 1), or 12 h after prostaglandin oestrus synchronization of 4 cyclic cows (Expt 2 and 3). An endogenous opioid peptide (EOP) antagonist (250 mg naloxone), an EOP agonist (300 mg morphine), or a combination of the two was given in Expt 1, 2 and 3 respectively as a single i.v. injection in cows 16-18 h after OE2, i.e. in the negative feedback phase and before the expected onset of an induced luteinizing hormone (LH) surge. Blood samples were collected every 15 min for 1 h before and 2 h after each treatment. In Expt 1, naloxone failed to increase LH release when given during the negative feedback phase, but caused excessive release in one cow in which the LH surge had just begun. In all cows in Expt 2, morphine suppressed LH release (P less than 0.05). In Expt 3, naloxone prevented the suppressive effects of morphine for the first hour after treatment; a transient rise in LH occurred in one cow in which treatment was given 1 h before the start of the LH surge. In Expt 4, 250 mg naloxone was injected i.v. into 4 cows that had a plasma progesterone concentration of 1.5-3.1 ng mL-1 in the luteal phase of the oestrous cycle: naloxone failed to increase LH concentrations. It is concluded that LH can be further suppressed by opiates given to cows during the negative feedback phase of oestradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Feedbacks and the coevolution of plants and atmospheric CO2.

The coupled evolution of land plants, CO2, and climate over the last half billion years has maintained atmospheric CO2 concentrations within finite limits, indicating the involvement of a complex network of geophysiological feedbacks. But insight into this important regulatory network is extremely limited. Here we present a systems analysis of the physiological and geochemical processes involved, identifying new positive and negative feedbacks between plants and CO2 on geological time scales. Positive feedbacks accelerated falling CO2 concentrations during the evolution and diversification of terrestrial ecosystems in the Paleozoic and enhanced rising CO2 concentrations across the Triassic-Jurassic boundary during flood basalt eruptions. The existence of positive feedbacks reveals the unexpected destabilizing influence of the biota in climate regulation that led to environmental modifications accelerating rates of terrestrial plant and animal evolution in the Paleozoic.

Biological Evolution↗

Somatosensory feedback modulates the respiratory motor program of crystallized birdsong.

Birdsong, like human speech, involves rapid, repetitive, or episodic motor patterns requiring precise coordination between respiratory, vocal organ, and vocal tract muscles. The song units or syllables of most adult songbirds exhibit a high degree of acoustic stereotypy that persists for days or months after the elimination of auditory feedback by deafening. Adult song is assumed to depend on central motor programs operating independently from immediate sensory feedback. Nothing is known, however, about the possible role of mechanoreceptive or other somatosensory feedback in the motor control of birdsong. Even in the case of human speech, the question of "how and when sensory information is used in normal speaking conditions...remains unanswered" and controversial [Smith, A. (1992) Crit. Rev. Oral Biol. Med. 3, 233-267]. We report here evidence for somatosensory modulation of ongoing song motor patterns. These patterns include the respiratory muscles that, in both birdsong and speech, provide the power for vocalization. Perturbing respiratory pressure by a brief, irregularly timed injection of air into the cranial thoracic air sac during song elicited a compensatory reduction in the electrical activity of the abdominal expiratory muscles, both in hearing and deafened adult northern cardinals (Cardinalis cardinalis). This muscle response was absent or reduced during quiet respiration, suggesting it is specifically linked to phonation. Our findings indicate that somatosensory feedback to expiratory muscles elicits compensatory adjustments that help stabilize, in real time, the subsyringeal pressure against fluctuations caused by changes in posture or physical activity.

Animals↗

Epigenetic properties of white-opaque switching in Candida albicans are based on a self-sustaining transcriptional feedback loop.

White-opaque switching in the human fungal pathogen Candida albicans is an alternation between two distinct types of cells, white and opaque. White and opaque cells differ in their appearance under the microscope, the genes they express, their mating behaviors, and the host tissues for which they are best suited. Each state is heritable for many generations, and switching between states occurs stochastically, at low frequency. In this article, we identify a master regulator of white-opaque switching (Wor1), and we show that this protein is a transcriptional regulator that is needed to both establish and maintain the opaque state. We show that in opaque cells, Wor1 forms a positive feedback loop: It binds its own DNA regulatory region and activates its own transcription leading to the accumulation of high levels of Wor1. We further show that this feedback loop is self-sustaining: Once activated, it persists for many generations. We propose that this Wor1 feedback loop accounts, at least in part, for the heritability of the opaque state. In contrast, white cells (and their descendents) lack appreciable levels of Wor1, and the feedback loop remains inactive. Thus, this simple model can account for both the heritability of the white and opaque states and the stochastic nature of the switching between them.

