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At least 631 records · Page 35Linked to original sources
PubMed1998

Identification of differentially expressed mRNA in prokaryotic organisms by customized amplification libraries (DECAL): the effect of isoniazid on gene expression in Mycobacterium tuberculosis.

Understanding the effects of the external environment on bacterial gene expression can provide valuable insights into an array of cellular mechanisms including pathogenesis, drug resistance, and, in the case of Mycobacterium tuberculosis, latency. Because of the absence of poly(A)+ mRNA in prokaryotic organisms, studies of differential gene expression currently must be performed either with large amounts of total RNA or rely on amplification techniques that can alter the proportional representation of individual mRNA sequences. We have developed an approach to study differences in bacterial mRNA expression that enables amplification by the PCR of a complex mixture of cDNA sequences in a reproducible manner that obviates the confounding effects of selected highly expressed sequences, e.g., ribosomal RNA. Differential expression using customized amplification libraries (DECAL) uses a library of amplifiable genomic sequences to convert total cellular RNA into an amplified probe for gene expression screens. DECAL can detect 4-fold differences in the mRNA levels of rare sequences and can be performed on as little as 10 ng of total RNA. DECAL was used to investigate the in vitro effect of the antibiotic isoniazid on M. tuberculosis, and three previously uncharacterized isoniazid-induced genes, iniA, iniB, and iniC, were identified. The iniB gene has homology to cell wall proteins, and iniA contains a phosphopantetheine attachment site motif suggestive of an acyl carrier protein. The iniA gene is also induced by the antibiotic ethambutol, an agent that inhibits cell wall biosynthesis by a mechanism that is distinct from isoniazid. The DECAL method offers a powerful new tool for the study of differential gene expression.

Base Sequence↗
PubMed1997

Internal objects--a theoretical analysis of Jungian and Kleinian models.

In this paper I discuss the ways in which experimental and objective research from cognitive science and developmental psychology can help analysts evaluate the theoretical models of mental objects which we use; I indicate the ways in which such evidence tends to support models of internal objects as mental representations or developmental capacities rather than as wish-fulfilling expressions of instinctual drives. This kind of empirical evidence is not just of academic interest but also has direct clinical relevance, particularly with borderline patients; such patients' sense of identity is totally dependent on the analyst's understanding of their internal world and for this to be misunderstood by the analyst can be catastrophic. An accurate theoretical model of mental objects can therefore help analysts to contain their patients more effectively.

Adult↗
PubMed2005

Trunk stiffness and dynamics during active extension exertions.

Spinal stability is related to the recruitment and control of active muscle stiffness. Stochastic system identification techniques were used to calculate the effective stiffness and dynamics of the trunk during active trunk extension exertions. Twenty-one healthy adult subjects (10 males, 11 females) wore a harness with a cable attached to a servomotor such that isotonic flexion preloads of 100, 135, and 170 N were applied at the T10 level of the trunk. A pseudorandom stochastic force sequence (bandwidth 0-10 Hz, amplitude +/-30 N) was superimposed on the preload causing small amplitude trunk movements. Nonparametric impulse response functions of trunk dynamics were computed and revealed that the system exhibited underdamped second-order behavior. Second-order trunk dynamics were determined by calculating the best least-squares fit to the IRF. The quality of the model was quantified by comparing estimated and observed displacement variance accounted for (VAF), and quality of the second-order fits was calculated as a percentage and referred to as fit accuracy. Mean VAF and fit accuracy were 87.8 +/- 4.0% and 96.0 +/- 4.3%, respectively, indicating that the model accurately represented active trunk kinematic response. The accuracy of the kinematic representation was not influenced by preload or gender. Mean effective stiffness was 2.78 +/- 0.96 N/mm and increased significantly with preload (p < 0.001), but did not vary with gender (p = 0.425). Mean effective damping was 314 +/- 72 Ns/m and effective trunk mass was 37.0 +/- 9.3 kg. We conclude that stochastic system identification techniques should be used to calculate effective trunk stiffness and dynamics.

Adult↗
PubMed1996

Computer simulations of voltage clamping retinal ganglion cells through whole-cell electrodes in the soma.

