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PubMed1990

Reactive psychosis and mortality.

Reactive psychosis is generally thought of as a nosological term of favourable course and outcome. Studies of mortality risk following this psychosis are sparse and inconclusive. This study shows that using mortality as an index of outcome, first-admitted patients with reactive psychosis have as poor an outcome as patients with the endogenous psychoses schizophrenia and manic-depressive psychosis, and thus an excess mortality risk compared with that of the population in general. Reactive depressed patients have even a higher relative mortality risk than endogenous depressed patients. Certain precautions are attached to the use of diagnostic classification of first admissions and especially for reactive psychosis. But as this is a commonly used diagnostic term in Scandinavian psychiatry, the high relative mortality risk is notable. In the search for methods of prevention, the cause of death will be examined in future studies.

Bipolar Disorder↗

PubMed1989

Acupuncture as therapy of traumatic affective disorders and of phantom limb pain syndrome.

Functional isomorphism holds between four essential properties of acupuncture and of meditation, namely, 1) alpha rhythm prominent in electro-encephalograms (EEG); 2) deep general relaxation; 3) high degree of unresponsiveness to ordinarily painful stimuli; 4) participation of virtually the entire body. It is postulated, subject to experimental test, that a "stillness" prevails during acupuncture similar to the quiet of meditation. The quiet of meditation and by postulate, the "stillness" of acupuncture, provide high degree of unresponsiveness to aversive components of conditioned stimuli which had habitually reactivated affective trauma. This marked unresponsiveness accounts for the "stillness" and its EEG alpha rhythm. With its low noise level the "stillness" also provides the cerebral cortex better resolved, more intense signals relative to background and more comprehensive, clear information. The cortex can then call upon newly mobilizable, more precise regulation for removing imbalances throughout the body. The same factors apply to the therapy by acupuncture of phantom limb pain syndrome if the pain impulses from the limb, while attached, is the unconditioned stimulus of a reflex in which impulses from inner organs function as conditioned stimuli. Successful therapy of the syndrome using laser-stimulated acupuncture points is discussed accordingly. Emphasized is the desirability to maximize the "stillness," possibly by monitoring the course of therapy by displayed EEG.

Acupuncture Therapy↗

PubMed1994

Epidermolysis bullosa herpetiformis (Dowling-Meara type) exhibits ultrastructural derangement of tonofilaments and desmosomes.

Ultrastructural and immunohistochemical studies of clinically intact skin obtained from three severe neonatal cases of epidermolysis bullosa herpetiformis (Dowling-Meara type) demonstrated disorders in the assembly of keratin intermediate filaments and desmosomes of the keratinocytes. During mitosis, K5- and K14-positive and K1- and K10-negative tonofilaments were disrupted and formed spherical bodies associated with intracytoplasmic desmosomes by invagination of the desmosomes and the adjacent plasma membrane. During the invagination process, destructive changes in the internalized membrane were noted. These were accompanied by gradual loss of reactivity with a monoclonal antibody ZK31, which detected plasma membrane adjacent to the attachment plaques of desmosomes. However, the reactivity of the attachment plaques of the internalized desmosomes for desmoplakins and desmoglein did not decline during the process of internalization. In the suprabasal layers of the epidermis, filamentous substructures and K1 and K10 appeared at the periphery of the spherical bodies. Simultaneously, the desmosomes that were sparsely located in the lower epidermis, increased in number as cell differentiation progressed. Thus, the keratinocytes attained an almost normal appearance with respect to tonofilaments and desmosomes by the time they reached the upper layer of the epidermis. These findings may be relevant to the mechanism responsible for the clinical appearance of the herpetiform blisters in epidermolysis bullosa herpetiformis, which are also characterized by spontaneous involution during childhood or when exposed to high ambient temperatures.

Cell Membrane↗

PubMed2004

[Defense of living body against oxidative damage].

Living bodies may experience oxidative stress induced by reactive oxygen species and heavy metal ions, which may damage components in the body and cause aging and disorders. In addition to the known defense systems against oxidative damage, the author describes new defense systems. Lipid peroxidation in living bodies, which has hitherto been thought to increase oxidative damage, was found to attenuate oxidative stress-induced DNA damage. Red blood cells become senescent due to oxidative stress during circulation, where membrane band 3 becomes aggregated to anti-band 3 IgG and macrophages attached through poly-N-acetyllactosaminyl sugar chains, and the sugar chain attachment to macrophages is stimulated by oxidative stress in macrophages. Oxidized protein hydrolase that preferentially hydrolyzes proteins damaged by oxidative stress was newly discovered, which may play an important role in saving cells from oxidative damage.

