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Development of an integrated model of personality, personality disorders and severe axis I disorders, with special reference to major affective disorders.

A unidimensional model of the relationships between normal temperament, psychopathic variants of it and the two main forms of so-called endogenous psychoses (major affective disorders and schizophrenia) was derived from Kretschmer's constitutional typology. It was, however, not confirmed by means of a biometric approach nor was Kretschmer's broad concept of cyclothymia as a correlate of physical stoutness on the one hand and major affective disorders on the other supported by empirical data. Yet the concept of the 'melancholic type' of personality of patients with severe unipolar major depression (melancholia) which resembles descriptions by psychoanalysts could be corroborated. This was also true for the 'manic type' of personality as a (premorbid) correlate of predominantly manic forms of a bipolar I disorder. As predicted from a spectrum concept of major affective disorders, the ratio of traits of either type co-varied with the ratio of the depressive and the manic components in the long-term course of such a disorder. The two types of premorbid personality and a rare variant of the 'manic type', named 'relaxed, easy-going type', were conceived as 'affective types' dominating in major affective disorders. They are opposed to three 'neurotoid types' prevailing in so-called neurotic disorders as well as in schizophrenic psychoses. The similarity among the types can be visualized as spatial relationships in a circular, i.e. a two-dimensional, model (circumplex). Personality disorders as maladapted extreme variants of personality are, by definition, located outside the circle, mainly along its 'neurotoid' side. However, due to their transitional nature, axis I disorders cannot be represented adequately within the plane which represents (adapted as well as maladapted) forms of habitual behaviour (personality types and disorders, respectively). To integrate them into the spatial model of similarity interrelations, a dimension of actual psychopathology has to be added to the two-dimensional plane as a third (orthogonal) axis. The distance of a case from the 'ground level' of habitual behaviour corresponds with the severity of the actual psychopathological state. The specific form of that state (e.g. manic or depressive), however, varies along one the axes which define the circumplex of habitual behaviour. This three-dimensional model is, by its very nature, more complex than the unidimensional one derived from Kretschmer's typological concept, but it is clearly more in accordance with empirical data.

Affective Disorders, Psychotic↗

Postnatal functional development of the dorsal and posteroventral cochlear nuclei of the cat.

The postnatal development of firing patterns and response areas was determined for single neurons in the dorsal (DCN) and posteroventral ( PVCN ) cochlear nuclei of the kitten. Extracellular, single-unit responses to pure-tone stimulation were recorded in ketamine and sodium pentobarbital anesthetized kittens between the ages of 5 and 52 days. Within the first two weeks of postnatal life threshold is high, first-spike latency is long, and maximal discharge rate is low as compared to older kittens and adult cats. Prior to the end of the second postnatal week the tone-evoked temporal discharge patterns that characterize neurons of the DCN and PVCN in the adult cat are routinely recorded. These patterns, which appear within the first 50 ms of tonal stimulation, include the so-called " primarylike ," "chopper," " pauser ," "buildup," and "onset" types and their variants. In animals younger than about 10-12 days of age, the driven activity that occurs later than about 50 ms after stimulus onset often is not sustained, but breaks up during the stimulus into bursts that are separated by intervals of about 100-150 ms. Also within the first two weeks of postnatal life, many of the response-area properties of DCN and PVCN neurons are similar to those recorded in adult cats. The excitation and inhibition found within the so-called type II/III, type IV, and type V response areas of the adult occur in this early postnatal period. We conclude that many of the cellular mechanisms that underlie the temporal firing patterns and the organization of the response areas of DCN and PVCN neurons are active in the growing, differentiating cochlear nuclei and that the emergence of these mechanisms does not depend on afferent activity generated in the cochlear and auditory nerve by the animal's acoustic environment. Furthermore, if temporal firing patterns and response-area profiles remain relatively constant over the life span of the animal, then so must the spatial and temporal relationships of the inputs that produce and maintain them as these neurons, and the circuits of which they are a part, grow in size and complexity.

Action Potentials↗

The opacity proteins of Neisseria gonorrhoeae strain MS11 are encoded by a family of 11 complete genes.

