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Results for “Reactive Attachment Disorder”

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PubMed1982

Orientation of spin labels attached to cross-bridges in contracting muscle fibres.

Electron micrographs showing different cross-bridge orientations in different states of muscle fibres, and X-ray diffraction patterns indicating axial cross-bridge disorder in contracting muscle first suggested that force generation in the contracting muscle involved a change in orientation of the myosin heads that form cross-bridges between thick and thin filaments. This has been supported by subsequent work; the myosin molecule has the required flexibility for changes in orientation. The orientation of muscle tryptophans and of probes attached to the myosin heads of permeable muscle fibres depends on the state of the muscle. Recently, fluorescence polarization fluctuations and time-resolved X-ray diffraction patterns have suggested that cross-bridges of a contracting muscle can rotate. We have used electron paramagnetic resonance (EPR) spectroscopy to monitor the orientation of spin labels attached specifically to a reactive sulphydryl on the myosin heads in glycerinated rabbit psoas skeletal muscle. Previously, it has been shown that the paramagnetic probes are highly ordered in rigor muscle, with a nearly random angular distribution in relaxed muscle. We show here that during the generation of isometric tension, approximately 80% of the probes display a random angular distribution as in relaxed muscle while the remaining 20% are highly oriented at the same angle as found in rigor muscle. These findings indicate that a domain of the myosin head does not change orientation during the power stroke of the contractile interaction.

Actins↗

PubMed2005

Activation of multiple pathways during photoreceptor apoptosis in the rd mouse.

PURPOSE: The primary purpose of this study was to characterize photoreceptor apoptosis in the rd mouse. Given that apoptosis is the final common pathway in many cases of retinal degeneration, the ability to retard or even arrest this process may ameliorate retinal disorders such as retinitis pigmentosa (RP). The absence of any recognized therapy emphasizes the fact that a detailed knowledge of the molecular events involved is necessary to identify rational targets for therapeutic intervention. METHODS: Flow cytometry was used to measure physical and chemical characteristics in the photoreceptor population. Individual cells flow in suspension past one or more lasers, scattering light and emitting fluorescence. Western blot techniques demonstrated cleavage of calpain-specific substrates. Retinal explant cultures were used for inhibitor studies. Postnatal day 10 (P(10)) rd retinas were cultured without retinal pigment epithelium (RPE) attached up to P(17). RESULTS: This study demonstrated calcium overload in the cytosol and subsequently in mitochondria. Mitochondrial membrane depolarization and reactive oxygen species (ROS) were detected later, during the peak of cell death. Analysis of downstream events indicated early activation of calcium-activated calpains. Treatment of rd retinal explants with the calpain inhibitor N-acetyl-Leu-Leu-Nle-CHO (ALLN) successfully inhibited calpain-induced alpha-fodrin cleavage, yet it did not protect against photoreceptor degeneration. Finally, the results demonstrate an increase in the levels of both precursor and processed forms of the aspartate protease cathepsin D. CONCLUSIONS: Excessive calcium influx is an early event that initiates the activation of calcium-activated proteases. However, these proteases are not singularly the cause of death, because their inhibition does not prevent apoptosis. Indeed, the results presented herein suggest that multiple pathways are involved and that each of these components may have to be addressed for cell death to be successfully inhibited.

Animals↗

PubMed2004

Social cognition as a mediator of the influence of family and community violence on adolescent development: implications for intervention.

Several studies have shown that exposure to family and community violence during childhood and adolescence is associated with an increased risk for development of externalizing behavior problems, but less is known about specific mechanisms that mediate this relation. Variations in social cognition serve as one possible mechanism by which these environmental experiences influence aggressive behavior during adolescence. Children who have been maltreated tend to display negatively biased social-cognitive processing styles, which may in turn increase their likelihood of reacting aggressively in ambiguous social situations. Similarly, witnessing community violence is associated with aspects of social cognition, including beliefs that support aggressive responses to threat. Recent studies also suggest that exposure to extreme forms of stress and violence can produce changes in children's neurobiology that may increase their hypersensitivity and reactivity to interpersonal threat. Some of the strongest evidence of the role of social cognition as a mechanism in this association comes from intervention studies which reduced aggressive behavior by targeting negatively biased social-cognitive processing styles.

