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PubMedDate not supplied

The effect of psychotropic drugs on the interaction of protein kinase C with second messenger systems in the rat cerebral cortex.

The paper describes and compares the influences of the antidepressants (imipramine, mianserin, citalopram), electroconvulsive shock, and the neuroleptics (haloperidol, chlorpromazine and spiperone) on the systems of second messengers related to adrenergic receptors in rat cerebral cortex, measured by generation of cyclic AMP and inositol phosphate (IP), and their influence on the effects of activation of protein kinase C (PKC) by its synthetic activator, phorbol ester (TPA). The effect of PKC-stimulation was expressed as a reduction of noradrenaline-stimulated IP accumulation and, on the other hand, as an enhancement of cyclic AMP response under stimulation with noradrenaline and isoproterenol. When administered chronically, the described antidepressants (unlike the neuroleptics) augmented IP accumulation or left it unchanged, but they reduced PKC's negative feedback with the alpha 1-adrenoceptor. PKC-induced potentiation of cyclic AMP's response to beta-adrenergic receptor stimulation was unchanged or enhanced, while the antidepressants reduced the generation of this second messenger. However, citalopram increased cyclic AMP generation and reduced PKC potentiation. Taking into account the role of PKC in adrenergic receptors cross-talk explains why, despite antagonization of alpha 1-adrenoceptors and induction of beta down-regulation by some antidepressants, enhancement of the process of noradrenergic neurotransmission can occur as a final effect of the action of these drugs. It was found that the action of antidepressants is largely related to the adrenergic system, even when their action on this system is not direct and is accomplished by their influence on another neurotransmitting system, e.g. the serotonergic system.

Animals↗

PubMed1983

Evidence of prolactin short loop feedback in the postpartum lactating rat.

Serum prolactin was studied in lactating and nonlactating rats after restraint stress, chronic estradiol benzoate treatment, and acute L-tryptophan treatment. As expected, these treatments evoked increases in serum prolactin in nonlactating rats. In lactating rats these treatments did not increase basal serum prolactin when litters were removed for 4 hr. Daily estradiol benzoate treatment increased pituitary gland prolactin content after 14 days, but there was no effect on basal serum prolactin. Daily estradiol treatment did not augment prolactin release in response to 30 min of suckling. It is suggested that the short loop feedback by prolactin (i.e., prolactin inhibiting its own secretion) makes the lactating rat refractory to these stimuli of prolactin secretion.

Animals↗

PubMed1991

Methodology for motor learning: a paradigm for kinematic feedback.

Knowledge of results (KR)--information feedback about goal achievement--has been one of the most extensively examined variables in motor learning. In most natural movement learning situations, however, instructors more common]y provide augmented information regarding various kinematic or kinetic aspects of the movement pattern itself (sometimes termed knowledge of performance, KP). But despite the inherent interest in kinematic feedback, several factors reviewed here have operated to inhibit its study, the most important of which has been the lack of a suitable laboratory task and paradigm. The limitations of earlier paradigms have concerned (a) the use of overly simple motor behaviors, probably to minimize the problems in kinematic measurement, (b) the tendency for the environmental goal or the task to be isomorphic with the kinematic pattern, and (c) thc failure to use transfer or retention tests as measures of learning effects of the feedback manipulations. In this article, we describe our efforts to create a new paradigm for kinematic feedback, the rationale for its development, and the details of its operation. Finally, we provide evidence that the task and paradigm are sensitive to manipulations of kinematic feedback, providing some assurance that the paradigm can potentially answer future research questions about the role of kinematic feedback for learning.

Journal Article↗

PubMed1975

Time course of changes in plasma renin after blockade of the renin-system. Studies of conscious and anaesthetized, normal, adrenalectomized and spontaneously hypertensive rats.