Variants of Neisseria gonorrhoeae MS11 show distinct colony morphologies because of the expression of a class of surface components called opacity (Opa, PII) proteins. Southern analyses combined with molecular cloning of genomic DNA from a single variant of MS11 has identified 11 opa genes contained in separate loci. These opa genes code for distinct opacity proteins which are distinguishable at their variable domains. The opa gene analyses were also extended to divergent variants of MS11. These studies have shown that, during in vitro and in vivo culture, 10 of the 11 opa genes did not undergo significant change in their primary sequence. However, in these variants, one gene (opaE) underwent non-reciprocal inter-opa recombinations to generate newer Opa variants. Phylogenic analysis of the opa gene sequences suggests that the opa gene family have evolved by a combination of gene duplication, gene replacement and partial inter-opa recombination events.

Amino Acid Sequence↗

Expression of polypeptide variants of receptor-type protein tyrosine phosphatase beta: the secreted form, phosphacan, increases dramatically during embryonic development and modulates glial cell behavior in vitro.

Glial cells express three splicing variants of a receptor-type protein tyrosine phosphatase called RPTP beta. Two are receptor forms that differ in a large extracellular domain. The third is a secreted proteoglycan called phosphacan that lacks the cytoplasmic phosphatase domains. We have now identified, by immunoblotting, proteins corresponding to these three forms of RPTP beta in rat C6 glioma cells and brain. The short receptor form is much more prevalent than the full-length receptor in C6 glioma cells. Phosphacan is much more abundant than either of the receptor forms in rat brain, and its expression increases progressively during embryonic development, while the receptor forms show only moderate changes. In contrast to the long form and phosphacan that were detected as proteoglycans, the short receptor form, lacking the large alternatively spliced domain, was not detected as a chondroitin sulfate proteoglycan. We recently showed that phosphacan binds to the neuron-glia cell adhesion molecule, Ng-CAM, and we now report that glia expressing RPTP beta adhere and extend processes on substrates coated with Ng-CAM. After one day in culture, however, the glia retract their processes and often lift off the substrate. Conditioned medium from glial cells, which contains large amounts of phosphacan, inhibits glial adhesion to Ng-CAM, and depletion of phosphacan from the conditioned medium by immunoadsorption reduces the inhibitory activity. The results show that phosphacan increases dramatically during development, and indicate that secreted forms of RPTP beta can modulate glial cell adhesion and behavior.

Animals↗

On the (dis) advantages of cannibalism.

Cannibalism is an interaction between individuals that can produce counter- intuitive effects at the population level. A striking effect is that a population may persist under food conditions such that the non-cannibalistic variant is doomed to go extinct. This so-called life boat mechanism has received considerable attention. Implicitly, such studies sometimes suggest, that the life boat mechanism procures an evolutionary advantage to the cannibalistic trait. Here we compare, in the context of a size structured population model, the conditions under which the life boat mechanism works, with those that guarantee, that a cannibalistic mutant can invade successfully under the steady environmental conditions as set by a non-cannibalistic resident. We find qualitative agreement and quantitative difference. In particular, we find that a prerequisite for the life boat mechanism is, that cannibalistic mutants are successful invaders. Roughly speaking, our results show that cannibalism brings advantages to both the individuals and the population when adult food is limiting.

Animals↗

Syndrome stability and psychological predictors of symptom severity in idiopathic environmental intolerance and somatoform disorders.

BACKGROUND: Previous studies suggest that idiopathic environmental intolerance (IEI) is a variant of somatoform disorders (SFDs) or the so-called functional somatic syndromes. Little is known, however, about the stability and the psychological predictors of IEI. METHOD: This prospective study examined the 1-year stability of somatic symptoms and IEI features in three diagnostic groups: 49 subjects with IEI, 43 subjects with SFD but without IEI, and 54 subjects (control group, CG) with neither IEI nor SFD. The predictive value of typical psychological predictors for somatization was tested using zero-order correlations and multiple linear regression analyses. RESULTS: Somatic symptoms and IEI features proved to be temporally stable over the 1-year follow-up period. The SFD and IEI groups scored significantly higher than CG on all measures of somatic symptoms and on questionnaires assessing psychological predictors for somatization. Measures of trait negative affectivity (NA), somatic symptom attribution and somatosensory amplification predicted somatic symptom severity within the IEI and SFD groups, both at baseline and 1 year later. The strongest predictors of IEI complaints in the IEI group were somatic attributions, followed by prominent cognitions of environmental threat and a tendency to focus on unpleasant bodily sensations and to consider them as pathological. CONCLUSIONS: IEI and SFD are highly stable conditions. In both SFD and IEI, NA and the processes of symptom perception, interpretation and attribution contribute substantially to the persistence of typically somatoform symptoms and IEI complaints. Treatment of IEI and SFD should address these psychological factors and mechanisms.