Adolescent↗

PubMed1994

Methods for evaluation of the adhesive and phagocytic capacities of porcine granulocytes.

The adhesive and phagocytic properties of porcine neutrophils were studied. Blood samples were collected from healthy crossbreed pigs, and granulocytes were obtained by density centrifugation. Adhesion to nylon wool was studied and expression of adhesion molecules was determined by flow cytometry. Three monoclonal antibodies showed reactivity with porcine cells and were thus subsequently used. Freezing and storage at -70 degrees C did not cause major alterations in the expression of adhesion molecules. The kinetics of phagocytosis of serum- and IgG-opsonized yeast cells were studied with fluorescence microscopy and flow cytometry. The influence of various concentrations of normal pooled and heat-inactivated pooled porcine serum on the phagocytic process was elucidated. The phagocytic process was completed more rapidly using C3b- than IgG-opsonized yeast cells. The neutrophils both attached to and ingested the serum-opsonized yeast cells to a large extent. When IgG or heat-inactivated serum were used, only minor attachment was observed. These methods for studies of neutrophil functions can be used both for the diagnosis of immunological disorders and for physiological studies of the neutrophil functions in the pig.

Animals↗

PubMed2002

Redox-linked cell surface-oriented signaling for T-cell death.

T-cell death, which occurs either for ontogenic T-cell selection or for activated T-cell elimination, is normally induced through binding of a specific ligand to cell-surface T-cell receptor for crosslinkage. Heavy metals and carbonyl compounds that bind to protein-reactive groups such as cysteine sulfhydryl groups and lysine epsilon-amino groups may also induce crosslinkage of cell-surface proteins, in part replacing or modifying the ligand-mediated action. This chemical event has been found to accompany clustering of membrane rafts, to which signal-transducing elements such as glycosylphosphatidylinositol-anchored proteins and Src family protein tyrosine kinases (PTKs) are attached, and to trigger the signal transduction for apoptotic T-cell death, inducing mitochondrial membrane potential reduction, caspase activation and DNA fragmentation. As signals potentially upstream of this signaling, activations of PTKs and mitogen-activated protein (MAP) family kinases and production of reactive oxygen species (ROS) were induced following the cell-surface event, and crucial roles of activation of c-Jun amino-terminal kinase and apoptosis signal-regulating kinase 1 by a redox-linked mechanism in the cell-death signaling were demonstrated. Intriguingly, ROS production as well as PTK/MAP family kinase activation occurred in a membrane raft integrity-dependent manner. The redox-linked and cell surface-oriented signal delivery pathway demonstrated here may play an important role in induction of immune disorders by protein reactive group-binding chemicals.

Animals↗

PubMed1988

A developmental-psychodynamic model for diabetic control.

This paper elaborates a psychodynamic-developmental model as a framework for understanding the wide range of adaptive and maladaptive responses to the self-care requirements of diabetes. Early life experience participates with other factors in influencing the ease with which diabetics implement diabetic control. This model emphasizes the importance of the mother-child interaction during the second phase of development, the toddler phase, at which time the child begins to establish a sense of autonomy and control over his own body and its functions, with bowel training viewed as a paradigm for body control. It is postulated that certain types of mothers such as controlling-intrusive mothers, overprotective mothers, or guilty, indifferent, or rejecting mothers create problems for the child related to the development of autonomy and the sense of comfortable and pleasurable control over his bodily functions. Conflicts generated during this period are reactivated with the onset of diabetes and lead to difficulty in implementing control. In some situations where conflicts with the caretaker figure were predominantly limited to aspects of control, trusting relations acted as a substrate for change and improvement in control in a supportive medical environment. Specific management recommendations based upon this model are presented.