1. Computer simulations of voltage-clamp experiments in retinal ganglion cells were implemented to better understand the insights that can be obtained with this physiological approach. 2. Simulation studies of voltage clamping were based on the contemporary approach of using whole-cell recordings with low resistance electrodes attached to the soma. Realistic ganglion cell morphologies were provided by cell staining experiments in the mudpuppy retina; selected cells included small-, medium-, and large-field neurons whose morphologies were entered into a computer through a neuron tracing program. 3. Values for the specific membrane resistance (Rm) varied from 5,000 to 100,000 omega/cm2 to conform to the range of Rm values obtained with intracellular sharp electrodes and whole-cell recordings. 4. Synaptic input currents were simulated by injecting current with and without an underlying conductance change into different regions of the dendritic tree. The time-variant waveform of the current included a combined transient and sustained component similar to the waveform of ON-bipolar activation. 5. Simulations were base on 1) intact structures, which included the soma and the entire dendritic tree, and 2) a more limited cell geometry that included representation of the soma, but only part of the dendritic tree, to represent the restricted morphology that might be rendered after cutting the retina into 150-microns cross sections for retinal slice experiments. 6. The results of this study indicate that voltage clamping from the soma, with optimal, low resistance electrodes and series resistance compensation, provides an error-free voltage clamp for slow signals that are generated within a small electrotonic distance from the soma (approximately 0.1 lambda). 7. The ideal voltage-clamp conditions are optimized when synaptic conductances are small and nonlinear membrane elements are minimally activated: small-field neurons best approximate these conditions, but clamping errors are evident in these cells when more distal branches are activated. The degree of error in voltage clamping was much greater when medium-and large-field neurons were evaluated. 8. It was not possible to clamp action potentials (nonpropagating) even when they were generated near the soma in any of the three model cells examined. 9. Experimental paradigms were developed to demonstrate that inadequate voltage clamping can lead to errors in the interpretation of experimental data when relevant variables are not taken into consideration. Suggestions are made for determining and optimizing favorable clamp conditions.

Action Potentials↗
PubMed2006

Perceived orientation of complex shape reflects graded part decomposition.

Although the orientation of line segments and simple shapes is a well-studied area of vision, little is known about geometric factors that influence perceived orientation of complex multipart shapes. The study of these factors is of interest because it allows for an insight into the basic problem of how local geometric attributes are integrated perceptually into a global shape representation. We examined the perceived orientation of two-part shapes using an adjustment method and a 2AFC task. In particular, we investigated the influence of the perceptual salience, or distinctiveness, of a part--as defined by the turning angles at its boundaries--and its area relative to the main "base" part. In contrast to previous results on simple shapes, our results exhibited large and systematic deviations of perceived orientation from the principal axis of the shape. For shapes with sharp part boundaries, perceived global orientation deviated maximally from the principal axis and was approximated by the axis of the main base part of the shape. With weakening part boundaries, the perceived orientation gradually approached the principal axis of the entire shape, reflecting that both parts were taken into account in estimating orientation. The results are consistent with a differentially weighted principal-axis computation in which the attached part is given systematically lower weighting with increasing turning angles at the part boundaries. They thus allow a quantitative characterization of part salience in terms of part independence: Turning angles at a part's boundaries determine the extent to which its influence is perceptually separable from the rest of the shape. We suggest that Robust Statistics may provide a useful framework for quantifying the influence of part segmentation on visual estimation.

Adult↗
PubMed2004

Association of Fcgamma receptor IIa genotype with chronic periodontitis in Caucasians.