Adult↗

An unusual translocation of immunoglobulin gene segments in variants of the mouse myeloma MPC11.

Immunoglobulin light chain genes of the mouse are composed in germ-line DNA of four separate segments, the leader, V (variable), J (joining) and C (constant) segments. In immunocompetent cells a V and J gene segment are joined by a site-specific recombination event. In variants of the mouse myeloma MPC11 a so-called kappa (k) light chain fragment is expressed which consists of the MOPC321 leader peptide, joined to the kappa constant region peptide. Using the Southern blotting technique we found that the gene coding for the light chain fragment has apkparently been generated by an aberrant translocation of a V gene segment identical or very similar to the MOPC321 V gene segment into the large intervening sequence between the J and the C gene segments. The resulting deletion of the splice signals of the J segments could be the reason for the observed splicing between leader and C region sequences, a phenomenon which may be of general interest for the understanding of the splicing mechanism.

Animals↗

The rise and fall of malignant fibrous histiocytoma.

The term malignant fibrous histiocytoma was coined by Stout and associates in the 1960s to encompass pleomorphic soft tissue sarcomas presumably derived from histiocytes that are capable of fibroblastic transformation. The concept was reaffirmed in the following 2 decades and malignant fibrous histiocytoma thus was regarded as the most common soft tissue tumor in older adults. However, recent more critical clinicopathologic, ultrastructural, and immunohistochemical studies have shown that malignant fibrous histiocytomas are not derived from histiocytic "facultative fibroblasts" and many neoplasms so diagnosed actually are pleomorphic subtypes of other sarcomas. Meticulous electron microscopic and immunohistochemical investigations also found that the more common storiform-pleomorphic, myxoid, and perhaps the giant cell subtypes are composed of variable mixtures of fibroblasts and phenotypically modulated fibroblastic cells, notably myofibroblasts and histiofibroblasts. On the basis of these findings, we propose a new classification for the above subtypes of so-called malignant fibrous histiocytoma, the majority of which are variants of pleomorphic fibrosarcoma.

Fibroblasts↗

Molecular characterization and expression of vitellogenin receptor from white perch (Morone americana).

A full-length (4021 base pair [bp]) cDNA encoding a polypeptide (844 amino acids) with a predicted mass of 93 kDa and other characteristic structural features of a vertebrate vitellogenin receptor (VgR) was isolated from a white perch (Morone americana) ovarian cDNA library. Northern blotting performed using a specific digoxygenin-labeled VgR cDNA probe revealed a distinct approximately 4.1 kilobase (kb) hybridization signal in an mRNA preparation obtained from previtellogenic perch ovaries. The deduced amino acid sequence of the perch VgR was 89% and 82% identical, respectively, to that of the tilapia and rainbow trout. Because it possessed an eight-repeat ligand-binding domain (LR8) but lacked an O-linked sugar domain (-), the perch VgR was identified as a non-O-linked form of VgR (LR8-). Unlike the case in other vertebrates investigated, including tilapia and trout, no species of mRNA encoding an O-linked form of VgR (LR8+) could be detected when perch ovarian or liver mRNA reverse transcripts or cDNA libraries were screened by PCR using primer sets flanking the putative O-linked sugar domain. These novel findings call into question the assumptions that an LR8+ splice variant of the VgR always is dominantly present in somatic tissues and exists at lower levels in ovarian tissues to sequester lipoproteins distinct from Vg. A SYBR-green-based real-time reverse transcription-polymerase chain reaction assay was developed and used to quantitatively measure VgR expression in gonadal and somatic tissues, for the first time in any vertebrate. The main site of perch VgR mRNA expression was the ovary and the highest level of VgR mRNA expression was in ovaries whose largest follicles contained previtellogenic oocytes. Expression of VgR mRNA decreased with oocyte growth during vitellogenesis and was very limited in ovulated eggs. These quantitative results verify the concept that growing oocytes must extensively recycle LR8- forms of the VgR.

