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PubMed2006

Awareness is relative: dissociation as the organisation of meaning.

This essay discusses how the organisation of mental material within the cognitive system can influence consciousness and awareness, and presents a theory of dissociation based on the premise that awareness is relative, contingent on the activated representation of the ongoing event being linked to the activated self-representation. It allows four possible variations of integration: (i) non-integrated experience--perceptions about an object/event are either not perceived or they remain at the sensory level: traditional dissociative states, amnesia, depersonalisation etc; (ii) variably integrated experience--activation of information of a specific valence about an object blocks activation of information of contrasting valence: splitting; (iii) alternatively integrated experience--experience is integrated into a specific, limited active self-representation: fugue and multiple identity states; (iv) dis-integrated experience-the ongoing experience of innate drives and needs is no longer consistently activated in the core self-representation: repression and isolation.

Awareness↗
PubMed1992

Imaginal, sensory, and cognitive experience in spontaneous recovery from alcoholism.

Although alcoholism is often regarded as an intractable disorder that requires intensive treatment, studies of the natural history of alcoholism indicate that unaided, spontaneous recovery may be the most common pathway to remission from alcoholism. Negative environmental consequences of alcoholic drinking have been invoked to explain spontaneous recovery, but a more compelling reason for sudden changes in drinking behavior concerns shifts in the personal meanings surrounding alcohol use. Extensive interviews in a multimodal format were conducted with two groups of alcoholics: one group comprised of 7 subjects who spontaneously recovered without treatment and the other group comprised of 9 people who believed formal treatment was necessary to abstain from drinking. Spontaneously recovered alcoholics reported experiencing vivid sensations and images at the time they decided to quit drinking, and they reported subsequent transformations of their personal identities. Active alcoholics reported no comparable experiences in imaginal, sensory, and cognitive modalities. Implications of the results for current alcoholism treatments are discussed.

Adult↗
PubMed1980

Acculturation and mental disorder in the Inuit.

The phenomenon of acculturation stress is described with particular reference to the subsequent development of the transitional role conflict. The adolescent and young adult male Eskimo is especially susceptible to the anxiety generated by the process of acculturation and it is the interaction of this external stress with the bio-psychosocial characteristics of the individual within his ecological group, that may lead to an increased incidence of mental disorder. The clinical picture that develops will depend on the complex interaction of this psychosocial stressor and the level of ego development and its accompanying defence and coping strategies. We see how the development of manifest psychopathology in two young Inuit males was intimately associated with the stresses of acculturation acting upon personalities characterized by a low self-esteem and negative self-image, feelings of emasculation and a state of anomie. Coping and defensive strategies exhibited both similarities (drugs, alcohol, withdrawal, actin out) and differences (psychosis versus dissociation). The value of modified supportive therapy with continuity of care aimed at increasing self-esteem through sublimation, identification, reduction of dependency and encouragement of growth and autonomy is described, as are measures aimed at primary prevention.

Acculturation↗
PubMed1999

A specific transition state for S-peptide combining with folded S-protein and then refolding.

We measured the folding and unfolding kinetics of mutants for a simple protein folding reaction to characterize the structure of the transition state. Fluorescently labeled S-peptide analogues combine with S-protein to form ribonuclease S analogues: initially, S-peptide is disordered whereas S-protein is folded. The fluorescent probe provides a convenient spectroscopic probe for the reaction. The association rate constant, kon, and the dissociation rate constant, koff, were both determined for two sets of mutants. The dissociation rate constant is measured by adding an excess of unlabeled S-peptide analogue to a labeled complex (RNaseS*). This strategy allows kon and koff to be measured under identical conditions so that microscopic reversibility applies and the transition state is the same for unfolding and refolding. The first set of mutants tests the role of the alpha-helix in the transition state. Solvent-exposed residues Ala-6 and Gln-11 in the alpha-helix of native RNaseS were replaced by the helix destabilizing residues glycine or proline. A plot of log kon vs. log Kd for this series of mutants is linear over a very wide range, with a slope of -0.3, indicating that almost all of the molecules fold via a transition state involving the helix. A second set of mutants tests the role of side chains in the transition state. Three side chains were investigated: Phe-8, His-12, and Met-13, which are known to be important for binding S-peptide to S-protein and which also contribute strongly to the stability of RNaseS*. Only the side chain of Phe-8 contributes significantly, however, to the stability of the transition state. The results provide a remarkably clear description of a folding transition state.