Candida albicans↗

cAMP-response elements in Aplysia creb1, creb2, and Ap-uch promoters: implications for feedback loops modulating long term memory.

The Aplysia genes encoding for cAMP-response element-binding protein 1 (CREB1), CREB2, and ubiquitin C-terminal hydrolase (Ap-uch) have been implicated in the formation of long term memory. However, nothing is known about the promoter regions of these genes or the transcription factors that regulate them. We cloned the promoter regions of creb1, creb2, and Ap-uch and identified a canonical cAMP-response element (CRE) in the promoter region of creb1. Variants of the canonical CRE were identified in all three promoters. TATA boxes and C/EBP-binding motifs are also present in the promoter regions of these genes. Promoter immunoprecipitation assays and chromatin immunoprecipitation assays indicated that CREB1 and CREB2 bind to the promoter regions of creb1 and creb2, suggesting that feedback loops modulate the formation of long term memory. In a positive feedback loop, phosphorylated CREB1 might induce its own gene via CREs. In support of this suggestion, treatment with serotonin enhanced binding of CREB1 to its promoter region and increased mRNA levels of creb1. Levels of Ap-uch mRNA also increased in response to serotonin; however, binding of CREB1 or CREB2 to the promoter region of Ap-uch was not detected. The finding that the promoter region of creb2 has a CRE raises the intriguing possibility that its expression is regulated by CREB1 and/or CREB2. CREB2 may repress its own gene, forming a negative feedback loop, and CREB2 up-regulation via CREB1 may limit the activity of the CREB1-mediated positive feedback loop.

Animals↗

A feedback-resistant mutant of Bacillus subtilis glutamine synthetase with pleiotropic defects in nitrogen-regulated gene expression.

The Bacillus subtilis TnrA transcription factor regulates gene expression during nitrogen-limited growth. When cells are grown with excess nitrogen, feedback-inhibited glutamine synthetase forms a protein-protein complex with TnrA and prevents TnrA from binding to DNA. A mutation in glutamine synthetase with a phenylalanine replacement at the Ser-186 residue (S186F) was isolated by screening for B. subtilis mutants with constitutive TnrA activity. Although S186F glutamine synthetase has kinetic properties that are similar to the wild-type protein, the S186F enzyme is resistant to feedback inhibition by glutamine and AMP. Ligand binding experiments revealed that the S186F protein had a lower affinity for glutamine and AMP than the wild-type enzyme. S186F glutamine synthetase was defective in its ability to block DNA binding by TnrA in vitro. The properties of the feedback-resistant S186F mutant support the model in which the feedback-inhibited form of glutamine synthetase regulates TnrA activity in vivo.

Adenosine Monophosphate↗

Visual influence on postural control, with and without visual motion feedback.

Body sway was investigated in 20 healthy subjects to determine whether visual input must contain motion feedback information from the surroundings in order to influence postural control. Posturography was used to record body sway under the following visual conditions: eyes open with or without a restricted visual field; eyes open in ganzfield white light; eyes open in darkness with a head-fixed visual target; eyes open in darkness; and eyes closed in darkness. Stance was perturbed by means of a pseudorandomly applied vibratory stimulation to the calf muscles. Least sway was found with eyes open in an unrestricted visual field but increased in a restricted visual field. Greatest sway was found without visual motion feedback, i.e. under the following conditions: eyes closed; eyes open in darkness; eyes open in ganzfield white light; and with a head-mounted fixation point. Sway was significantly (p < 0.05) greater with eyes open in darkness compared with eyes closed during the initial 50 s with perturbations. After 150 s, sway was almost identical under the four test conditions without visual motion feedback. Standing with eyes open in darkness was initially a disadvantage compared with having the eyes closed. The postural control system may be programmed to expect visual feedback information when the eyes are open, which may delay changes in postural strategy.

Adaptation, Physiological↗

A strategy for improving worker satisfaction and job attitudes in a repetitive industrial task: application of production standards and performance feedback.

Worker satisfaction improved significantly as a consequence of the provision of the assigned and participative standards with performance feedback in a repetitive industrial production task. The maximum improvement in worker satisfaction was found for the participative standard and feedback condition. Only this condition had a significant positive effect on worker job attitudes. Monetary incentive, when provided with an assigned or participative standard with feedback, added no incremental worker satisfaction or job attitudes gain. The participative standard with feedback condition emerges as the optimum strategy for improving worker satisfaction and job attitudes in a repetitive industrial production task.

Adult↗