Animals↗

PubMed1994

The cognition-enhancing drug tenilsetam is an inhibitor of protein crosslinking by advanced glycosylation.

Non-enzymatic glycosylation of proteins, also called Maillard reaction, which occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation endproducts (AGEs). Tenilsetam (CAS 997: (+/-)-3-(2-thienyl)-2-piperazinone), a cognition-enhancing drug successfully used for treatment of patients suffering from Alzheimer's disease, when included in the Maillard reaction apparently inhibits protein crosslinking by AGEs in vitro. According to the mechanism proposed, Tenilsetam acts via covalent attachment to glycated proteins, thus blocking the reactive sites for further polymerisation reactions. A beneficial effect of Tenilsetam in Alzheimer's disease could come from the interference with AGE-derived crosslinking of amyloid plaques and a decreased inflammatory response by diminished activation of phagocytosing microglia.

Aging↗

PubMed1997

Up-regulated beta1-integrin expression in autoimmune thyroid disorders.

Lymphocytic infiltration of the thyroid gland in autoimmune thyroid disorders requires, as a first step, their attachment to endothelial cells (EC) and, subsequently, interaction with thyrocytes and extracellular matrix proteins. Recent studies have focused on the pathophysiologic role of beta1-integrins as adhesion receptors for extracellular matrix proteins and as cell-to-cell adhesion receptors. In this study, we examine by flow cytometry and immunohistochemical techniques the differences in expression of beta1-integrins in thyrocytes and EC between normal thyroids and thyroid glands from patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). Remarkably, we found an up-regulated de novo expression of very late antigen (VLA)-alpha6 subunit in thyrocytes in close proximity to lymphocyte infiltrates in GD and HT thyroid glands, with no reactivity in control thyroids. Moreover, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-1beta produced a significant enhancement of VLA-alpha6 expression in vitro in thyrocytes in culture. In addition, an up-regulated expression of VLA-alpha5 and beta1 subunits was found in thyrocytes from GD and HT glands, specifically in those areas more severely inflamed. VLA-alpha2 was basally expressed in middle size and large vessels in control glands, with an increased expression in vessels of all sizes in HT and GD glands. Dendritic cells in thyroid lymphoid follicles were also positive for VLA-beta1, alpha2 and alpha6 subunits. These results indicate the existence of an up-regulatory process in the expression of beta1-integrins, particularly the alpha6 subunit, in several cell types from inflamed GD and HT thyroid glands, suggesting that these integrins could play a relevant role in localizing and perpetuating the autoimmune response in the thyroid gland in autoimmune thyroid disorders.

Adult↗

PubMed2003

Laboratory diagnosis of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired stem cell disorder associated with periodic hemolytic events. This benign clonal disease is caused by abnormalities of the X-linked phosphatidylinositol glycan class A (PIGA) gene and is associated with cytopenias and thrombosis. Although the trilineage of bone marrow elements is affected, involvement of the red blood cell (RBC) line was recognized first due to its abnormal sensitivity to complement-mediated intravascular hemolysis. Totally or partially deficient blood cell membrane proteins include decay accelerating factor (DAF, CD55), membrane inhibitor of reactive lysis (MIRL, CD59), and other proteins attached to the glycophosphatidylinositol (GPI) spine. Stem cell transplantation can be curative in PNH. Diverse laboratory abnormalities observed in PNH include bone marrow hyper- and hypoplasia, hematologic cytopenias, micro- and macrocytosis, decreased leukocyte alkaline phosphatase (LAP), hemoglobin- and hemosiderinuria, as well as associated iron deficiency. The more definitive laboratory tests comprise older biochemical and newer flow cytometric (FCM) procedures. The former group includes the sucrose hemolysis test for screening and Ham's acid hemolysis test for confirmation; the latter group includes FCM analyses of CD55 and CD59, which have recently replaced Ham's test, and FCM quantification of specific GPI-anchor binding using fluorescent-labeled inactive toxin aerolysin (FLAER). FLAER is more sensitive than FCM quantification of antibody-binding to CD59 for PNH diagnosis.

