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Showing papers by "Utrecht University published in 1992"



Journal ArticleDOI
TL;DR: This review is designed to critically examine relations between structure and function of the different compounds categorized as mucin glycoproteins.
Abstract: Considerable advances have been made in recent years in our understanding of the biochemistry of mucin-type glycoproteins. This class of compounds is characterized mainly by a high level of O-linked oligosaccharides. Initially, the glycoproteins were solely known as the major constituents of mucus. Recent studies have shown that mucins from the gastrointestinal tract, lungs, salivary glands, sweat glands, breast, and tumor cells are structurally related to high-molecular-weight glycoproteins, which are produced by epithelial cells as membrane proteins. During mucin synthesis, an orchestrated sequence of events results in giant molecules of Mr 4 to 6 x 10(6), which are stored in mucous granules until secretion. Once secreted, mucin forms a barrier, not only to protect the delicate epithelial cells against the extracellular environment, but also to select substances for binding and uptake by these epithelia. This review is designed to critically examine relations between structure and function of the different compounds categorized as mucin glycoproteins.

879 citations



Journal ArticleDOI
TL;DR: In this article, a scheme is presented that makes it possible to classify a large number of organic pollutants into one of four classes, viz: inert chemicals, less inert, reactive and specifically acting chemicals.

741 citations


Journal ArticleDOI
TL;DR: An overview of theory and experiments on liquid crystal phases which appear in solutions of elongated colloidal particles or stiff polymers is given in this article, along with extensions to polydisperse solutions and soft interactions.
Abstract: An overview is given of theory and experiments on liquid crystal phases which appear in solutions of elongated colloidal particles or stiff polymers. The Onsager (1949) virial thecry for the isotropionematic transition of thin rodlike particles is treated comprehensively along with extensions to polydisperse solutions and soft interactions. Computer simulations of liquid crystal phases in hard particle fluids are summarized and used to assess the quality of statistical mechanical thwries for stiff panicles at higher dume haion-like the inclusion of higher Virial coefficients, yexpansion, scaled particle theory and density functional theory. Both computer simulations and density functional theory indicate formation of more highly ordered smectic phases. The range of experimental applicability h strongly widened by the extension of the viriai theory to wormlike chains by Khokhlov and Semenov (1981, 1982). Fmally, experimental results for a number of carefully studied, charged and uncharged colloids and polymers are summarized and wmpared to theoretical results. IE many cases the agreement is semi-quantitative.

689 citations


Journal ArticleDOI
TL;DR: A review of the primate literature indicates that displacement activities tend to occur in situations of psychosocial stress and that their frequency of occurrence is affected by anxiogenic and anxiolytic drugs as mentioned in this paper.

549 citations


Journal ArticleDOI
15 Jul 1992
TL;DR: This paper shows why the operations of scaling and differentiation cannot be separated and permits us to construct in a systematic way multiscale, cartesian differential invariants, i.e. true image descriptors that exhibit manifest invariance with respect to a change of cartesian coordinates.
Abstract: Why and how one should study a scale-space is prescribed by the universal physical law of scale invariance, expressed by the so-called Pi-theorem. The fact that any image is a physical observable with an inner and outer scale bound, necessarily gives rise to a ‘scale-space representation’, in which a given image is represented by a one-dimensional family of images representing that image on various levels of inner spatial scale. An early vision system is completely ignorant of the geometry of its input. Its primary task is to establish this geometry at any available scale. The absence of geometrical knowledge poses additional constraints on the construction of a scale-space, notably linearity, spatial shift invariance and isotropy, thereby defining a complete hierarchical family of scaled partial differential operators: the Gaussian kernel (the lowest order, resettling operator) and its linear partial derivatives. They enable local image analysis through the detection of local differential structure in a robust way, while at the same time capturing global features through the extra scale degree of freedom. In this paper we show why the operations of scaling and differentiation cannot be separated. This framework permits us to construct in a systematic way multiscale, cartesian differential invariants, i.e. true image descriptors that exhibit manifest invariance with respect to a change of cartesian coordinates. The scale-space operators closely resemble the receptive field profiles found in mammalian frontend visual systems.