Amino Acid Sequence↗
PubMed2006

Between Wallenberg syndrome and hemimedullary lesion: Cestan-Chenais and Babinski-Nageotte syndromes in medullary infarctions.

In comparison with the lateral (Wallenberg), medial (Dejerine) and hemimedullary (Reinhold) medulla oblongata syndromes, the Babinski-Nageotte and Cestan-Chenais syndromes are much less familiar cerebrovascular disorders. While the Babinski-Nageotte syndrome is usually confused with the hemimedullary syndrome, reports of the extremely rare Cestan-Chenais syndrome are missing from the modern neurological literature. The pathological and magnetic resonance imaging (MRI) correlations of the Cestan-Chenais syndrome have not been shown so far. We compared clinical and MRI features of two patients exhibiting classical Babinski-Nageotte and Cestan-Chenais syndromes according to their original descriptions with those of three patients with lateral, medial and hemimedullary syndromes. Our study shows that Babinski-Nageotte syndrome includes all symptoms of the Wallenberg syndrome and additionally contralateral hemiparesis due to a spreading of the "Wallenbergian" lateral lesion to the pyramidal tract. The Cestan-Chenais syndrome includes all symptoms of the Babinski-Nageotte syndrome with the exception of the ipsilateral cerebellary hemiataxia because of sparing of the posterior spinocerebellar tract. The Babinski-Nageotte syndrome is neither clinically nor on MRI identical with hemimedullary syndrome. Hypoglossal palsy, an invariable symptom of hemimedullary lesion is not part of the Babinski-Nageotte syndrome. The contralateral hypesthesia is dissociated in the Babinski-Nageotte syndrome. The Babinski-Nageotte and Cestan-Chenais syndromes are intermediolateral medullary syndromes with all (Babinski-Nageotte) or nearly all (Cestan-Chenais) features of the lateral and some features of the medial medulla oblongata syndromes.

Adult↗
PubMed1992

Functional neuroanatomy of face and object processing. A positron emission tomography study.

Studies of brain-damaged patients have revealed the existence of a selective impairment of face processing, prosopagnosia, resulting from lesions at different loci in the occipital and temporal lobes. The results of such studies have led to the identification of several cortical areas underlying the processing of faces, but it remains unclear what functional aspects of face processing are served by these areas and whether they are uniquely devoted to the processing of faces. The present study addresses these questions in a positron emission tomography (PET) study of regional cerebral blood flow in normal adults, using the 15 oxygen water bolus technique. The subjects participated in six tasks (with gratings, faces and objects), and the resulting level of cerebral activation was mapped on images of the subjects' cerebral structures obtained through magnetic resonance and was compared between tasks using the subtraction method. Compared with a fixation condition, regional cerebral blood flow (rCBF) changes were found in the striate and extrastriate cortex when subjects had to decide on the orientation of sine-wave gratings. A face-gender categorization resulted in activation changes in the right extrastriate cortex, and a face-identity condition produced additional activation of the fusiform gyrus and anterior temporal cortex of both hemispheres, and of the right parahippocampal gyrus and adjacent areas. Cerebral activation during an object-recognition task occurred essentially in the left occipito-temporal cortex and did not involve the right hemisphere regions specifically activated during the face-identity task. The results provide the first empirical evidence from normal subjects regarding the crucial role of the ventro-medial region of the right hemisphere in face recognition, and they offer new information about the dissociation between face and object processing.

Adult↗
PubMed1989

Analysis of granulomatous arteritis in MRL/Mp autoimmune disease mice bearing lymphoproliferative genes. The use of mouse genetics to dissociate the development of arteritis and glomerulonephritis.