Alternative Splicing↗

Vaccination against contagious bovine pleuropneumonia and the use of molecular tools in epidemiology.

Contagious bovine pleuropneumonia is a serious threat to cattle not only in Africa but also in southern Europe and possibly Asia. It is now present in countries that had been free of the disease for many years, giving rise to doubts about the efficiency of the control strategies. In Africa CBPP is controlled mainly by a vaccination policy that uses variant strains of Mycoplasma mycoides subsp mycoides biotype SC, called T1/44 or T1sr. Until recently, it was not possible to differentiate the various strains within the biotype and consequently to identify the vaccine strains. Restriction analysis of mycoplasma DNA with HindIII and Pst1 has been applied to 24 strains of African origin and one European strain. Each enzyme gave rise to different restriction profiles and the combination of the results permitted subdivision of these strains into 9 groups. Interestingly, some profiles of pathogenic strains seem to be restricted to certain geographical areas. The profile of the poorly immunogenic vaccinal strain KH3J is also very peculiar, and it is easily distinguished from that of the other vaccine strains originating from T1. This technique is simple once the strains are isolated. Efforts are now under way to use molecular tools based on PCR products to alleviate the difficulty of isolation.

Africa↗

The discrimination of baboon grunt calls and human vowel sounds by baboons.

The ability of baboons to discriminate changes in the formant structures of a synthetic baboon grunt call and an acoustically similar human vowel (/epsilon/) was examined to determine how comparable baboons are to humans in discriminating small changes in vowel sounds, and whether or not any species-specific advantage in discriminability might exist when baboons discriminate their own vocalizations. Baboons were trained to press and hold down a lever to produce a pulsed train of a standard sound (e.g., /epsilon/ or a baboon grunt call), and to release the lever only when a variant of the sound occurred. Synthetic variants of each sound had the same first and third through fifth formants (F1 and F3-5), but varied in the location of the second formant (F2). Thresholds for F2 frequency changes were 55 and 67 Hz for the grunt and vowel stimuli, respectively, and were not statistically different from one another. Baboons discriminated changes in vowel formant structures comparable to those discriminated by humans. No distinct advantages in discrimination performances were observed when the baboons discriminated these synthetic grunt vocalizations.

Animals↗

Immunohistochemical detection of alpha1E voltage-gated Ca(2+) channel isoforms in cerebellum, INS-1 cells, and neuroendocrine cells of the digestive system.

Polyclonal antibodies were raised against a common and a specific epitope present only in longer alpha1E isoforms of voltage-gated Ca(2+) channels, yielding an "anti-E-com" and an "anti-E-spec" serum, respectively. The specificity of both sera was established by immunocytochemistry and immunoblotting using stably transfected HEK-293 cells or membrane proteins derived from them. Cells from the insulinoma cell line INS-1, tissue sections from cerebellum, and representative regions of gastrointestinal tract were stained immunocytochemically. INS-1 cells expressed an alpha1E splice variant with a longer carboxy terminus, the so-called alpha1Ee isoform. Similarily, in rat cerebellum, which was used as a reference system, the anti-E-spec serum stained somata and dendrites of Purkinje cells. Only faint staining was seen throughout the cerebellar granule cell layer. After prolonged incubation times, neurons of the molecular layer were stained by anti-E-com, suggesting that a shorter alpha1E isoform is expressed at a lower protein density. In human gastrointestinal tract, endocrine cells of the antral mucosa (stomach), small and large intestine, and islets of Langerhans were stained by the anti-E-spec serum. In addition, staining by the anti-E-spec serum was observed in Paneth cells and in the smooth muscle cell layer of the lamina muscularis mucosae. We conclude that the longer alpha1Ee isoform is expressed in neuroendocrine cells of the digestive system and that, in pancreas, alpha1Ee expression is restricted to the neuroendocrine part, the islets of Langerhans. alpha1E therefore appears to be a common voltage-gated Ca(2+) channel linked to neuroendocrine and related systems of the body.

Animals↗

Dysphagia in a patient with lupus and review of the literature.