Inhibition of the angiotensin I converting enzyme with SQ 20.881 results in a 2 to 35 fold increase in plasma renin concentration in normal rats and in spontaneously hypertensive rats. The effect is transient, lasting for 1 to 3 hours even in the presence of prolonged blockade. The relative increase is independent of the pretreatment plasma renin concentration. The blood pressure is unchanged in conscious rats in which the effect of SQ 20.881 on plasma renin is believed to be due to a blockade of the negative feedback of angiotensin II on renin release. In anaesthetized rats, SQ 20.88) has an additional hypotensive effect which augments the increase in plasma renin. Saralasin is without effect on blood pressure and plasma renin in conscious normal rats and in spontaneously hypertensive rats, while it causes a transient 3 to 27 fold increase in plasma renin concentration in anaesthetized rats. It is suggested that this increase is hardly due to an interception of the feedback, but to the concomitant fall in blood pressure, as a similar hypotension and increase in plasma renin is produced by dihydralazine. It is furthermore found that Saralasin blocks renin release induced by SQ 20.881. This demonstrates that Saralasin is bound to the receptors in the juxtaglomerular cells and has slight, agonistic properties there. Both in conscious rats and in anaesthetized adrenalectomized rats substituted with DOCA and salt, SQ 20.881 as well Saralasin causes transient increases in plasma renin concentration. If such rats are only substituted with salt and not with DOCA, the effects of both blockers are in the form of severe hypotension and a permanent elevation of plasma renin.

Adrenalectomy↗

PubMed1982

Endotoxin-stimulated opioid peptide secretion: two secretory pools and feedback control in vivo.

Small doses of endotoxin evoked a dramatic biphasic response of opioid peptide secretion into blood in sheep. The first phase began within minutes and coincided with a brief hypertensive response to endotoxin well before the appearance of fever or hypotension. The ratio of beta-endorphin to beta-lipotropin fell abruptly at the onset of the second phase of release, suggesting early depletion of a pool rich in beta-endorphin and subsequent emergence of a pool rich in unprocessed precursor. The concentration of cerebrospinal fluid opioids increased tenfold during the second phase. Naloxone administration augmented endotoxin-induced opioid secretion in both early and late phases, suggesting a short-loop feedback regulation of stress-induced endorphin secretion.

Animals↗

PubMed2000

Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent.

Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. We investigated whether supplementation of nine apparently healthy vegans with 2.01 g ALA (4 ml linseed oil), 1.17 g gamma-linolenic acid (GLA) (6 ml borage oil) or their combination increases the LCP omega 3 contents of erythrocytes (RBC) and platelets (PLT), and of plasma phospholipids (PL), cholesterol esters (CE) and triglycerides (TG). The supplements changed the dietary LA/ALA ratio (in g/g) from about 13.7 (baseline) to 6.8 (linseed oil), 14.3 (borage oil) and 6.4 (linseed + borage oil), respectively. ALA or GLA given as single supplements did not increase LCP omega 3 status, but their combination augmented LCP omega 3 (in CE) and EPA (in fasting TG) to a statistically significant, but nevertheless negligible, extent. We conclude that negative feedback inhibition by dietary LCP, if any, does not play an important role in the inability to augment notably DHA status by dietary ALA. The reach of a DHA plateau already at low dietary ALA intakes suggests that dietary DHA causes a non-functional DHA surplus, or is, alternatively, important for maintaining DHA status at a functionally relevant level.

Adult↗

PubMed1995

On the interaction of prior knowledge and stimulus structure in category learning.

Contemporary theories of categorization propose that concepts are coherent in virtue of being embedded in a network of theories about the world. Those theories function to pick out some of the many possible features of a set of objects as most salient for purposes of classification, a process that is complex and still poorly understood (Murphy & Medin, 1985). Part of what makes this account incomplete is a lack of information as to (1) what makes a feature salient on a given occasion and (2) how feature salience interacts with category structure to determine the course of learning. We report on the results of three studies of category learning using complex schematic drawings to show that (1) the contrast set defined by one's initial encounters with category exemplars can be a source of individual differences in feature salience assignments; (2) such effects are short-lived in the face of clear evidence about actual feature diagnosticity; and (3) more robust prior hypotheses interact with category structure to either enhance learning or impede it. The enhancement occurs when the hypothesis emphasizes category-relevant features, even if the hypothesis is in fact incorrect. A hypothesis that assigns high salience to irrelevant features impedes learning. Learning does occur as feedback concerning category structure leads to enhanced salience for relevant features. Salience of irrelevant features remains high, however, suggesting that such learning as occurs involves augmentation and not total revision of the (incorrect) prior hypothesis.