MRL/Mp mice bearing the lymphoproliferation gene (lpr) spontaneously develop systemic granulomatous arteritis coincident with glomerulonephritis (GNP). Although the association of lpr-dependent lymphoproliferation in these mice seems to be a prerequisite for the development of granulomatous arteritis, the genetic basis is poorly understood. The first approach to this problem was to study the ability of another, nonallelic, lymphoproliferative gene, gld (generalized lymphoproliferative disease), inducing arteritis in MRL/Mp mice. The gld gene was placed on an MRL/Mp background by producing reciprocal (MRL/Mp-+/+ X C3H/Hej-gld/gld)F2 hybrid mice. Seventeen percent of these mice with lymphoproliferation had arteritis and GNP, suggesting that more than one lymphoproliferative gene could induce GNP and arteritis in an MRL/Mp background. Next, the effect of rearrangements in the genetic background of MRL/Mp-lpr/lpr mice by hybridization with non-autoimmune lpr-bearing mice was examined. This was done by making MRL/Mp-lpr/lpr X reciprocal (MRL/Mp-lpr/lpr X C57BL/6-lpr/lpr)F1 mice. Thirty-three percent of these mice developed arteritis, but one third of these did not get GNP, thus showing that susceptibility to arteritis was separate from GNP. The histopathologic features of the arteritis in both the F2 hybrids and the backcross mice were granulomatous and were identical to those seen in MRL/Mp-lpr/lpr mice. These findings suggested that it might be possible to dissociated two components (arteritis and GNP) of a severe autoimmune disease of MRL/Mp mice and to study their pathogenesis separately.

Animals↗
PubMed1991

An alternative explanation for the genesis of closed-lock symptoms in the internal derangement process.

Clinical and surgical data on 194 operated joints (135 patients) were used to substantiate a new concept challenging the presumed natural history of temporomandibular internal derangement (ID). A number of findings were incompatible with the traditional depiction of a progressive process based on gradual changes in disc position and shape. These findings were a lack or correlation between increasing age and the stages of the process; the percentage of patients in the third stage (closed lock) with limited opening (less than 25 mm) too severe to be caused solely by a nonreducible, displaced disc; the unexpectedly high incidence (greater than 50%) of normally shaped discs in the third stage of the process. A specific condition of severe and stubborn limited maximal mouth opening caused by total cessation of gliding, liable to occur at any age and unrelated to disc shape or position, which responds successfully to simple treatment by lavage and lysis, pressured injection, or arthrocentesis, was discerned. Lack of gliding was attributed to adherence of the disc to the fossa by a reversible effect such as a vacuum and/or decreased volume of synovial fluid of high viscosity. This condition was deemed worthy of an independent identity, dissociated from disc displacement, as a causative factor in the second and third stages of ID, and particularly as an aid to accurate diagnosis and treatment.

Adolescent↗
PubMed1998

Expression of proteins controlling transbilayer movement of plasma membrane phospholipids in the B lymphocytes from a patient with Scott syndrome.

Scott syndrome is a rare inherited bleeding disorder in which platelets and other blood cells fail to promote normal assembly of the membrane-stabilized proteases of the plasma coagulation system. The defect in Scott blood cells is known to reflect inability to mobilize phosphatidylserine from inner plasma membrane leaflet to the cell surface in response to an elevation of Ca2+ at the endofacial surface. To gain insight into the molecular basis of this membrane defect, we examined the expression in Scott cells of plasma membrane proteins that have been implicated to participate in the accelerated transbilayer movement of plasma membrane PL. By both reverse transcriptase-polymerase chain reaction (RT-PCR) and functional assay, the level of expression of the multidrug resistance (MDR)1 and MDR3 P-glycoproteins in immortalized B-lymphoblast cell lines from the patient with Scott syndrome were indistinguishable from matched cell lines derived from normal controls. Whereas the plasma membrane of Scott cells are insensitive to activation of the plasma membrane PL scramblase pathway, it had been shown that PL scramblase protein isolated from detergent-solubilized Scott erythrocytes exhibits normal function when incorporated into proteoliposomes (Stout JG, Basse F, Luhm RA, Weiss HJ, Wiedmer T, Sims PJ: J Clin Invest 99:2232, 1997). Consistent with this finding in Scott erythrocytes, we found that Scott lymphoblasts expressed normal levels of PL scramblase mRNA and protein, and that the deduced sequence of PL scramblase in Scott cells is identical to that of normal controls. These data suggest that the defect in Scott syndrome is related either to aberrant posttranslational processing of the PL scramblase polypeptide or to a defect or deficiency in an unknown cofactor that is required for normal expression of plasma membrane PL scramblase function in situ, or alternatively, reflects the presence of a detergent-dissociable inhibitor of this pathway.