456 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the mechanisms behind the formation and growth of silica particles prepared from tetraalkoxysilanes in alcoholic solutions of water and ammonia, and concluded that the growth proceeds through a surface reaction-limited condensation of hydrolyzed monomers or small oligomers.

450 citations


Journal ArticleDOI
21 Aug 1992-Science
TL;DR: The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotroPE, and thyrotrope cell types.
Abstract: A point mutation in the POU-specific portion of the human gene that encodes the tissuespecific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid-stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative α helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elments but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes.

439 citations


Journal ArticleDOI
02 Oct 1992-Science
TL;DR: An estimate of world-wide glacier sensitivity based on a modeling study of 12 selected glaciers situated in widely differing climatic regimes shows that for a uniform 1 K warming the area-weighted glacier mass balance will decrease by 0.40 meter per year.
Abstract: Recent field programs on glaciers have supplied information that makes simulation of glacier mass balance with meteorological models meaningful. An estimate of world-wide glacier sensitivity based on a modeling study of 12 selected glaciers situated in widely differing climatic regimes shows that for a uniform 1 K warming the area-weighted glacier mass balance will decrease by 0.40 meter per year. This corresponds to a sea-level rise of 0.58 millimeter per year, a value significantly less than earlier estimates.

398 citations


Journal ArticleDOI
TL;DR: Scavenging of superoxide anions, inhibition of myeloperoxidase release and activity as well as a possible interference with the assembly of active NADPH-oxid enzyme may account for the inhibition of inflammatory process by gallic acid.
Abstract: Gallic acid was found to possess anti-inflammatory activity towards zymosan-induced acute food pad swelling in mice. In vitro studies on the mode of action of gallic acid revealed that this compound interferes with the functioning of polymorphonuclear leukocytes (PMNs). Scavenging of superoxide anions, inhibition of myeloperoxidase release and activity as well as a possible interference with the assembly of active NADPH-oxidase may account for the inhibition of inflammatory process by gallic acid. Structure-activity relationship analysis showed that the o-dihydroxy group of gallic acid is important for the inhibitory activity in vitro

Journal ArticleDOI
18 Jun 1992-Nature
TL;DR: It is concluded that p21ras mediates insulin-and PDGF-induced activation of ERK2, and direct introduction of p21ra oncoprotein into cells in the absence of growth factors activates ERKs within five minutes, which indicates that normal p 21ras may be involved in the activation ofERKs by growth factors.
Abstract: MANY growth factors upon stimulation of their receptors induce the activity of extracellular signal-regulated kinases, ERKs, also known as MAP kinases1,2. Several of these growth factors also activate the ras proto-oncogene product, p21ras (Ras), by stimulating the conversion of the inactive GDP-bound form of Ras to the active GTP-bound form3–6. We have shown that direct introduction of p21ras oncoprotein into cells in the absence of growth factors activates ERKs within five minutes7, which indicates that normal p21ras may be involved in the activation of ERKs by growth factors. Here we use a recombinant vaccinia virus expressing an interfering mutant of p21ras, RasAsn17, to investigate this question. In NIH3T3 cells that overexpress the insulin receptor, this recombinant virus inhibits insulin-induced activation of ERK2 completely, but there is no inhibition of insulin-induced activation of phosphatidyl-inositol-3-kinase. In rat-1 cells the recombinant virus inhibited ERK2 activity induced by platelet-derived growth factor (PDGF) but not by phorbol ester. We conclude that p21ras mediates insulin-and PDGF-induced activation of ERK2.

