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Results for “augmented feedback”

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PubMed1982

Lack of time-dependent augmentation of carotid sinus baroreflex system after vagotomy.

The purpose of this experiment was to study whether the carotid sinus baroreflex system (CS system) increases its gain with time after vagotomy in compensation for the loss of the vagally mediated arterial pressure control system (V system). In 7 dogs anesthetized with pentobarbital sodium we determined the responsiveness of the V system by repeatedly measuring the overall open-loop gain (G) of the negative feedback control system. G was assessed as (delta API/delta APS) -- 1, where delta API and delta APS are, respectively, the immediate and steady-state falls in arterial pressure at the aortic arch following a stepwise reduction in blood volume. delta API, delta APS, and G in intact condition were -12.0 +/- 1.8 mmHg, -1.1 +/- 0.2 mmHg, and 10.1 +/- 0.7 (SD), respectively. delta API, delta APS, and G after vagotomy, i.e., G of the CS system (GCS), were -15.6 +/- 3.6 mmHg, -6.4 +/- 1.9 mmHg, and 1.6 +/- 0.4 GCS did not change with time over 4 h after vagotomy. We conclude that the CS system cannot augment its ability to restore arterial pressure in compensation for the lost function of the V system within 4 h after vagotomy in the anesthetized dog.

Animals↗

PubMed1985

Lack of ovarian steroid negative feedback on pulsatile luteinizing hormone release between estrus and diestrous day 1 in the rat estrous cycle.

The object of this study was to determine the roles of ovarian estradiol (E2) and progesterone (P) in regulating pulsatile LH release between estrus and diestrous day 1 (D1) in the rat estrous cycle. Three groups of rats were bled at rates of 75 or 100 microliter whole blood/6 or 8 min, respectively, between 0930-1230 h on estrus or 24 h after either sham ovariectomy (OVX) on estrus (i.e. on D1) or OVX on estrus. There were no differences in plasma E2 and P levels in rats between estrus and early D1. However, after OVX on estrus, plasma levels of both steroids declined and were significantly lower 24 h later than values in D1 controls, indicating an active ovarian secretion of both hormones in this interval of the rat cycle. A significant increase in mean blood LH levels occurred between estrus and D1 due to an increase in LH pulse amplitude and frequency. After OVX on estrus, all parameters of pulsatile LH release also increased within 24 h, but mean blood LH levels as well as LH pulse amplitude and frequency were virtually identical to values in D1 controls, despite the decline in plasma E2 and P levels. Thus, OVX did not augment the increases in LH pulse amplitude and frequency that occur between estrus and D1. This demonstrates that the increase in pulsatile LH release from estrus to early D1 occurs in the absence of ovarian steroid negative feedback; the increases in LH pulse amplitude and frequency are not under negative feedback control by the low plasma levels of E2 and P present at this time. These data stand in direct contrast to the presence of prominent ovarian steroid negative feedback systems operative between D1 and diestrous day 2, and diestrous day 2 and proestrus.

Animals↗

PubMed2005

Suppressor of cytokine signaling 1 suppresses muscle differentiation through modulation of IGF-I receptor signal transduction.

Suppressor of cytokine signaling (SOCS) 1 was initially identified as an intracellular negative feedback regulator of the JAK-STAT signal pathway. Recently, it has been suggested that SOCS1 affects signals of growth factors and hormones. One of them, SOCS1, is also known to be involved in auto-regulation of IRS-1-mediated signaling. However, the mechanism(s) of SOCS1 induction by insulin-like growth factor (IGF)-I and a role of SOCS1 on IGF-I receptor-mediated signaling are not clarified. Here, we investigate SOCS1 on muscle differentiation. We found that muscle differentiation was suppressed in SOCS1 stable transformant C2C12 myoblasts, while it was promoted in SOCS1-deficient myoblasts. Additionally, SOCS1 augmented MEK phosphorylation and reduced Akt phosphorylation induced by IGF-I. Then, SOCS1 stable transformant C2C12 myoblasts, infected with adenovirus bearing constitutively active Akt, have the ability to differentiate again. Collectively, these findings suggest that SOCS1 suppresses muscle differentiation through negative feedback regulation of IGF-I receptor-mediated signaling.

Animals↗

PubMed2002

Sensory interactions for human balance control revealed by galvanic vestibular stimulation.