Clinical Laboratory Techniques↗

PubMed1997

[Internal representation of diseased organs and symbolic disguise of conflictual object relations].

Psychoanalytic-psychosomatic hypotheses assume, among other things, that patients with psychosomatic diseases tend to represent conflict-laden object relationship experiences symbolically in the diseased organ of the body. This assertion was tested on 139 patients having inflammatory and irritable bowel diseases with the help of the repertory grid technique. Univariate analysis showed that this hypothesis not only applies to the primary object, but is also valid for the partner relationship. Neither gender nor illness behaviour affect the connections observed here. Although patients with irritable bowel diseases as well as those suffering from Crohn's disease or colitis ulcerosa, have differing pathogeneses, there is a comparable tendency in all three diagnostic groups to represent object relationships leaded with conflict symbolically in the diseased organ of the body. The finding that the physical and psychological condition of the moment in the sense of a reactive component like-wise has to intervening influence, leads to the supposition that, in accordance with theoretical assumptions, this is a general factor.

Adult↗

PubMed1999

Psoralen photo-cross-linking by triplex-forming oligonucleotides at multiple sites in the human rhodopsin gene.

Targeting DNA damage by triplex-forming oligonucleotides (TFOs) represents a way of modifying gene expression and structure and a possible approach to gene therapy. We have determined that this approach can deliver damage with great specificity to sites in the human gene for the G-protein-linked receptor rhodopsin, mutations of which can lead to the genetic disorder autosomal dominant retinitis pigmentosa. We have introduced DNA monoadducts and interstrand cross-links at multiple target sites within the gene using TFOs with a photoactivatable psoralen group at the 5'-end. The extent of formation of photoadducts (i.e., monoadducts and cross-links) was measured at target sites with a 5'-ApT sequence at the triplex-duplex junction and at a target site with 5'-ApT and 5'-TpA sequences located four and seven nucleotides away, respectively. To improve psoralen reactivity at more distant sites, psoralen moieties were attached to TFOs with nucleotide "linkers" from two to nine nucleotides in length. High-affinity binding was maintained with linkers of up to 10 nucleotides, but affinities tended to decrease somewhat with increasing linker length due to faster dissociation kinetics. DNase I footprinting indicated little, if any, interaction between linkers and the duplex. Psoralen-TFO conjugates formed DNA cross-links with high efficiency (56-65%) at 5'-ApT sequences located at triplex junctions. At a 5'-ApT site four nucleotides away, the efficiency varied with linker length; a four-nucleotide linker gave the highest efficiency. Duplexes with 5'-TpA and 5'-ApT sites two nucleotides away, in otherwise identical sequences, were cross-linked with efficiencies of 56 and 38%, respectively. These results indicate that TFO-linker-psoralen conjugates allow simultaneous, efficient targeting of multiple sites in the human rhodopsin gene.

Base Sequence↗

PubMed2004

Clarifying parent-child reciprocities during early childhood: the early childhood coercion model.

Consistent with existing theory, the quality of parent-child interactions during early childhood affects children's social relationships and behavioral adjustment during middle childhood and adolescence. Harsh parenting and a propensity toward emotional overarousal interact very early in life to affect risk for later conduct problems. Less empirical work has evaluated the emergence of early childhood coercive parent-child reciprocities. The proposed early childhood coercion model describes the processes by which coercive parent-child reciprocities emerge. Specifically, the interaction between parenting and infants' propensities toward reactivity influences the development of emotion regulation in children and disciplinary styles in parents. Highly reactive children are expected to experience more difficulty learning to regulate emotions and to evoke harsher parenting. Through a process of mutual reinforcement, harsh parenting, negative emotional reactivity, and poor emotion regulation become coercive parent-child reciprocities during early childhood. The emergence of coercive parent-child interactions further diminishes children's emotional regulatory capacities and affects the formation of peer relationships during kindergarten.

Adult↗

PubMed1986

Comparison of spindle elongation in vivo and in vitro in Stephanopyxis turris.