Journal ArticleDOI
TL;DR: A case‐control study comparing 223 women aged 38 to 75 years presenting with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer, who participated in a population‐based breast cancer screening program.
Abstract: Life-style has a major influence on the incidence of breast cancer. To evaluate the effects of life-style related metabolic-endocrine factors on breast cancer risk we conducted a case-control study comparing 223 women aged 38 to 75 years presenting with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer, who participated in a population-based breast cancer screening program. Women reporting diabetes mellitus were excluded. Sera from 110 women of the same age group presenting with early stage melanoma, lymphoma or cervical cancer were used as a second ‘other-cancer control group’. Serum levels of C-peptide were significantly higher in early breast cancer cases compared to controls. The same was found for the ratios C-peptide to glucose or C-peptide to fructosamine, indicating insulin resistance. Sex hormone binding globulin was inversely, triglycerides and available estradiol were positively related to C-peptide. Serum C-peptide levels were related to body mass index (BMI), and to waist/hip ratio (WHR), in particular in controls. However, the relative increase of C-peptide, C-peptide to glucose or C-peptide to fructosamine in cases was independent of BMI or WHR. The log relative risk was linearly related to the log C-peptide levels. Relative risk according to quintiles, and adjusted for age, family history, BMI and WHR, for women at the 80% level was 2.9 as compared with those at the 20% level for C-peptide. Elevated C-peptide or C-peptide to fructosamine values were not observed in the sera from women belonging to the ‘other-cancer control group’. This study suggests that hyperinsulinemia with insulin resistance is a significant risk factor for breast cancer independent of general adiposity or body fat distribution. © 1992 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: Results suggest that PIP kinase activity may be under control of PA levels in membranes, which may have important implications for the regulation of cellular responses by agonist-induced phosphoinositide turnover.

Journal ArticleDOI
TL;DR: In this article, the authors used fuzzy classification to determine land suitability from multivariate point observations of soil attributes, topographically controlled site drainage conditions, and minimum contiguous areas, and compared the results obtained with conventional Boolean methods.
Abstract: SUMMARY Because conventional Boolean retrieval of soil survey data and logical models for assessing land suitability treat both spatial units and attribute value ranges as exactly specifiable quantities, they ignore the continuous nature of soil and landscape variation and uncertainties in measurement which can result in the misclassification of sites that just fail to match strictly defined requirements. This paper uses fuzzy classification to determine land suitability from (i) multivariate point observations of soil attributes, (ii) topographically controlled site drainage conditions, and (iii) minimum contiguous areas, and compares the results obtained with conventional Boolean methods. The methods are illustrated using data from the Alberta Agricultural Department experimental farm at Lacombe in Alberta, Canada. Data on site elevation and soil chemical and physical properties measured at 154 soil profiles were interpolated by ordinary block kriging to 15 m × 15 m cells on a 50 × 50 grid. The soil property data for each cell were classified by Boolean and fuzzy methods. The digital elevation model created by interpolating the elevation data was used to determine the surface drainage network and map it in terms of the numbers of cells draining through each cell on the grid. This map was reclassified to yield Boolean and fuzzy maps of surface wetness which were then intersected with the soil profile classes. The resulting classification maps were examined for contiguity to locate areas where a block of minimum size (45m × 45m) could be located successfully. In this study Boolean methods reject larger numbers of cells than fuzzy classification, and select cells that are insufficiently contiguous to meet the aims of the land classification. Fuzzy methods produce contiguous areas and reject less information at all stages of the analyses than Boolean methods. They are much better than Boolean methods for classification of continuous variation, such as the results of the drainage analysis.

Journal ArticleDOI
TL;DR: From these experiments it is clear that exposure time and power density determine the effects of laser irradiation: both stimulation and inhibition of the observed cell properties can be obtained with the same laser on the same cells.
Abstract: The absorption spectrum of human fibroblast monolayers showed several absorption peaks, among them one at a wave-length of 630 nm. Cultures of these fibroblasts were subjected to He-Ne laser (632.8 nm) irradiation of various energy doses by varying power density and exposure time. On three consecutive days the cell monolayers were irradiated for periods between 0.5 and 10 min. Laser power varied from 0.55 to 5.98 mW. Both cell number and collagen type I production were determined for each irradiation condition within one experiment. Results show that laser power below 2.91 mW could enhance cell proliferation (as determined by cell counting), whereas higher laser power (5.98 mW) had no effect. Stimulatory effects were most pronounced at irradiation times between 0.5 and 2 min. Collagen type I production (as determined by an ELISA) was affected in the opposite direction to cell proliferation: when the cell proliferation was increased, collagen type I production was decreased. From these experiments it is clear that exposure time and power density determine the effects of laser irradiation. Both stimulation and inhibition of the observed cell properties can be obtained with the same laser on the same cells.