Many types of sensory information are known to contribute to the human balance control process but little is known about how the different sensory channels interact. Here we consider the postural response to a perturbation delivered to the vestibular channel using galvanic vestibular stimulation. We show that the response is modified by the absence of information in the other sensory channels. Removal of somatosensory information leads to a massive increase in response size. Similarly, removal of visual information augments the response. Furthermore, the response size is graded according to the amount of visual information available. These effects occur through two processes. One that influences the developing response through feedback mechanisms and another that influences the initial response selection through gain changes. The latter is described as a competitive process that can be likened to a proportional representation voting system.

Animals↗

PubMed1975

Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses.

Mice immunized with more SRBC than are required to produce optimal delayed-type hypersensitivity reactions, developed good antibody responses and poor delayed foot pad reactions. Cyclophosphamide treatment in low doses (20 mg/kg) before immunization, augmented the delayed-type hypersensitivity without affecting antibody responses. Cyclophosphamide did not augment delayed responses to optimal doses of SRBC (0.01%), but did augment the delayed hypersensitivity response of mice immunized with a suboptimal antigen dose (0.001%); which produced no detectable antibody response with or without cyclophosphamide pretreatment. These results suggest that antibody feedback is not the sole regulator of delayed reactions; the possibility that suppressor T cells may also be involved is discussed.

Animals↗

PubMed1989

A highly inducible system of gene expression by positive feedback production of glucocorticoid receptors.

To investigate the function of a cloned gene, inducible enhancer/promoters are preferred for controlling the level of expression experimentally. Highly inducible gene expression systems with both low basal levels and enhanced maximal levels of expression are especially sought. We have developed a new expression system using a positive feedback mechanism. Glucocorticoid receptor cDNA was fused to the enhancer/promoter of mouse mammary tumor virus (MTV) to induce receptor production. Simultaneous introduction of this receptor plasmid into mouse Ltk- cells augmented the expression of the reporter gene linked with the MTV enhancer/promoter by 10- to 100-fold in an induced state, but did not significantly change the expression of that in an uninduced state. This novel system of gene expression is a good candidate for an efficient genetic switch.

Animals↗

PubMed2004

Small-group videotape training for psychotherapy skills development.

OBJECTIVE: Psychotherapy instructors have used video technology to train residents for over 40 years. Though it has met with some controversy, many will argue that videotape review is essential for self-directed learning and accurate psychotherapy supervision. METHODS: The author describes a technique of small-group videotape training as provided in a psychiatry residency training program. RESULTS: He reviews the merits and limitations of this format and suggests simple and inexpensive technical approaches to augment this training. CONCLUSION: The author concludes that small-group videotape training is an efficient psychotherapy training format that encourages self-monitoring and the exchange of supportive peer feedback.

Clinical Competence↗

PubMed1989

Maturation and activation of hypothalamic-pituitary adrenal function in fetal sheep.

The progressive rise in the concentration of cortisol in the plasma of fetal sheep during late pregnancy arises from the sequential maturation of the fetal HPA axis. In addition, cortisol itself occupies a central role in accelerating this process through a series of feed-forward mechanisms. Before days 100-110 of pregnancy AVP appears to predominate over CRH as the major corticotropin-releasing factor in the fetus. Pituitary responsiveness to CRH increases progressively after day 100, and precedes maturation of fetal adrenal responsiveness to endogenous or exogenous ACTH. Cortisol accelerates the increase in the ratio of adult-fetal corticotropes in the fetal pituitary. In addition, cortisol modulates the mechanism by which ACTH activates fetal adrenal function, possibly through an action at the level of the ACTH receptor. Cortisol appears also to mediate the rise in fetal plasma CBG concentrations during late pregnancy, and may thereby alter the efficacy of the negative feedback process. In women, cortisol acts on the placenta to promote rather than to inhibit CRH output. CRH from the placenta may reach significant concentrations in the fetal circulation and augment the drive to fetal ACTH release. It may also act in a paracrine fashion to promote placental POMC gene expression. The importance of placental CRF and ACTH in the sheep is not yet apparent. These feed-forward loops establish a series of positive cascades that ensure concurrent rises in plasma ACTH and cortisol in the fetal circulation during late pregnancy. We suggest that this sequence leads to, and is broken by, the process of birth.

Adrenal Glands↗

PubMed1995

Activation and inhibition of the hypothalamic-pituitary-adrenal axis of the neonatal rat: effects of maternal deprivation.