B-Lymphocytes↗
PubMed1997

Dissociation between the perception of body verticality and the visual vertical in acute peripheral vestibular disorder in humans.

Estimates of the subjective visual and postural vertical were obtained from five patients with acute peripheral vestibular lesions and 20 normal subjects. The visual vertical was assessed by asking the subjects to align a target line to earth vertical by means of remote control. Postural vertical judgments were obtained by exposing them to rotational displacements in the roll plane while sitting on a motor-driven chair and requiring them to align their body to vertical using a joystick control. While the patients showed strong deviations of the visual vertical towards the lesion side, their postural vertical judgments remained veridical. We conclude that the above perceptions are not processed identically and that the participating sensory systems are differently weighted during these tasks.

Adult↗
PubMed2000

What is extinguished in auditory extinction?

Extinction is a frequent sequel of brain damage, whereupon patients disregard (extinguish) a contralesional stimulus, and report only the more ipsilesional stimulus, of a pair of stimuli presented simultaneously. We investigated the possibility of a dissociation between the detection and the identification of extinguished phonemes. Fourteen right hemisphere damaged patients with severe auditory extinction were examined using a paradigm that separated the localization of stimuli and the identification of their phonetic content. Patients reported the identity of left-sided phonemes, while extinguishing them at the same time, in the traditional sense of the term. This dissociation suggests that auditory extinction is more about acknowledging the existence of a stimulus in the contralesional hemispace than about the actual processing of the stimulus.

Acoustic Stimulation↗
PubMed2001

New Glucocorticosteroids with an improved therapeutic ratio?

Glucocorticoids (GCs) remain the most effective therapy for inflammatory disorders. In terms of asthma, topical steroids are the mainstay for controlling the inflammatory component of the disease. However, their use is limited by the constellation of adverse effects associated with chronic, oral steroid use and the long-term adverse effects associated with inhaled steroid use. These include suppression of hypothalamic--pituitary axis, osteoporosis, reduced bone growth in the young, opportunistic infections, behavioural alterations, and disorders of lipid metabolism. Most of these effects may be attributable to the endocrine activity of steroids and are largely identical to the syndromes of endogenous corticosteroid excess (Cushing's Syndrome). Thus, the Holy Grail of steroid pharmacology is the development of agents which have a markedly improved therapeutic ratio than current steroids, especially on systemic administration. This may be achieved by the identification of molecules which elicit marked antiinflammatory effects, but have a minor impact on endocrine responses. Dissociated corticosteroids are ligands for the glucocorticoid receptor that may offer the potential for a more selective antiinflammatory profile.

Asthma↗
PubMed1994

Left visuo-spatial neglect can be worse in far than in near space.

We tested five patients with marked left-sided visuo-spatial neglect and two control subjects on a test of line bisection. A series of horizontal lines was presented to each subject, who had to indicate the centre with a projection light-pen. All five patients misplaced the centre to the right, in accordance with their left-sided neglect. However, in all five the angular displacement was greater for lines well beyond reach, than for lines of identical angular size within reaching distance. This result, precisely because it is opposite to that of a previous report, supports the conclusion that there are separate dissociated neural systems concerned with the perception of, and response to, stimuli in near and far space.

Aged↗
PubMed1999

Validation of a French version of the Dissociative Experiences Scale in a rape-victim population.