Journal ArticleDOI
18 Sep 1992-Cell
TL;DR: This work identified lamin B1 as a MAR-binding protein, which provides evidence for a specific interaction of DNA with the nuclear lamina, and identified internal and peripheral binding sites that show specific and saturable binding of MARs from different organisms.

Journal ArticleDOI
TL;DR: The Dutch version of EPDS was found to be a self-rating scale with good psychometric characteristics which measures what it claims to measure: the strength of depressive symptoms.

Journal ArticleDOI
TL;DR: Human Tamm-Horsfall glycoprotein has been purified from the urine of one male by a combination of three liquid-chromatographic techniques, and the primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by 1H-NMR spectroscopy.
Abstract: Human Tamm-Horsfall glycoprotein has been purified from the urine of one male. The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q-Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. In total, more than 150 carbohydrate-containing fractions were obtained, some of which still contained mixtures of oligosaccharides. The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. The types of compounds identified range from non-fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text]

Journal ArticleDOI
Theo Wubbels1
TL;DR: In this article, the authors argue that one important reason for the poor transfer is that teacher education programs fail to influence student teachers' preconceptions, which can be adequately described as "world images".

Journal ArticleDOI
TL;DR: It is concluded that variation in the costs of synthesis of whole plant biomass cannot explain interspecific variation in relative growth rate of herbaceous species.
Abstract: The chemical composition of 24 plant species which showed a three-fold range in potential growth rate was investigated The carbon content of whole plants was lower for fast-growing species than for slow-growing ones Fast-growing species accumulated more organic N-compounds, organic acids and minerals, whereas slow-growing species accumulated more (hemi)cellulose, insoluble sugars and lignin No correlations with relative growth rate were found for soluble phenolics, soluble sugars and lipids The costs to construct 1 g of plant biomass were rather similar for fast- and slow-growing species, both when expressed as C needed for C-skeletons, as glucose to provide ATP and NAD(P)H, and as total glucose costs Therefore, we conclude that, despite the differences in chemical composition between fast- and slow-growing species, variation in the costs of synthesis of whole plant biomass cannot explain interspecific variation in relative growth rate of herbaceous species

Journal ArticleDOI
TL;DR: In light of contemporary variations in subcultural meanings and values, a postmodern view is suggested in which reflexive responsibility is focal.
Abstract: Psychological theories and practices frequently neglect the extent to which their subject matter is historically and culturally defined. This issue is explored in the context of theories and therapies related to bereavement. Contemporary orientations emphasize the importance of breaking bonds with the deceased and the return of survivors to autonomous lifestyles. Placing the orientation in cultural and historical context reveals that it is largely a product of a modernist worldview. Within the romanticist ethos of the preceding century, such breaking of bonds would destroy one's identity and the meaning of life. In light of contemporary variations in subcultural meanings and values, a postmodern view is suggested in which reflexive responsibility is focal.

Journal ArticleDOI
TL;DR: Nuclear matrices of mouse NIH 3T3-fibroblasts and rat liver cells, isolated by nuclease treatment and high salt extraction, are demonstrated to contain phosphatidylinositol 4-kinase (PdtIns 4-Kinase), phosphate 4-phosphate 5-kinases (PtdIns(4)P 5- Kinase), diacylglycerol kinase, and phospholipase C.