These studies investigated the activation and inhibition (negative feedback) of the neonatal rat. The ACTH response of maternally deprived pups is persistently elevated for 30 min, suggesting a deficiency in the negative feedback system. In Experiment 1, we examined the time-course of corticosterone (CORT) and ACTH responses to a saline injection over a 120-min period during development. In deprived pups, CORT and ACTH were persistently elevated throughout the testing period, whereas only 15-day-old nondeprived pups showed ACTH and CORT elevations. Further nondeprived and deprived pups were exposed twice to ether (Experiment 2) or saline injections (Experiment 3) separated by a 1-h interval. Nondeprived pups showed an augmented ACTH response to double exposure to ether, but not to saline. No CORT response to either stimulus was observed. In response to one exposure of each stimulus, deprived pups showed increased ACTH and CORT values and no further elevation to repeated exposure. These results suggest the negative feedback system of neonates is immature, but partially functional in deprived pups. Moreover, nondeprived pups show a stressor-specific response to stress, whereas deprived animals show a similar response to different stimuli.

Adrenocorticotropic Hormone↗

PubMed2003

pH changes in the invaginating synaptic cleft mediate feedback from horizontal cells to cone photoreceptors by modulating Ca2+ channels.

Feedback from horizontal cells (HCs) to cone photoreceptors plays a key role in the center-surround-receptive field organization of retinal neurons. Recordings from cone photoreceptors in newt retinal slices were obtained by the whole-cell patch-clamp technique, using a superfusate containing a GABA antagonist (100 microM picrotoxin). Surround illumination of the receptive field increased the voltage-dependent calcium current (ICa) in the cones, and shifted the activation voltage of ICa to negative voltages. External alkalinization also increased cone ICa and shifted its activation voltage toward negative voltages. Enrichment of the pH buffering capacity of the extracellular solution increased cone ICa, and blocked any additional increase in cone ICa by surround illumination. Hyperpolarization of the HCs by a glutamate receptor antagonist-augmented cone ICa, whereas depolarization of the HCs by kainate suppressed cone ICa. From these results, we propose the hypothesis that pH changes in the synaptic clefts, which are intimately related to the membrane voltage of the HCs, mediate the feedback from the HCs to cone photoreceptors. The feedback mediated by pH changes in the synaptic cleft may serve as an additional mechanism for the center-surround organization of the receptive field in the outer retina.

Action Potentials↗

PubMed1981

Positive feedback effect of dihydrotestosterone on follicle-stimulating hormone secretion in the male rat: implications and a possible relation to the onset of puberty.

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were measured in serum of adult male rats after 6 days of constant subcutaneous infusion of varying levels of dihydrotestosterone (DHT). Doses from one-half up to the normal "blood production rate" of DHT produced a selective stimulation of serum FSH, but not LH, levels. Higher levels suppressed FSH, LH, and testosterone. Despite the presence of much higher levels of testosterone in blood, the augmentation of FSH secretion indicated in these studies suggests that DHT may have an important role in regulatory systems for gonadotropins.

Animals↗

PubMed2000

A possible role of soluble receptors to cell growth factors in body aging.

It is assumed that production by differentiated cells of soluble receptors to cell growth factors may mediate a feedback mechanism controlling cell growth and differentiation in the body. Based on this assumption, it is hypothesized that with age a concentration of such soluble receptors in the body fluids gradually augments as a consequence of increasing a proportion of the differentiated cell pool. In the old body, when present in the cellular microenvironment at relatively high concentrations these receptors might markedly diminish ligand binding to the membrane-bound counterparts in a competitive manner and, thereby, significantly reduce cell regeneration activity. Under such conditions, the niches forming because of cell death could be being filled by connective fibers rather than newly generated cells.

Aging↗

PubMed1997

Protein kinase A (PKA)- and protein kinase C-phosphorylated glia maturation factor promotes the catalytic activity of PKA.

We observed previously that glia maturation factor (GMF), a 17-kDa brain protein, is rapidly phosphorylated in astrocytes following stimulation by phorbol ester, and that protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regulated kinase (ERK) and enhancer of p38; both are subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascades. In the current report, we present evidence that PKA-phosphorylated GMF also promotes (11-fold) the catalytic activity of PKA itself, resulting in a positive feedback loop. Furthermore, GMF phosphorylated by protein kinase C (PKC), but not by casein kinase II or p90 ribosomal S6 kinase, also activates PKA (7-fold). It appears that the mutual augmentation of GMF and PKA, and the stimulating effect of PKC, both serve to maximize the influence of PKA on the regulation of MAP kinase cascades by GMF. Using synthetic peptide fragments containing putative phosphorylation sites of GMF, we demonstrate that PKA is capable of phosphorylating threonine 26 and serine 82, whereas PKC, p90 ribosomal S6 kinase, and casein kinase II, can phosphorylate serine 71, threonine 26, and serine 52, respectively. The generation of various phospho-isoforms of GMF may explain its modulation of signal transduction at multiple locations.