The spindle in dividing cells of the diatom Stephanopyxis turris contains three distinct classes of microtubules: central spindle microtubules, which slide over each other and grow during anaphase spindle elongation; kinetochore-attached microtubules, which are located on the outer surface of the central spindle; and peripheral microtubules, which fan out from the spindle poles in astral-like arrays. The poles are multilayered structures, which remain attached to the spindle after isolation. In vitro, after addition of ATP, central spindles elongate and the two half-spindles slide completely apart with a concurrent decrease in the extent and magnitude of the zone of microtubule overlap. Spindle elongation takes place in spindles whose chromatin has been removed by enzymic digestion and the extent of elongation in vitro is increased by the addition of neurotubulin. After ATP addition the arrays of interdigitating microtubules in the zone of overlap become disordered and selectively depolymerize from the overlap zone polewards. In some reactivated spindles an unusual structure, a striated fibre, can be seen running from the pole plates part of the way towards the spindle midzone. The fibre has no precedent in mitotic ultrastructure and its function is unclear. These results demonstrate that we can duplicate the essential elements of anaphase B in vitro and that this system will be useful for further studies of the molecular basis of spindle elongation.

Anaphase↗

PubMed1984

[Significance of object loss on the course of psychosomatic diseases].

Psychosomatic diseases are organic diseases in the pathogenesis of which a psychic factor has an important significance. They are no nosological unit. Psychotherapeutic experience with such patients causes us to search for the different measure of this psychic disturbance. The authors deal with the research on narcissism and object loss which has again been performed since 10 years. The psychosomatic patient has difficulties with overcoming discouraging events (object losses) which evoke a depressive reaction in him. Pathophysiological connections between the reactive depression and the organic lesion are discussed. The psychotherapy has a double task: actual influence on the depressive reaction as well as the aid of learning a more suitable form of explanation of the discouragement.

Adolescent↗

PubMed1989

Bernard-Soulier syndrome.

Bernard-Soulier syndrome (BSS) is a rare autosomal bleeding disorder characterized clinically by prolonged skin bleeding time, normal clot retraction and thrombocytopenia with large and morphologically abnormal platelets, and biochemically by the absence of platelet membrane glycoproteins (GP) Ib, V and IX. GP Ib and GP IX exist in the platelet membrane as a heterodimer complex which acts as the major receptor mediating platelet adhesion to blood vessel subendothelium. Studies with BSS platelets have proved particularly rewarding in the investigation of the GP Ib-IX complex as a multifunctional receptor protein. The transmembrane complex contains binding domains for von Willebrand factor, thrombin, fibrin and quinine/quinidine drug-dependent antibodies as well as an attachment site on the cytoplasmic side of the membrane for a platelet cytoskeleton. In addition, the internal segment of the beta-chain of GP Ib contains a cyclic AMP-dependent protein kinase-associated phosphorylation site which appears to regulate platelet reactivity. Limited proteolytic cleavage of the complex, in particular the GP Ib alpha-chain, has allowed immunological and functional characterization of three distinct domains; a 45 kDa segment at the N-terminal end of the alpha-chain of GP Ib, which contains binding sites for von Willebrand factor and thrombin, a 90 kDa highly glycosylated region of GP Ib alpha and a membrane-associated region consisting of the remnant of GP Ib alpha disulphide-linked to GP Ib beta and non-covalently-complexed with GP IX. This membrane-associated region contains the antigenic epitope(s) for quinine/quinidine drug-dependent antibodies. It is highly probable that the future study of platelets from patients with the Bernard-Soulier syndrome will further clarify the role of the GP Ib-IX complex in platelet physiology.

Bernard-Soulier Syndrome↗

PubMed1992

[Psychosomatic disorder, psychosis and object relations].

This paper presents a case who successively suffered from regional ileitis followed by a reactive psychosis. The author looks at the object relations of a patient afflicted by a narcissistic defect. The fundamental narcissistic disorder models the object relations of the somatic patient and of the psychotic patient. Less differentiation is found in the object representation of the psychotic patient. A comparison is suggested for the two modes of relating to objects.

Adult↗

PubMed2006

Simulated data sets for single molecule kinetics: some limitations and complications of data analysis.

When the fluorescence intensity of a chromophore attached to or bound in an enzyme relates to a specific reactive step in the enzymatic reaction, a single molecule fluorescence study of the process reveals a time sequence in the fluorescence emission that can be analyzed to derive kinetic and mechanistic information. Reports of various experimental results and corresponding theoretical studies have provided a basis for interpreting these data and understanding the methodology. We have found it useful to parallel experiments with Monte Carlo simulations of potential models hypothesized to describe the reaction kinetics. The simulations can be adapted to include experimental limitations, such as limited data sets, and complexities such as dynamic disorder, where reaction rates appear to change over time. By using models that are known a priori, the simulations reveal some of the challenges of interpreting finite single-molecule data sets by employing various statistical signatures that have been identified.