Journal ArticleDOI
TL;DR: There is a need for studies correlating clinical efficacy and tolerability of liposomal amphotericin B with the pharmacokinetic properties of these formulations.
Abstract: Amphotericin B remains a very important drug for the treatment of fungal infections despite its toxicity. Encapsulation of amphotericin B into liposomes appears to reduce the toxic effects and to improve the clinical efficacy, allowing higher dosages to be given. The exact mechanism behind the reduced toxicity is not yet known.

Journal ArticleDOI
TL;DR: The magnetic immuno PCR assay (MIPA), which combines immunomagnetic separation by using specific monoclonal antibodies and PCR, was used to directly detect salmonellae in feces from humans.
Abstract: Direct polymerase chain reaction (PCR)-based detection with fecal specimens is hampered by inhibitory compounds, such as bilirubin and bile salts. These fecal compounds showed significant inhibition of PCR at low concentrations (10 to 50 micrograms/ml). For direct PCR analysis, fecal samples must be diluted 500-fold to overcome inhibition. Therefore, the magnetic immuno PCR assay (MIPA), which combines immunomagnetic separation by using specific monoclonal antibodies and PCR, was used to directly detect salmonellae in feces from humans. Immunomagnetically extracted stool samples needed to be diluted only 10-fold when 1 microgram of T4 gene 32 protein was added to the PCR. The MIPA sensitivity obtained was 10(5) CFU/ml of feces. A panel of monoclonal antibodies specific for Salmonella serogroups A to E was used to extract salmonellae from clinical samples. MIPA detection of salmonellae occurred with 11 out of 14 stool samples stored at 4 degrees C for 2 months. MIPA detection of salmonellae in stool samples is a promising, fast method for detection and identification.

Journal ArticleDOI
TL;DR: It is shown that, like the POUHD, the Oct‐1 POUS domain can bind autonomously to DNA but with low affinity, and a model for the way in which an additional conserved domain adds further specificity to DNA recognition by homeodomain proteins is suggested.
Abstract: The POU domain is a conserved DNA binding region of approximately 160 amino acids present in a family of eukaryotic transcription factors that play regulatory roles in development. The POU domain consists of two subdomains, the POU-specific (POUS) domain and a POU-type homeodomain (POUHD). We show here that, like the POUHD, the Oct-1 POUS domain can bind autonomously to DNA but with low affinity. DNA binding studies and in vitro binding site selection revealed that the POU subdomains each have a different sequence specificity. The binding consensus of the POUS domain [gAATAT(G/T)CA] and POUHD (RTAATNA) respectively overlap the 'left half' and right half' of the POU domain recognition sequence [a(a/t)TATGC(A/T) AAT(t/a)t]. In addition to the core sequence, which is very similar to the octamer motif (ATGCAAAT), the flanking bases make a significant contribution to the binding affinity of the POU domain. Interestingly, at some positions the sequence preferences of the isolated POU subdomains are distinct from those of the POU domain, suggesting that the POU domain binding site is more than a simple juxtaposition of the POUS and POUHD target sequences. In addition, analysis of the binding kinetics of the POU domain and POUHD indicates that the POUS domain enhances the binding affinity by reducing the dissociation rate. Our results show that the POU domain proteins have DNA binding properties distinct from those of classic homeodomain proteins. We suggest a model for the way in which an additional conserved domain adds further specificity to DNA recognition by homeodomain proteins.

Journal ArticleDOI
TL;DR: Results indicate that disorders occurring in early life may underlie abnormal functional development in later life, whereas (catch up) growth is mainly determined during the second half of pregnancy.