Attention↗

PubMed1989

Insight into the transfer function, gain, and oscillation onset for the pupil light reflex using nonlinear delay-differential equations.

Analogies are drawn between a physiologically relevant nonlinear delay-differential equation (DDE) model for the pupil light reflex and servo control analytic approaches. This DDE is shown to be consistent with the measured open loop transfer function and hence physiological insight can be obtained into the gain of the reflex and its properties. A Hopf bifurcation analysis of the DDE shows that a limit cycle oscillation in pupil area occurs when the first mode of the characteristic equation becomes unstable. Its period agrees well with experimental measurements. Beyond the point of instability onset, more modes become unstable corresponding to multiple encirclings of (-1, 0) on the Nyquist plot. These modes primarily influence the shape of the oscillation. Techniques from dynamical systems theory, e.g. bifurcation analysis, can augment servo control analytic methods for the study of oscillations produced by nonlinear neural feedback mechanisms.

Blinking↗

PubMed2006

Ethnographically informed community evaluation: a framework and approach for evaluating community-based initiatives.

OBJECTIVES: This paper describes ethnographically informed community evaluation (EICE), a framework for evaluating complex community-based interventions, and illustrates its use in the evaluation of Baltimore City Healthy Start, a federally funded infant mortality prevention project. EICE, which is influenced by cultural anthropology and assets-based community assessment, supports continuous program improvement, resident involvement, and measurement of community-level change. This approach takes into account both individual and contextual levels of analysis. METHODS: The evaluation coupled a participatory approach with qualitative and survey research methods to study community context and how it might contribute to infant mortality and influence program implementation, and to assess community change resulting from the program. Data collection included focus groups, key informant interviews, surveys, neighborhood mapping, journaling, and a study of community problem-solving. RESULTS: The evaluation provided program-related feedback to staff, contributed to a collective understanding of the local context, validated and augmented outcome findings, and imparted skills and a sense of empowerment to the neighborhood. Results reveal a community burdened by crime and social problems, yet showing great diversity in physical and social conditions when examined at the census block group level. Nevertheless, these social and physical hazards in the community are more salient than any specific health issue such as infant mortality. CONCLUSIONS: EICE is a powerful evaluation approach able to respond to the complexities of community-based maternal and child health initiatives designed to institute changes across multiple domains. EICE may be used, in whole or in part, as a supplement to traditional designs.

Anthropology, Cultural↗

PubMed2006

Synthesis, structure and properties of metal nanoclusters.

Metal nanoclusters have physical properties differing significantly from their bulk counterparts. Metallic properties such as delocalization of electrons in bulk metals which imbue them with high electrical and thermal conductivity, light reflectivity and mechanical ductility may be wholly or partially absent in metal nanoclusters, while new properties develop. We review modern synthetic methods used to form metal nanoclusters. The focus of this critical review is solution based chemical synthesis methods which produce fully dispersed clusters. Control of cluster size and surface chemistry using inverse micelles is emphasized. Two classes of metals are discussed, transition metals such as Au and Pt, and base metals such as Co, Fe and Ni. The optical and catalytic properties of the former are discussed and the magnetic properties of the latter are given as examples of unexpected new size-dependent properties of nanoclusters. We show how classical surface science methods of characterization augmented by chemical analysis methods such as liquid chromatography can be used to provide feedback for improvements in synthetic protocols. Characterization of metal clusters by their optical, catalytic, or magnetic behavior also provides insights leading to improvements in synthetic methods. The collective physical properties of closely interacting clusters are reviewed followed by speculation on future technical applications of clusters. (125 references).

Journal Article↗

PubMed1998

Regulation of cytokine expression by an autoreactive B cell clone derived from MRL/MP-lpr/lpr mice.