Adaptation, Psychological↗

PubMed1998

Reactivity patterns of antiphospholipid antibodies and endothelial cells: effect of antiendothelial antibodies on cell migration.

Antiphospholipid syndrome (APS) is characterized by the presence of a heterogeneous class of antibodies directed against phospholipids and associated with high occurrence of thrombotic complications. Antiendothelial cell antibodies (AECAs) have been identified in various autoimmune disorders including APS, but their reactivity patterns remain unclear. We used eluted endothelial membrane-bound antibodies (EC eluates) to investigate possible cross-reactivity of AECAs and their pathogenic effects on endothelial cell integrity. The heterogeneous and nonspecific nature of AECAs was confirmed by our finding that they cross-react with fibroblasts and platelets and bind to cardiolipin. In addition, platelet-bound antibodies from sera of patients with APS reacted with endothelial cells. A dose-dependent binding of human monoclonal anticardiolipin antibody was demonstrated, but this antibody did not compete with AECAs in EC eluates, indicating that only small portion of AECAs are directed against cardiolipin. Although sera from APS patients prolonged coagulation tests, EC eluates did not affect coagulation, suggesting that AECAs may belong to antiphospholipid antibodies subsets that does not interfere with coagulation. Vascular damage is a common feature of autoimmune disorders associated with AECAs. Possible effects of AECAs on vascular perturbance were investigated by cytotoxicity, attachment, and migration assays. Although AECAs were not shown to be cytotoxic or to affect cell attachment, sera from APS patients caused reduced cellular migration (by 30%), and EC eluates caused even more significant inhibition (by 50%). These findings suggest possible interference of AECAs in vascular repair mechanisms and provide an explanation for the thrombotic complications frequently seen in APS patients.

Antibodies, Antiphospholipid↗

PubMed1999

Contrasting effects of catecholic and O-methylated tetrahydroisoquinolines on hydroxyl radical production.

Tetrahydroisoquinolines (TIQs) are intraneuronal, catecholamine-derived alkaloids that have been implicated in the etiology of Parkinson's disease and in alcohol related disorders. The in vitro production of the cytotoxic hydroxyl radical (*OH) was recorded during the autoxidation of salsolinol (SAL) and salsolinol-1-carboxylic acid (SAL-1C), but not when these two catecholic TIQs were oxidized by tyrosinase. Significantly higher levels of the radical were produced when these catecholic TIQs were incubated with *OH generating complexes, or with chelated iron. In contrast, mono-O-methylated TIQs such as salsoline (SLN) and salsoline-1-carboxylic acid (SLN-1C) did not generate *OH during autoxidation or when incubated with chelated iron or tyrosinase. Radical production by *OH-generating complexes was reduced in the presence of O-methylated TIQs. The neurotoxicity of TIQs may result from their propensity to autoxidize and generate reactive quinoids and ensuing oxygen radicals. The functional significance of the replacement of a hydroxyl group attached to C-7 of SAL or SAL-1C with a methoxyl group remains to be determined. This single structural modification may prevent mono-O-methylated TIQs from participating in catalytic redox cycling reactions that would otherwise augment *OH production. If true, then O-methylation and other cellular mechanisms that circumvent the autoxidation of catecholamine-derived TIQs may reduce the likelihood of these substances forming cytotoxic quinoids and influencing endogenous *OH-generating reactions.

Catechols↗

PubMed1996

T cell immune responses to haptens. Structural models for allergic and autoimmune reactions.

Protein-reactive chemicals, metal salts and drugs, commonly classified as immunological haptens, are major environmental noxes targeted at the immune system of vertebrates. They may not only interfere with this defense system by toxicity alone, but more often by evoking hapten-specific immune responses resulting in allergic and eventually autoimmune responses. Here, we review recent developments in the analysis of the structural basis of hapten recognition, particularly by T lymphocytes, which represent central elements in cell-mediated, as well as in IgE dependent, allergies. A break-through in this field was the finding that T cells detect haptens as structural entities, attached covalently or by complexation to self-peptides anchored in binding grooves of major histocompatibility antigens (MHC-proteins). Synthetic hapten-peptide conjugates were shown to induce hapten-specific contact sensitivity in mice, opening new routes for studying hapten-induced immune disorders.