Journal ArticleDOI
TL;DR: Rape (Brassica napus L.) plants are efficient users of rock phosphates, and the biosynthesis and excretion of organic acids were investigated, partly by comparing physiological reactions to P deficiency of rape with those of an inefficient user of rock phosphate from the same family, hedge mustard.
Abstract: summary Rape (Brassica napus L.) plants are efficient users of rock phosphates. This has been ascribed to the excretion of malic and citric acids from the roots during phosphorus deficiency, resulting in a decrease of the pH in the rhizosphere and a consequent solubilization of the rock phosphate. In this paper the biosynthesis and excretion of organic acids were investigated, partly by comparing physiological reactions to P deficiency of rape with those of an inefficient user of rock phosphate from the same family, hedge mustard (Sisymbrium officinale Scop.). In the leaves of both species, both citrate levels and phosphoenolypyruvate carboxylase were nearly doubled in P–deficient plants, and the citrate/sugar ratio in the phloem exudate into EDTA solution was doubled as well. After exposure of the shoots of rape plants to 14CO2 in the light, the specific activities of citrate in the root and in the nutrient solution were ten times higher than those of malate, and also much higher than the respective activities of citrate in P–sufficient controls. It is suggested that citrate produced in the leaf is exported to the roots, where it is accumulated in the excretion region. Malic acid which is prevailing in the exudate is probably newly–synthesized within the excreting root segment. When no phosphate is supplied, this excretion zone is located 1–2 cm behind the root tips. However, when rock phosphate is applied locally this zone shifts along the root to that part which is in direct contact with the rock phosphate particles. No accumulation and excretion of organic acids could be observed with the roots of P–deficient Sisymbrium.

Journal ArticleDOI
TL;DR: It is demonstrated that the purified EGFR can be cosedimented with purified filamentous actin (F-actin) indicating a direct association between EGFR and actin.
Abstract: In a number of recent studies it has been shown that in vivo part of the EGF receptor (EGFR) population is associated to the actin filament system. In this paper we demonstrate that the purified EGFR can be cosedimented with purified filamentous actin (F-actin) indicating a direct association between EGFR and actin. A truncated EGFR, previously shown not to be associated to the cytoskeleton, was used as a control and this receptor did not cosediment with actin filaments. Determination of the actin-binding domain of the EGFR was done by measuring competition of either a polyclonal antibody or synthetic peptides on EGFR cosedimentation with F-actin. A synthetic peptide was made homologous to amino acid residues 984-996 (HL-33) of the EGFR which shows high homology with the actin-binding domain of Acanthamoeba profilin. A polyclonal antibody raised against HL-33 was found to prevent cosedimentation of EGFR with F-actin. This peptide HL-33 was shown to bind directly to actin in contrast with a synthetic peptide homologous to residues 1001-1013 (HL-34). During cosedimentation, HL-33 competed for actin binding of the EGFR and HL-34 did not, indicating that the EGFR contains one actin-binding site. These results demonstrate that the EGFR is an actin-binding protein which binds to actin via a domain containing amino acids residues 984-996.

Journal ArticleDOI
TL;DR: For suicidal adolescents, the suicide attempt seems embedded not just in the problems every adolescent has to deal with but in greater turmoil in their families, rooted in childhood and not stabilizing during adolescence, in combination with traumatic events during adolescence and social instability in the year preceding the attempt.
Abstract: OBJECTIVE: Although the relationship between experience of problematic life events and adolescent suicidal behavior has frequently been recognized during the past decade, few studies of life events have been initiated that discriminated between adolescent suicide attempters and depressed adolescents. Therefore, the authors compared adolescent suicide attempters with both depressed and nondepressed adolescents who never attempted suicide with respect to life events that happened in two periods: childhood (defined as the period up to age 12 years) and adolescence (age 12 and older). METHOD: Using a semistructured interview, the authors gathered life event data about childhood and adolescence from three groups of adolescents: 48 suicide attempters, 66 depressed adolescents who had never made a suicide attempt, and 43 nondepressed adolescents who had never made a suicide attempt. RESULTS: The group of adolescents who attempted suicide differed from both of the other groups in that they had experienced more turmoil in their families, starting in childhood and not stabilizing during adolescence. During adolescence, they were more often sexually abused. During the last year before the attempt, further social instability, such as changes in residence and having to repeat a class, occurred. CONCLUSIONS: For suicidal adolescents, the suicide attempt seems embedded not just in the problems every adolescent has to deal with but in greater turmoil in their families, rooted in childhood and not stabilizing during adolescence, in combination with traumatic events during adolescence and social instability in the year preceding the attempt. Language: en