BACKGROUND: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors IIIa and IIIb (FcgammaRIIIa and FcgammaRIIIb) have been shown as risk factors for periodontitis. The aim of this study is to examine whether FcgammaRIIa polymorphism is associated with a disease risk as well. METHODS: Baseline periodontal and general health examinations were carried out on 1,221 Caucasian adults. From these, 422 subjects with moderate to severe, or little or no periodontal disease were assigned to two groups according to their mean clinical attachment loss (CAL). Subjects with mean CAL > or = 2.94 mm were diagnosed with chronic periodontitis (n = 213, 62 never-smokers and 151 smokers). Subjects with mean CAL < or = 1.77 mm were considered as having little or no periodontal disease and designated as controls (n = 209, 125 never-smokers and 84 smokers). The FcgammaRIIa genotype for three bi-allelic polymorphisms (FcgammaRIIa-R/ R131, R/H131, and H/H131) was determined by means of allele-specific polymerase chain reactions. RESULTS: The distribution of FcgammaRIIa genotype between the patient and control groups was significantly different, with enrichment of the high ligand-binding genotype FcgammaRIIa-H/H131 in the patients (patients versus controls: 36.6% versus 25.4%; P = 0.04). Multivariate logistic regression model demonstrated that subject age and gender, smoking, and the FcgammaRIIa genotype were significantly associated with severity of chronic periodontitis. For smokers, a significant over-representation of FcgammaRIIa-H/H131 in the patient group compared to the control group (patients versus controls: 35.1% versus 19.0%; P = 0.03). Additionally, smokers with FcgammaRIIa-H/H131 exhibited significantly greater mean CAL (mean +/- SE: 3.44 +/- 0.16 mm) than those with FcgammaRIIa-R/H131 (2.91 +/- 0.14 mm) and R/R131 (2.82 +/- 0.16 mm) (P = 0.04). There was no association between FcgammaRIIa genotype and the disease susceptibility or severity in subjects who had never smoked. CONCLUSIONS: Our results suggest that the FcgammaRIIa-H/H131 genotype may be associated with chronic periodontitis risk (and disease severity) in Caucasian smokers. Further studies with families and studies of mechanisms are necessary to help establish the extent to which this is a genetic determinant of periodontal diseases.

Age Factors↗
PubMed1996

Lie as narrative truth in abused adopted adolescents.

Two case examples of abused adopted adolescents are discussed to highlight tension within the treatment relationship when the therapist is expected to accept without question a clearly unbelievable story. These examples illustrate how the lies of such youths can function as narrative truth. The unbelievable tales that emerge in the therapeutic work effectively alter the adolescents' perceptions about the perplexing loss of continuity, both internal and external, that occurred when they were removed from their homes. Characters in the stories represent fragmented self- and object-representations as victim, abuser, rescuer, and passive onlooker. Counterparts to the patient as victim, abuser, rescuer, and passive onlooker can be recognized in the therapist's subjective responses. If the therapist can use countertransference to inform an understanding of the treatment process, an appreciation emerges that the truth of the lie is in its impact. Decisions about how to intervene can then be crafted. The second separation-individuation intrinsic to adolescent development is understood to provide a ripe opportunity for this working-through process.

Adolescent↗
PubMed1992

The Eros of dreaming.

This paper examines the aspects of dreaming derived from the principle of Eros, the life instinct as described by Freud in Beyond the Pleasure Principle. The life instinct is interpreted in information-processing terms, as the inverse of entropy. The paper emphasizes the role of condensation as a mechanism that binds together the representations of present and past events in the imagery of the dream. This distinguishes it from displacement, which appears to be a mechanism whose function is solely defensive. The role of the dream in finding a common ground between current and past experience (Galton's method of comparison by superimposition) is discussed in detail. It is suggested that condensation is a primitive cognitive mechanism at work in many kinds of mental activity. The implications of this idea for psychoanalysis and for the creative process in general are explored in brief.

Dreams↗
PubMed1996

A cardiac muscle model relating sarcomere dynamics to calcium kinetics.

A muscle model establishing the link between cross-bridge dynamics and intracellular Ca2+ kinetics was assessed by simulation of experiments performed in isolated cardiac muscle. The model is composed by the series arrangement of muscle units formed by inextensible thick and thin filaments in parallel with an elastic element. Attached cross-bridges act as independent force generators whose force is linearly related to the elongation of their elastic structure. Ca2+ kinetics is described by a four-state system of sites on the thin filament associated with troponin C: sites with free troponin C (T), sites with Ca2+ bound to troponin C (TCa); sites with Ca2+ bound to troponin C and attached cross-bridges (TCa*); and sites with troponin C not associated with Ca2+ and attached cross-bridges (T*). The intracellular Ca2+ concentration ([Ca2+]) is controlled solely by the sarcoplasmic reticulum through an inflow function and a saturated outflow pump function. All the simulations were performed using the same set of parameters. The model was able to reproduce the following experiments in cardiac muscle: (a) time course of isometric force (peak force: 46.5 mN/mm2), intracellular [Ca2+] (peak [Ca2+]: 1.5 microM); (b) force-length-[Ca2+] relations; (c) transient response of force to step changes in length; (d) force-velocity relation (maximum velocity: 3 microns/s); (e) the force response to length pulses to estimate the time course of [TCa]; (f) force response to quick releases showing the superactivating and deactivating effects of shortening; (g) stiffness response to sinusoidal length changes; and (h) time course of active state. The good accordance of the simulations with experimental results indicates that the model is an adequate representation of the link between cross-bridge dynamic behaviour and Ca2+ kinetics.