Amino Acid Sequence↗

PubMedDate not supplied

[Grief and depression in the aged].

Bereavement after recent or earlier losses of loved ones is analyzed in 155 patients older than 60 years. Patients were treated by psychiatrists for endogenous, neurotic, or reactive depression. Bereavement was characterized by depressive syndromes, depressive and anxiety developments, chronification of somatic complaints, induction of endogenous depression, lack of grief or late onset of grief reaction, substance abuse and suicide. Women are more prone to bereavement. Special stressors and characteristic features of bereavement in old age are discussed. The pivotal meaning of interpersonal dependence on lost ones is discussed. Difficulties in the management of bereavement in old people are mentioned.

Adaptation, Psychological↗

PubMed1987

Evidence that tubulin forms an integral membrane skeleton in molluscan gill cilia.

Controlled extraction of intact gill tissue, isolated cilia or reconstituted membrane vesicles with Nonidet P-40 at greater than 4 times the critical micelle concentration, or with octyl glucoside at the critical micelle concentration, delipidates the membrane, leaving a membrane remnant or skeleton of membrane tubulin and associated proteins. This skeleton consists of a disordered reticular protein network in reconstituted membrane vesicles and a similar but more compact sleeve in cilia of extracted tissue. The membrane skeleton is closely apposed to the axoneme and is attached to the outer doublets by fine radial bridges having a 20-24 nm longitudinal periodicity, supporting earlier observations made utilizing a lipophilic cross-linking agent. Higher concentrations of detergent solubilize the membrane tubulin-protein complex, producing 5-10 nm particulate material of low sedimentation coefficient. Dilution of an octyl glucoside solution to below the critical micelle concentration results in disappearance of the particles and reformation of the membrane, indicating that the particles are protein-detergent micelles and not denatured protein. Freeze-fracture electron microscopy reveals no comparable-sized natural particles in the ciliary membrane proper. The reticular material of the membrane skeleton contains tubulin, demonstrated on Lowicryl K4M thin sections by a rabbit polyclonal antibody to sea-urchin egg cytoplasmic tubulin, using gold-labelled secondary antibody. Minimal cross-reactivity is detected prior to Triton-delipidation, suggesting that most membrane tubulin antigenic sites are buried within the bilayer and that the tubulin is not simply adsorbed to the lipid bilayer.

Animals↗

PubMed1995

Development of a heterogeneous amperometric immunosensor for the determination of apolipoprotein E in serum.

Apolipoprotein (apo) E is a constituent of serum lipoproteins and can serve as a diagnostic parameter for the assessment of disorders of lipid metabolism. For the determination of apo E in serum a sandwich-type amperometric immunosensor using disposable membranes was developed. The best results were obtained by using a site-directed attachment of a monoclonal capture antibody to a hydrazide-functionalized membrane surface. Bound antigen was then determined with the aid of a polyclonal antibody labelled with alkaline phosphatase in conjunction with p-aminophenyl phosphate as substrate. In this approach a carbon working electrode (vs. Hg/HgCl2) was used, and enzymatically generated p-aminophenol could be monitored with a detection limit of 40 pmol and a linear range of 26-20000 nM. The sensor displayed a linear response from 50 to 1000 ng ml-1 apo E. In contrast, antibody coupling through primary amino groups led to a total loss of antigen binding capacity in this assay configuration. The approach with site-directed immobilization however, not only allowed the determination of apo E in serum, but also the determination of antibody cross-reactivity against the apolipoproteins AI, AII and B.

Aminophenols↗

PubMed2002

New biomarker evidence of oxidative DNA damage in whole saliva from clinically healthy and periodontally diseased individuals.