Amino Acid Sequence↗

PubMed1991

Increase in serum and bile cholesterol and HMG-CoA reductase by lovastatin in rats.

Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, is effective in the treatment of hypercholesterolemic patients and is currently being evaluated as a potential agent for dissolving gallstones. We therefore evaluated its effect on cholesterol metabolism in a rat model. A low-cholesterol diet containing 0.1% lovastatin was fed 15 h and 7 and 21 days. Microsomal HMG-CoA reductase activity, hepatic cholesterol synthesis, blood cholesterol, and biliary lipid output were determined and compared with control rats. Hepatic cholesterol synthesis increased ninefold after 7 days and levels of HMG-CoA reductase activity sevenfold. Biliary cholesterol excretion maximally increased fourfold. Biliary lipid output was still elevated after 21 days of treatment (cholesterol 3-fold and phospholipid 2-fold, P less than 0.01). Bile salt output did not change. Augmented responses to lovastatin were present but less on the high-cholesterol diet. The data are consistent with the hypothesis that lovastatin increases HMG-CoA reductase activity through a feedback mechanism that promoted increased cholesterol synthesis, biliary lipid secretion, and elevated blood cholesterol. There was an apparent coupling of biliary cholesterol output with phospholipids but not with bile salts. Although lovastatin also increased microsomal HMG-CoA reductase activity in humans, cholesterol synthesis is not stimulated but is inhibited. This may be explained by higher permeability of the microsomal membranes for lovastatin. Thus the effect of HMG-CoA reductase inhibitors on cholesterol synthesis in different species should then depend on the properties of microsomal membranes.

Animals↗

PubMed1997

Neuroendocrine mechanisms by which selective Leydig cell castration unleashes increased pulsatile LH release.

A novel pharmacological model of acute reversible Leydig cell "castration" induced by a steroidogenic enzyme inhibitor, ketoconazole, achieves marked hypoandrogenemia in healthy men with an attendant 2.5-fold increase in 24-h mean serum luteinizing hormone (LH) concentrations. Mechanistically, the unleashing of amplified pulsatile LH release can be accounted for by any of three distinct models of deconvolution-estimated gonadotropin secretion, all of which are marked by a nearly twofold acceleration in LH secretory burst frequency. In addition, the models variously also predict concomitant prolongation of the endogenous LH half-life, an augmented LH secretory burst mass and duration, and/or the emergence of significant basal LH secretion. The nyctohemeral (cosinor analysis) rhythmicity of serum LH concentrations is not disturbed when androgenic negative-feedback signaling is withdrawn abruptly, but the apparent process randomness of LH release increases, as quantified by higher approximate entropy values. Thus we conclude that an intact (closed loop) androgen-mediated negative-feedback network in the adult human male is required to sustain low-frequency pulsatile LH release in a quantifiably orderly manner.

Adolescent↗

PubMed2003

Heart rate variability in athletes.

This review examines the influence on heart rate variability (HRV) indices in athletes from training status, different types of exercise training, sex and ageing, presented from both cross-sectional and longitudinal studies. The predictability of HRV in over-training, athletic condition and athletic performance is also included. Finally, some recommendations concerning the application of HRV methods in athletes are made.The cardiovascular system is mostly controlled by autonomic regulation through the activity of sympathetic and parasympathetic pathways of the autonomic nervous system. Analysis of HRV permits insight in this control mechanism. It can easily be determined from ECG recordings, resulting in time series (RR-intervals) that are usually analysed in time and frequency domains. As a first approach, it can be assumed that power in different frequency bands corresponds to activity of sympathetic (0.04-0.15 Hz) and parasympathetic (0.15-0.4 Hz) nerves. However, other mechanisms (and feedback loops) are also at work, especially in the low frequency band. During dynamic exercise, it is generally assumed that heart rate increases due to both a parasympathetic withdrawal and an augmented sympathetic activity. However, because some authors disagree with the former statement and the fact that during exercise there is also a technical problem related to the non-stationary signals, a critical look at interpretation of results is needed. It is strongly suggested that, when presenting reports on HRV studies related to exercise physiology in general or concerned with athletes, a detailed description should be provided on analysis methods, as well as concerning population, and training schedule, intensity and duration. Most studies concern relatively small numbers of study participants, diminishing the power of statistics. Therefore, multicentre studies would be preferable. In order to further develop this fascinating research field, we advocate prospective, randomised, controlled, long-term studies using validated measurement methods. Finally, there is a strong need for basic research on the nature of the control and regulating mechanism exerted by the autonomic nervous system on cardiovascular function in athletes, preferably with a multidisciplinary approach between cardiologists, exercise physiologists, pulmonary physiologists, coaches and biomedical engineers.