Animals↗
PubMed2001

Abnormalities of motor and praxis imagery in children with DCD.

In an earlier study using the visually guided pointing task (VGPT) the authors showed that the timing of imagined movement sequences in children with developmental coordination disorder (DCD) does not conform to the conventional speed-for-accuracy trade-off (or Fitts' law [P.M. Fitts, Journal of Experimental Psychology 47 (1954) 381-391]) that occurs when the distance and accuracy requirements of movements are varied [P. Maruff, P.H. Wilson, M. Trebilcock, J. Currie, Neuropsychologia 37 (1999b) 1317-1324]. The present study sought to replicate this earlier finding and to examine (using a weight manipulation) whether this deficit was also attributable to inaccurate programming of relative force. The chronometry of real and imagined movements was investigated in a group of 20 children with DCD aged between 8 and 12 years and a group of controls matched on age and verbal IQ (VIQ). Movement duration was tested for real and imagined movements using the preferred hand, with the VGPT performed under two load conditions: with and without the addition of a weight attached to a pen. Group means of each subjects' mean movement duration were calculated and plotted against target width for each of the four conditions [Movement type (2) x Load (2)] and a logarithmic curve was fitted to the data points. In the control group, the speed-for-accuracy trade-off for both real and imagined performance conformed to Fitts' law under each load condition. In the DCD group only real movements conformed to Fitts' law. Moreover, the effect of load differed between groups--for real movements, movement duration did not differ between load and no-load conditions for either group, while for imagined movements, movement duration increased under the load condition for the control group only. These results replicate and extend the results of our earlier study. This pattern of performance suggests that children with DCD have an impairment in the ability to generate internal representations of volitional movements which may reflect an impaired ability to process efference copy signals. The ability to programme both relative force and timing appears to underly this difficulty. Results have implications for the use of (guided) motor imagery training in order to facilitate the development of motor skill in children with DCD.

Child↗
PubMed1990

The Depressive Experiences Questionnaire: a critical review.

The Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976) is critically reviewed. First the developmental, object representations theory differentiating depression into anaclitic and introjective subtypes is presented. The DEQ factors of Dependency and Self-Criticism were initially found to be consistent with these clinically meaningful depressive subtypes. Subsequent research has generally demonstrated that these subtypes, at least as measured by the DEQ, do not hold up well in clinical populations. Furthermore, the validity of the developmental theory of these subtypes is weak. We suggest that more internally consistent and distinct factors should be developed from clinical populations because of their potential clinical usefulness.

Depressive Disorder↗
PubMed1996

An empirical study of the psychodynamics of suicide: a preliminary report.

Preliminary results from a study of psychodynamic constructs are presented based on data from inpatients following a suicide attempt. The study examines the association between four psychodynamic constructs, severity of suicidal intent, and severity of depressive symptomatology in a sample of hospitalized suicide attempters. Higher levels of suicidal intent were associated with less differentiated self and object representations and less emotional investment in relationships. More severe depressive symptoms in suicide attempters were correlated with more self-targeted anger, less eternally directed anger, higher levels of shame and guilt, more affectively negative views of relationships, greater use of maladaptive and self-sacrificing defenses, and more impaired reality testing. These findings offer some preliminary empirical support for the validity of psychodynamic theories of suicidal behavior.

Adult↗
PubMed1993

The roles of mental representations and mental processes in therapeutic action.

In this paper we describe two models of the psychoanalytic treatment of mental disturbance. The first describes the mechanism by which the patient is helped to recover threatening ideas and feelings which have been repudiated or distorted as a result of conflict and defense. The second points to the therapeutic effects of engaging previously inhibited mental processes within the psychoanalytic encounter. The two forms of therapeutic action imply two distinct means available to the individual to deal with psychological conflict. They highlight different aspects of the psychoanalytic process and technique in child and adult psychoanalysis.

Adult↗
PubMed2004

To have and to hold: on the experience of having an other.