The B cell line, MRL159.5, was established by somatic hybridization between splenic MRL/MP-lpr/lpr (lpr) mice B cells and 2.52M, a hypoxanthine-aminopterine-thymidine (HAT) medium-sensitive B cell line mutant. It possessed a receptor molecule for mouse erythrocytes treated with bromelain (Br-MRBC) on its surface, likely to be an autoreactive B cell clone specific for Br-MRBC as detected by rosette-forming assay with Br-MRBC. MRL159.5 spontaneously produced IL-6 and secreted IgM, and was induced to augment IgM secretion when treated with Br-MRBC or IL-6. Triggering of CD40 led to an augmentation of IgM secretion as well as IL-6 expression. Blocking the binding of IL-6 to its cellular receptor through the use of inhibitory antibodies inhibited CD40-induced IgM secretion, suggesting a possible autocrine role of IL-6 for CD40-induced differentiation of this B cell hybridoma. Addition of IL-4 or Br-MRBC augmented IL-6 expression as well as IgM secretion by CD40-activated MRL159.5 cells. CD40 also augmented tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression but resulted in decreased IL-10 expression. Furthermore, under conditions where IL-6 expression was augmented, IL-6R alpha (gp80) expression was down-regulated, suggesting a negative feedback mechanism of an IL-6 autocrine loop in this hybridoma. These results demonstrate a role by which T cell-dependent activation through CD40 regulates an IL-6 autocrine loop, controlling differentiation of autoreactive B cells in autoimmune disease.

Animals↗

PubMed1997

Virtual reality therapy of multiple sclerosis and spinal cord injury: design consideration for a haptic-visual interface.

Multiple sclerosis and spinal cord injury patients can benefit by interaction with a haptic-visual system to increase the accuracy of movements in cases of spasticity, cerebellar tremor, and weakness. The device would apply a counterforce to constrain the upper extremity to a force corridor, a region of force/velocity space, designed to increase movement accuracy. Execution of movements with counterforce assistance under certain conditions improves accuracy and should enable patients to develop enhanced strategies for dealing with the movement disorders resulting from their neurologic deficits. Generation of appropriate force feedback requires dynamic adjustment of feedback plant characteristics and integration of visuospatial information in a virtual reality environment. Sensory augmentation, including compensation for visual and proprioceptive loss, can theoretically also be achieved with this approach. The underlying principles in the development of such a system are presented.

Computer Graphics↗

PubMed1998

Interactions between global motion and local binocular rivalry.

Binocular rivalry is thought to arise from a low-level cortical site. Experiment 1 evaluates this claim with respect to local and global motion processing by using a multiple-aperture motion stimulus and measuring the predominance of global coherence while one of the component gratings is engaged in rivalry. Results show that rivalry suppression of the component grating precludes global coherence. Presumable, suppression prevents the component motion signal from advancing to higher-level global motion areas, suggesting rivalry occurs between local and global motion processing. However, feedback from higher-level mechanisms might exert an influence on binocular rivalry and thus Experiment 2 measures how the predominance of a local target engaged in binocular rivalry with a competing local stimulus is affected when the target forms part of a globally coherent motion stimulus. The augmented level of target predominance during global motion relative to local motion indicates that higher-level motion mechanisms can feedback and influence the binocular rivalry process. Together, these data imply a looping hierarchy of motion processing stages, with rivalry suppression transpiring at an intermediate level and subject to feedback from higher-level motion areas.

Humans↗

PubMed2001

Mechanoelectrical feedback: role of beta-adrenergic receptor activation in mediating load-dependent shortening of ventricular action potential and refractoriness.

BACKGROUND: Augmented preload increases myocardial excitability by shortening action potential duration (APD). The mechanism governing this phenomenon is unknown. Because myocardial stretch increases intracellular cAMP, we hypothesized that load-dependent changes in myocardial excitability are mediated by beta-adrenergic stimulation of a cAMP-sensitive K(+) current. METHODS AND RESULTS: The effects of propranolol on load-induced changes in electrical excitability were studied in 7 isolated ejecting canine hearts. LV monophasic APD at 50% and 90% repolarization (MAPD(50) and MAPD(90)) and refractoriness were determined at low (9+/-3 mL) and high (39+/-4 mL) load before and after beta-adrenergic blockade. During control, the MAPD(50) decreased from 193+/-26 to 184+/-26 ms with increased load, as did the MAPD(90) (238+/-28 to 233+/-28 ms), P</=0.04. Similar changes were observed in ventricular refractoriness. Treatment with propranolol completely abolished these load-induced effects. Myocardial catecholamine depletion with reserpine in 2 hearts also abolished changes in MAPD and excitability in response to increased preload. CONCLUSIONS: Increases in ventricular load mediate a decrease in ventricular APD and refractoriness through activation of the beta-adrenergic receptor. An increase in a cAMP-mediated K(+) current, possibly the slowly activating delayed rectifier I(Ks), may account in part for this form of mechanoelectrical coupling.