BACKGROUND: There is an increasing body of evidence implicating reactive oxygen species in the pathogenesis of periodontal tissue destruction. 8-Hydroxy-deoxyguanosine (8-OHdG) is one of the most commonly used markers to evaluate oxidative damage in a number of disorders including chronic inflammatory diseases. The aim of the present study was to evaluate 8-OHdG levels in whole saliva of patients with periodontitis and to assess the changes after initial treatment. METHODS: Saliva samples were collected from 78 patients with untreated periodontitis and 17 healthy control subjects. Clinical parameters and levels of 8-OHdG were assessed first to establish a baseline and again after initial periodontal treatment from 15 patients. 8-OHdG levels were determined by enzyme-linked immunosorbent assay. RESULTS: The mean value of 8-OHdG in the saliva of periodontally diseased subjects, 4.28 +/- 0.10 ng/ml, was significantly higher (P<0.01) than that of clinically healthy subjects (1.56 +/- 0.10 ng/ml). A significant decrease in salivary 8-OHdG was observed after therapy (P<0.01). CONCLUSION: In the present study, we evaluated for the first time 8-OHdG levels in whole saliva of patients with periodontitis and assessed changes after initial periodontal treatment. Our study indicated that 8-OHdG levels in saliva appear to reflect the status of periodontal health.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1993

Psychotherapy during pregnancy: opportunities and challenges.

In this article, I emphasized the developmental receptivity of pregnant women to psychotherapeutic interventions. I selected four psychotherapy themes, illustrated with examples of brief, conflict-focused interventions with pregnant women and their families. The first theme that I discussed was conflicts over increased dependency needs, and I gave clinical examples of helping to express and to tolerate such needs. The second theme examined was narcissistic disturbances and pregnancy. I discussed both the impact of a burdening maternal ego ideal and the attempts to reestablish a narcissistic balance through pregnancy. In the third theme, reconciliative themes in pregnancy, I discussed the identificatory struggle with the mother's mother that is reactivated by pregnancy, both in renegotiating separation from her and in facing issues of rivalry. In the last theme, working through losses while giving life, I described a case of mourning during pregnancy. In the discussion, I examined various aspects of involving expectant fathers and other family members in treatment. Finally, I discussed various transference phenomena, including the fetus as a transference object, some aspects of the transference to the therapist, and the integration of different transference phenomena.

Adult↗

PubMed2004

A transitory homosexual passion in the course of an analytic treatment.

Do homosexualities express a sexual conflict originating in bisexuality or must we look for their deep determinism in the narcissistic conflict and its vicissitudes? Two clinical sequences from the treatment of a borderline patient, which occurred during years seven and eight of treatment, a period characterised by intense drive turbulence and the unexpected occurrence of a transitory homosexual passion, will enable the reader to follow the psychical movements and evolution of the work of representation. The first sequence throws light on the links between her sudden involvement in this homosexual passion and the traumatic dangers of a breakdown of her ego's capacity for representation, linked to a reactivation in the transference of early and later traumatic traces whose reverberation in the transfero/countertransference dynamic was the source of a painful transference that was responsible for this lateral transference movement. The second sequence shows the links between the strengthening of her capacity for representation, thanks to the working through of the oedipal conflict in its two aspects, and her renunciation of this passion. The roots of this transitory homosexual passion in the deep flaws of her psychical functioning raise metapsychological questions concerning, in particular the dynamic of the 'double' ('twin') and narcissism.

Adult↗

PubMed2001

High-resolution probing of local conformational changes in proteins by the use of multiple labeling: unfolding and self-assembly of human carbonic anhydrase II monitored by spin, fluorescent, and chemical reactivity probes.