This paper reconsiders familiar concepts (such as internalization, object representation, and object constancy) in light of the notion of having, in order to facilitate creative thinking about how patients are or are not capable of experiencing analysts-and how analysts allow them to do so. The meaning of Other-having is examined from both a theoretical and a subjective point of view. The author suggests that the sense of having an Other results from positive real experiences, and that the ability to have an Other is the sine qua non, the building block, of all mental functions that require empathy.

Adult↗
PubMed2004

Incorporation of an invasive object.

The author discusses the experience of 'being invaded' that is sometimes communicated by certain severely disturbed patients. The complaint can sometimes be couched in terms of bodily suffering and such patients may state that they have the experience of a 'foreign body' inside. It is suggested that these patients have suffered severe early failure of containment of their projections, while at the same time they have incorporated primitive characteristics of the object that have been powerfully projected into them. An object that invades in this way, it is suggested, experiences a compulsive need to expel unbearable states of mind using others as a repository. The infant incorporates these violent projections as part of his own mental representational system, and normal identification processes are disrupted. There follows impairment of the development of the sense of self. Clinical examples of how the invasive experience manifests itself in the analytic setting and in the transference and countertransference are presented. It is argued that this highly complex form of early subject-object interaction (prior to the differentiation of psyche-soma) is more likely to be found in severely narcissistically disturbed individuals. Some reflections on the origins of invasive phenomena are given.

Adult↗
PubMed2000

Involvement of the hippocampus and associative parietal cortex in the use of proximal and distal landmarks for navigation.

Rats with dorsal hippocampus or associative parietal cortex (APC) lesions and sham-operated controls were trained on variants of the Morris water maze navigation task. In the 'proximal landmark condition', the rats had to localize the hidden platform solely on the basis of three salient object landmarks placed directly in the swimming pool. In the 'distal landmark condition', rats could rely only on distal landmarks (room cues) to locate the platform. In the 'beacon condition', the platform location was signaled by a salient cue directly attached to it. Rats with hippocampal lesions were impaired in the distal and to a less extent in the proximal landmark condition whereas rats with parietal lesions were impaired only in the proximal landmark condition. None of the lesioned groups was impaired in the beacon condition. These results suggest that the processing of information related to proximal, distal landmarks or associated beacon are mediated by different neural systems. The hippocampus would contribute to both proximal and distal landmark processing whereas the APC would be involved in the processing of proximal landmarks only. Navigation relying on a cued-platform would not require participation of the hippocampus nor the APC. Assuming that the processing of proximal landmarks heavily depends on the integration of visuospatial and idiothetic information, these results are consistent with the hypothesis that the APC plays a role in the combination of multiple sensory information and contributes to the formation of an allocentric spatial representation.

Animals↗
PubMed2005

Clinical implications of the development of the person.

The Minnesota longitudinal study of parents and children from birth to adulthood provides both a theoretical framework and a host of empirical findings that can serve to bridge the gap between research and clinical application. Key among these findings are: (a) the ongoing impact of early relationship experiences throughout the years, even with later experience and circumstances controlled; (b) the cumulative nature of experience and its continual impact with current context; (c) the important role of adult partner relationships; (d) the increasingly active role of the persons themselves in their own development; and (e) the interplay between experience, representation, and ongoing adaptation. These findings, and the theoretical structure underlying them, suggest the need for complex, comprehensive intervention that begins early, with a focus on altering the quality of parent - child relationships. At the same time, additional components, including couples therapy and efforts to alter the child's inner constructions of experience, are clearly suggested. One must attend to forces maintaining children on maladaptive developmental pathways once established, as well as understanding the factors that initiated such pathways.

Adaptation, Psychological↗
PubMed1989

Indices of psychopathology in the Rorschachs of boys with severe gender identity disorder: a comparison with normal control subjects.

Recent clinical and empirical studies of boys with Gender Identity Disorder (GID) of Childhood suggest that severe behavioral disturbance exists beyond their feminine preoccupations. This study examines the thought organization and object representational paradigms of a sample of GID boys (n = 26) in a blind comparison with a normal subgroup (n = 18). Rorschach test protocols were used to compare the groups along these two more internal measures of personality organization. As hypothesized, the GIC group was found to have more pathological scores than the normal group on the Mutuality of Autonomy (MOA) Scale and a thought disorder hierarchy. The findings suggest that GID boys do not suffer solely from gender symptomatology but are disturbed in other aspects of their ego functioning as well.

Child↗