Action Potentials↗

PubMed2002

Schema design and implementation of the grasp-related mirror neuron system.

Mirror neurons within a monkey's premotor area F5 fire not only when the monkey performs a certain class of actions but also when the monkey observes another monkey (or the experimenter) perform a similar action. It has thus been argued that these neurons are crucial for understanding of actions by others. We offer the hand-state hypothesis as a new explanation of the evolution of this capability: the basic functionality of the F5 mirror system is to elaborate the appropriate feedback - what we call the hand state - for opposition-space based control of manual grasping of an object. Given this functionality, the social role of the F5 mirror system in understanding the actions of others may be seen as an exaptation gained by generalizing from one's own hand to an other's hand. In other words, mirror neurons first evolved to augment the "canonical" F5 neurons (active during self-movement based on observation of an object) by providing visual feedback on "hand state," relating the shape of the hand to the shape of the object. We then introduce the MNS1 (mirror neuron system 1) model of F5 and related brain regions. The existing Fagg-Arbib-Rizzolatti-Sakata model represents circuitry for visually guided grasping of objects, linking the anterior intraparietal area (AIP) with F5 canonical neurons. The MNS1 model extends the AIP visual pathway by also modeling pathways, directed toward F5 mirror neurons, which match arm-hand trajectories to the affordances and location of a potential target object. We present the basic schemas for the MNS1 model, then aggregate them into three "grand schemas" - visual analysis of hand state, reach and grasp, and the core mirror circuit - for each of which we present a useful implementation (a non-neural visual processing system, a multijoint 3-D kinematics simulator, and a learning neural network, respectively). With this implementation we show how the mirror system may learn to recognize actions already in the repertoire of the F5 canonical neurons. We show that the connectivity pattern of mirror neuron circuitry can be established through training, and that the resultant network can exhibit a range of novel, physiologically interesting behaviors during the process of action recognition. We train the system on the basis of final grasp but then observe the whole time course of mirror neuron activity, yielding predictions for neurophysiological experiments under conditions of spatial perturbation, altered kinematics, and ambiguous grasp execution which highlight the importance of the timing of mirror neuron activity.

Animals↗

PubMed1999

Effect of basic fibroblast growth factor on gastric ulcer healing and its own mRNA expression.

BACKGROUND: The application of an acid-stable mutein of basic fibroblast growth factor (bFGF) called CS23 results in acceleration of ulcer healing. The modes by which this cytokine exerts these effects are not yet completely understood. AIM: To describe the pattern of bFGF-mRNA expression during ulcer healing and to examine the effects of exogenously applied CS23 on gastric ulcer healing in an animal model. METHODS: The speed of healing of gastric ulcers, expression of extracellular matrix gene mRNAs such as pro alpha(I) collagen (by non-radioactive in situ hybridization), cellular proliferation evidenced by the display of PCNA (by immunohistochemistry), angiogenesis, and the feedback of this growth factor on its own mRNA expression pattern were used to evaluate the effects of CS23 on rat gastric ulcer healing in an animal model. RESULTS: CS23 accelerates gastric ulcer healing at 7, 14 and 21 days after ulcer induction. We found an increase in connective tissue beneath the ulcer bed in treated animals in comparison to controls. The expression of PCNA as well as pro alpha(I) collagen mRNA was markedly increased in ulcers, yet there was no distinct difference between treatment arms. In contrast, the density of microvessels was significantly increased in the submucosa of ulcers by CS23 application. bFGF-mRNA expression is up-regulated in the submucosa during early ulcer healing; this increase diminishes within days but can be restituted by the exogenous application of CS23. CONCLUSIONS: CS23 speeds gastric ulcer healing and significantly increases the density of microvessels in the ulcerated tissue without affecting the numbers of proliferating cells or the transcription of collagen mRNA. In addition, it augments the expression of bFGF-mRNA during the later stages of healing, suggesting a positive feedback loop.