Two different spin labels, N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl)iodoacetamide (IPSL) and (1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl) methanethiosulfonate (MTSSL), and two different fluorescent labels 5-((((2-iodoacetyl)amino)-ethyl)amino)naphtalene-1-sulfonic acid (IAEDANS) and 6-bromoacetyl-2-dimetylaminonaphtalene (BADAN), were attached to the introduced C79 in human carbonic anhydrase (HCA II) to probe local structural changes upon unfolding and aggregation. HCA II unfolds in a multi-step manner with an intermediate state populated between the native and unfolded states. The spin label IPSL and the fluorescent label IAEDANS reported on a substantial change in mobility and polarity at both unfolding transitions at a distance of 7.4-11.2 A from the backbone of position 79. The shorter and less flexible labels BADAN and MTSSL revealed less pronounced spectroscopic changes in the native-to-intermediate transition, 6.6-9.0 A from the backbone. At intermediate guanidine (Gu)-HCl concentrations the occurrence of soluble but irreversibly aggregated oligomeric protein was identified from refolding experiments. At approximately 1 M Gu-HCl the aggregation was found to be essentially complete. The size and structure of the aggregates could be varied by changing the protein concentration. EPR measurements and line-shape simulations together with fluorescence lifetime and anisotropy measurements provided a picture of the self-assembled protein as a disordered protein structure with a representation of both compact as well as dynamic and polar environments at the site of the molecular labels. This suggests that a partially folded intermediate of HCA II self-assembles by both local unfolding and intermolecular docking of the intermediates vicinal to position 79. The aggregates were determined to be 40-90 A in diameter depending on the experimental conditions and spectroscopic technique used.

Amino Acid Substitution↗

PubMed1993

Object relations issues in the treatment of the preoedipal character.

It was through tolerance of Ms. D.'s infantile rage (i.e., rage against reality and its limits) that the analyst was able to open up a dialogue with the patient that could lead to a developmental mourning process. The same was true for the borderline character, Ms. A.! The interpersonal dialogue between analyst and analysand, which had both empathic and interpretive functions, allowed Ms. D. to reactivate her capacities for an intrapsychic dialectic gained during infancy. In her case, as well as in that of Ms. A., the initiation of an internal dialectic allowed for a mourning process to unfold. It is proposed that this internal dialectic is evidence of the existence of the psychic structure necessary to promote both mourning and the mutuality of interpersonal dialogue. The inability to mourn, generally seen in narcissistic and borderline characters, can be seen, therefore, not only as a failure in psychic structure formation, but also as a failure in psychic structure function that is due to intrapsychic defense.

Adult↗

PubMed1991

Expression of a cell adhesion protein (VLA beta) in normal and diseased skin.

Biopsies from normal skin (n = 17) and various cutaneous disorders (n = 83) were examined immunohistologically for reactivity with an antibody (CD29) against the common beta chain of the VLA integrin family. In normal skin, CD29 recognized a number of cell types, i.e. endothelial cells, fibroblasts, T lymphocytes and basal keratinocytes. Similar cells were positive in diseased skin, but the expression of VLA beta was upregulated on keratinocytes. The phenotype of the VLA beta-positive T cells was examined in more detail by staining with anti-T-cell antibodies, i.e. CD3, CD4, CD8, CD45RO (UCHL1) and CD45R (2H4). These studies showed that most of the T cells in normal skin, benign cutaneous conditions and early cutaneous T-cell lymphomas (CTCL) expressed a similar phenotype and resembled antigen committed 'memory' (helper/inducer) cells (CD4+, CD29+, CD45RO+, CD45R-). In advanced CTCL, expression of these antigens was more variable, and many of these infiltrates showed aberrant (or unusual) expression of CD29, CD45RO, CD45R and other T-cell antigens. It is concluded that several cells involved in cutaneous immune reactions express a molecule (VLA beta) which acts as a receptor for extracellular matrix components. This molecule is important for the attachment of cells to connective tissue constituents and may act to facilitate the migration of lymphocytes (and other cells) during immune reactions in normal and diseased cutaneous conditions. Advanced CTCL differ from the early lesions and it is possible that there is a progressive accumulation of increasingly malignant (or transformed) cells in these conditions.

Antigens, CD↗