Autonomic Nervous System↗

PubMed1995

Isovelocity investigation of the lengthening behaviour of the erector spinae muscles.

The purpose of this study was to investigate the force-velocity (F/v) relationship for the erector spinae muscles in submaximal activation movements, with particular attention to their response during lengthening movements and at lower shortening contraction velocities. Dynamic models that predict lower back muscle forces require reasonable representations of the modulating effect of instantaneous velocity. Ten males were observed performing trunk flexion and extension in the sagittal plane under constant load. Contraction velocities were measured as the first derivative from a devise sensitive to changes in spine curvature, and controlled by a visual feedback system while a constant load was applied through a chest harness. The erector spinae exhibited a yielding phenomenon which causes an abrupt drop in force during constant velocity stretching under constant, submaximal, stimulation. The findings were consistent with previous isovelocity muscle lengthening experiments. Yielding appeared dependent on the level of load/activation supporting the theory of a "state-variable" F/v relationship. The eccentric behaviour of the lower erectors (L3) seemed independent of velocity and length, while that of the upper erectors (T9) showed a dependence on length. At lower concentric velocities, concavity in torque-velocity curves was noted after a "threshold" velocity. The findings of this study strongly reinforce the notion that the F/v length relationship is not a continuous hyperbolic relationship during muscle shortening and that the commonly modelled force augmentation effect of lengthening is incorrect, at least for submaximal activation of the extensors of the lower back.

Adult↗

PubMed2002

HEAL: an instructional design model applied to an online clerkship in family medicine.

OBJECTIVE: The potential of distance learning technology to deliver educational programs in which instruction and evaluation are of a consistent and high standard across multiple settings is hampered by a lack of instructional design models. In response, we developed the HEAL (Heuristic for Electronic Asynchronous Learning) model for designing online curricula. DESCRIPTION: HEAL is based on the theories that learning is facilitated by independent problem solving, investigation, and discovery (heuristics); collaboration between students fosters learning; and the proven educational cycle of practice, feedback, and reflection is integral to the interrelated domains of skill development and personal awareness.(1) The HEAL model is defined by synergistic online learning activities integrated with real patient care. It is applicable to all medical education levels. We applied this innovative design template to an online curriculum that augments our conventional six-week third-year clerkship. Our students, who were placed in distant family physician offices, needed more interaction and learning from peers and faculty. The three elements of HEAL, and implementation in the "online clerkship," are: (1) Didactic modules teach and illustrate concepts. Students study modules (HTML pages) on management of diabetes (DM), and complete five modules on evidence-based medicine (EBM). They do EBM literature searches reviewed online by peers, faculty, and librarians, who provide feedback. (2) A problem-based case discussion promotes application of concepts from modules (horizontal curricular integration). Students view streamed video of a patient with a history suggestive of diabetes, review her medical chart online, and suggest evidence-based management in an asynchronous discussion group. The case progresses weekly to mimic 12 months of continuity of care. (3) A collaborative journal activity explores the results of applying elements one and two to real patients (vertical integration). Additional elements advance reflection, professionalism, and medical humanism. Participation in the journal discussion group, stimulated by online readings, enhances self-awareness, informs psychosocial aspects of element 2, and promotes generalization of learning objectives to real patients. We use BlackBoard software. Students log in two to three times per week. Faculty who are trained in online moderation facilitate the threaded discussion groups and provide feedback. DISCUSSION: Students in alternating clerkship blocks complete the online clerkship. Their performance is compared with that of students who complete a face-to-face diabetes curriculum, but no curriculum on EBM or medical humanism. After nearly a year (105 students), compared with the non-online group, students completing the online clerkship demonstrated greater gains in reported EBM skills from preto post-clerkship, larger increases in mean score (from pre to post) on a medical-humanism aptitude scale, and higher scores on a post-clerkship diabetes management assessment (all comparisons p <.05). The online clerkship will become a permanent part of our clerkship and we have begun to use HEAL to design other online courses, including continuing education courses.

Clinical Clerkship↗