Animals↗

PubMedDate not supplied

Is obesity an inflammatory condition?

Obesity may be a low-grade systemic inflammatory disease. Overweight and obese children and adults have elevated serum levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and leptin, which are known markers of inflammation and closely associated with cardiovascular risk factors and cardiovascular and non-cardiovascular causes of death. This may explain the increased risk of diabetes, heart disease, and many other chronic diseases in the obese. The complex interaction between several neurotransmitters such as dopamine, serotonin, neuropeptide Y, leptin, acetylcholine, melanin-concentrating hormone, ghrelin, nitric oxide, and cytokines and insulin and insulin receptors in the brain ultimately determines and regulates food intake. Breast-feeding of more than 12 mo is associated with decreased incidence of obesity. Breast milk is a rich source of long-chain polyunsaturated fatty acids (LCPUFAs) and brain is especially rich in these fatty acids. LCPUFAs inhibit the production of proinflammatory cytokines and enhance the number of insulin receptors in various tissues and the actions of insulin and several neurotransmitters. LCPUFAs may enhance the production of bone morphogenetic proteins, which participate in neurogenesis, so these fatty acids might play an important role in brain development and function. It is proposed that obesity is a result of inadequate breast feeding, which results in marginal deficiency of LCPUFAs during the critical stages of brain development. This results in an imbalance in the structure, function, and feedback loops among various neurotransmitters and their receptors, which ultimately leads to a decrease in the number of dopamine and insulin receptors in the brain. Hence, promoting prolonged breast feeding may decrease the prevalence of obesity. Exercise enhances parasympathetic tone, promotes antiinflammation, and augments brain acetylcholine and dopamine levels, events that suppress appetite. Acetylcholine and insulin inhibit the production of proinflammatory cytokines and provide a negative feedback loop for postprandial inhibition of food intake, in part, by regulating leptin action. Statins, peroxisome proliferator-activated receptor-gamma binding agents, non-steroidal antiinflammatory drugs, and infant formulas supplemented with LCPUFAs, and LCPUFAs themselves, which suppress inflammation, may be beneficial in obesity.

Adult↗

PubMed2001

Phagocytosis of apoptotic inflammatory cells by microglia and modulation by different cytokines: mechanism for removal of apoptotic cells in the inflamed nervous system.

Apoptosis of autoaggressive T cells in the central nervous system (CNS) is an effective, nonphlogistic mechanism for the termination of autoimmune inflammation in experimental autoimmune encephalomyelitis (EAE). The clearance of apoptotic leukocytes by tissue-specific phagocytes is a critical event in the resolution of the inflammatory attack. To investigate the role of microglia in the removal of apoptotic cells and potential regulatory mechanisms of microglial phagocytosis, an in vitro phagocytosis assay was established, using Lewis rat microglia. Microglia exhibited a high capacity for the uptake of apoptotic autologous thymocytes, as well as apoptotic encephalitogenic myelin basic protein (MBP)-specific T cells, in contrast to nonapoptotic target cells. Pretreatment of microglia with interferon-gamma (IFN-gamma) raised the proportion of microglia capable of phagocytosing apoptotic cells to 75% above the untreated controls. The increased phagocytic activity was selective for apoptotic target cells and was not dependent on phosphatidylserine-mediated recognition mechanisms. In contrast, preincubation of microglia with interleukin-4 (IL-4) inhibited the uptake of apoptotic cells, whereas tumor-necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) did not alter phagocytosis. Phagocytic clearance of apoptotic inflammatory cells by microglia may be an important mechanism for the termination of autoimmune inflammation in the CNS. Augmentation of microglial phagocytosis by the Th-1-type cytokine IFN-gamma suggests a feedback mechanism for the accelerated clearance of the inflammatory infiltrate in the CNS.

Animals↗