Data Interpretation, Statistical↗

PubMed1994

Adhesion molecules from the LFA-1/ICAM-1,3 and VLA-4/VCAM-1 pathways on T lymphocytes and vascular endothelium in Graves' and Hashimoto's thyroid glands.

Lymphocytic infiltration of the thyroid gland in autoimmune thyroid disorders requires, as a first step, their attachment to endothelial cells (EC) and subsequently, their interaction with thyrocytes and extracellular matrix proteins. A number of different ligand molecules have been identified to mediate the interaction between EC and leukocyte subpopulations. In this study, we examined by flow cytometry and immunohistochemical techniques, the expression of integrin receptors and their counter-receptors by infiltrating lymphocytes and vascular endothelium in thyroid glands from patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). A high proportion of GD intrathyroidal T lymphocytes expressed the CD69 and gp95/85 (Ea2) activation antigens as well as an increased number of LFA-alpha L, VLA-alpha 1, -alpha 4, -alpha 5, and beta 1 integrin receptors, as compared with peripheral blood T lymphocytes from the same patients. The expression of intercellular adhesion molecule (ICAM)-1 was increased in EC from GD and HT thyroids. In addition, an up-regulated de novo expression of vascular cell adhesion molecule (VCAM)-1 was found in EC in GD and HT thyroids, with no reactivity in control thyroids. Dendritic cells in thyroid lymphoid follicles were also positive for ICAM-1 and VCAM-1. In addition, most of intrathyroidal mononuclear cells expressed the ICAM-3 adhesion molecule. This enhanced expression of ICAM-1 and VCAM-1 by thyroid EC in GD and HT may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules. Our data suggest that both the LFA-1/ICAM-1, ICAM-3 and VLA-4/VCAM-1 pathways could play a relevant role in localizing and perpetuating the autoimmune response in the thyroid gland in autoimmune thyroid disorders.

Antigens, CD↗

PubMed2005

Cognitive reactivity and vulnerability: empirical evaluation of construct activation and cognitive diatheses in unipolar depression.

Cognitive vulnerability is a central concept in cognitive theories of unipolar depression. This idea suggests that negative cognitive factors emerge during stressful situations, and that this cognitive reactivity is critical for the onset, relapse, and recurrence of depression. The number of empirical investigations that model the diathesis-stress nature of cognitive reactivity has substantially increased within the last decade. This review examines this literature, with a focus on priming and longitudinal designs. Extant research supports the concept of cognitive vulnerability to depression among adults, and support is accruing for the validity of this concept among children. Research that examines direct links between cognitive vulnerability and depression onset, relapse, and recurrence and the attachment origins of cognitive vulnerability is also accruing, although at a slower pace.

Cognition Disorders↗

PubMed1984

Crossbridge order and orientation in resting single glycerinated muscle fibres studied by linear dichroism of bound rhodamine labels.

Linear dichroism of iodoacetyl-rhodamine labels attached to the highly reactive thiol of the myosin heads was measured in order to infer the spatial orientation and the degree of order in myosin crossbridges in single glycerinated rabbit psoas fibres at rest. We have previously shown that in rigor the chromophoric labels are well ordered and that in the presence of MgADP and during isometric contraction a large fraction of probes is also ordered but at an attitude different from that of rigor. Here we show that in relaxed muscle the probe order is dependent on total ionic strength: at and above 0.180 M there is little evidence for any preferred probe orientation, implying a high degree of crossbridge disorder. Below 0.160 M there is progressively more order with decreasing ionic strength down to 0.100 M, below which no measurements could be taken at room temperature (because the fibres would not relax). The dichroism observed under these conditions resembles that of the rigor state in that the dichroism peaks at the same polarization of excitation light, implying that the average probe attitude relative to the fibre axis is larger than 54.7 degrees. Stretching the muscle beyond the point of overlap between actin- and myosin-containing filaments does not affect the ionic strength dependence of the amount of order present in relaxed muscle, suggesting that the observed order is due to ionic interactions of crossbridges with the thick filament surface.

Animals↗