OBJECTIVE: To appreciate the extent and the features of dissociation in a hypothesized highly dissociated population, rape trauma victims, while assessing construct validity and internal consistency of a French version of the Dissociative Experiences Scale (DES), a simple screening instrument for dissociative symptoms. METHODS: One hundred and forty rape victims (mean age 23.6 years, 9% male) consecutively attending a Consultation for Victims of Psychological Trauma at the university hospital in Tours, France, were assessed through a French version of the 28-item self-rated DES. RESULTS: The mean score (24.1) was high, and 33% of the scores exceeded a threshold set at 30. The Principal Components Analysis of the DES ratings yielded a 3-factor solution: depersonalization-derealization, amnestic fragmentation of identity, and absorption-imaginative involvement. DES reliability was studied through computation of Cronbach's alpha coefficient (0.94). CONCLUSION: During validation of a French version of the DES, the study showed that dissociation is considerably linked to rape-trauma victim populations.

Adolescent↗
PubMed1999

Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides.

The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and learning. In this study, we identified a synthetic peptide-ligand of the NCAM Ig1 module by combinatorial chemistry and showed it could modulate NCAM-mediated cell adhesion and signal transduction with high potency. In cultures of dissociated neurons, this peptide, termed C3, stimulated neurite outgrowth by activating a signaling pathway identical to that activated by homophilic NCAM binding. A similar effect was shown for the NCAM Ig2 module, the endogenous ligand of NCAM Ig1. By nuclear magnetic resonance spectroscopy, the C3 binding site in the NCAM Ig1 module was mapped and shown to be different from the binding site of the NCAM Ig2 module. The C3 peptide may prove useful as a lead in development of therapies for neurodegenerative disorders, and the C3 binding site of NCAM Ig1 may represent a target for discovery of nonpeptide drugs.

Amino Acid Sequence↗
PubMed2003

To be and not to be: the paradox of the emerging professional stance.

PURPOSE: Understanding how students resolve professional conflict is essential to teaching and evaluating professionalism. The purpose of this study was to refine an existing coding structure of rationalizations of student behaviour, and to further our understanding of students' reasoning strategies in the face of perceived professional lapses. METHODS: Anonymous essays were collected from final year medical students at two universities. Each essay included a description of a specific professional lapse, and a consideration of how the lapse was dealt with. Essays were analysed using grounded theory. The resulting coding structure was applied using NVivo software. RESULTS: Twenty essays, containing 147 instances of articulated reasoning, were included. Three major categories (and several subcategories) of reasoning strategies emerged: Narrative Attitude (deflection or reflection), Dissociation (condescension or identity mobility), and Engagement (with associated action or no action). This data set revealed a wider range of Narrative Attitude than in the original study, confirmed the dominance of Dissociation as a reasoning strategy, and, perhaps paradoxically, also revealed significant evidence of action on the part of the students (predominantly directed towards dealing with the consequences of a lapse or confronting the lapser). Most of these actions were perceived to be ineffective. CONCLUSIONS: Encountering a professional lapse can be a paradoxical and profoundly disordering experience for students. When students report these experiences, they invoke reasoning strategies that enable them to re-story the lapse. Their methods of re-storying provide insight into the double-binds that students experience, their efforts to transcend these double-binds, and, through these, their emerging professional stance.

Attitude of Health Personnel↗
PubMed1974

Mechanism of renaturation of pyruvate kinase of Saccharomyces carlsbergensis: activation by L-valine and magnesium and manganese ions.

Pyruvate kinase (EC 2.7.1.40) of S. carlsbergensis is a tetrameric enzyme, composed of four identical subunits each of which contains 1 mole of L-valine noncovalently bound. The enzyme readily dissociates into monomeric units. L-Valine and magnesium or manganese ions are specific primers of the renaturation process of the enzyme. The amino acid induces renaturation with a K(0.5) of 17 muM and a pseudo first-order rate constant of 0.019 min(-1) at 25 degrees with respect to the monomeric species, indicating that L-valine influences the folding of the monomeric form from a disordered state to its native conformation being followed by a spontaneous reassociation with formation of the tetrameric enzyme. Independently, magnesium and manganese ions induce the renaturation with a first-order rate constant of the same magnitude.

Enzyme Activation↗
PubMed1993

[Trance states--a case report].

For the first time, trance states have been included in the International Classification (ICD-10) as a separate identity. The case of a 13-year-old boy is presented and the diagnostic process discussed especially the differentiation between trance states and epilepsy. Psychotherapy and the in-patient treatment course are described including the factors facilitating a positive outcome.

Adolescent↗