Dysphagia is not infrequent in patients with connective tissue diseases such as scleroderma, polymyositis or systemic lupus erythematosus (SLE). It is usually the result of gastro-oesophageal reflux but dysmotility can equally be responsible. A case of dysphagia is described in a patient with SLE, who had developed a rare variety of bullous mucous disease affecting the whole length of oesophagus with spontaneous extrusion of an oesophageal cast. Histological features were suggestive of a variant of rare form of bullous disease in SLE called epidermolysis bullosa acquisita (EBA). This rare association of SLE and EBA involving the oesophagus has not been described in the literature.

Adult↗

A novel isoform of human Golgi complex-localized glycoprotein-1 (also known as E-selectin ligand-1, MG-160 and cysteine-rich fibroblast growth factor receptor) targets differential subcellular localization.

The initial step in trafficking of leukocytes through the vascular endothelium is mediated by an adhesive interaction between molecules of the selectin family and their cognate receptors. Previously, a putative murine E-selectin ligand-1 (ESL-1) was identified and found to be identical to Golgi complex-localized glycoprotein-1 (GLG1), also known as MG-160, and to a previously identified basic fibroblast growth factor (bFGF)-binding protein known as cysteine-rich FGF receptor (CFR). We report here a novel variant of the human GLG1 gene product that we call GLG2, cloned from a human monocyte cDNA library. GLG2 encodes a polypeptide identical to GLG1 except with a unique 24-amino-acid extension at the C-terminus of its cytoplasmic domain. Transfection of chimeric constructs into human embryonic kidney epithelial 293 cells revealed that the cytoplasmic domains of GLG1 and GLG2 targeted the expression of each chimeric protein differentially, GLG1 to the cell surface and GLG2 to the Golgi. Genetic analysis suggests that GLG1 and GLG2 are the products of a single gene, the mRNA of which can be processed by alternative splicing to generate two different transcripts encoding either GLG1 or GLG2. Northern blot analysis showed that the relative amounts of the mRNAs for either isoform differ in a cell- and species-specific manner. These data suggest that alternative splicing of the GLG1 gene transcript might regulate the function of its product.

Alternative Splicing↗

Synchronous primary carcinomas of the ampulla of Vater and ascending colon in a patient with multiple flat adenomas.

Multiple primary cancers occurring in the same patients have been reported to represent 1.8-3.9% of all cancers. The majority of all patients reported to have had a combination of simultaneous neoplastic changes in the ampulla of Vater and the colon showed familial adenomatous polyposis (FAP) syndrome. Variants of familial adenomatous polyposis coli are: attenuated adenomatous polyposis coli (AAPC, previously also known as flat adenoma syndrome) and multiple adenoma coli. AAPC is characterized clinically by many, but usually fewer than 100, colonic lesions that are characteristically slightly elevated and plaque-like, with a reddish surface and sometimes central depression. Genetically it represents an extremely rare variant of FAP. Another group of individuals, so-called multiple adenoma patients, have a phenotype similar to AAPC, but most have no demonstrable germ-line adenomatous polyposis coli mutation, as do patients with FAP or AAPC. However, there have been only a few reports that discussed concurrent neoplastic changes in the ampulla of Vater and colon in patients with multiple colonic flat adenomas, but without the florid phenotype of classical FAP. We present rare clinical course of a patient with multiple (more than 60) flat adenomas in the proximal colon and two primary cancers: of the ampulla of Vater and of the ascending colon. This patient and his family history did not show polyposis compatible with FAP or hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.

Adenomatous Polyposis Coli↗

Solving combinatorial problems: the 15-puzzle.

We present a series of experiments in which human subjects were tested with a well-known combinatorial problem called the 15-puzzle and in different-sized variants of this puzzle. Subjects can solve these puzzles reliably by systematically building a solution path, without performing much search and without using distances among the states of the problem. The computational complexity of the underlying mental mechanisms is very low. We formulated a computational model of the underlying cognitive processes on the basis of our results. This model applied a pyramid algorithm to individual stages of each problem. The model's performance proved to be quite similar to the subjects' performance.

Humans↗

[How I treat ... idiopathic hyperhidrosis].

Palmo-plantar and/or axillary idiopathic hyperhidrosis is unpleasant and sometimes invalidating. Its malodorous variant which is due to biodegradation by bacterias is called bromhidrosis. According to the severity of the condition, several therapies exist including psychotherapy, various topical products, iontophoresis, botulinic toxin injections and thoracic sympathectomy.

Administration, Topical↗