Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RON is a tyrosine kinase receptor that triggers scattering of normal cells and invasive growth of cancer cells on ligand binding. We identified a short RON mRNA, which is expressed in human lung, ovary, tissues of the gastrointestinal tract, and also in several human cancers, including ovarian carcinomas and cell lines from pancreatic carcinomas and leukemias. This transcript encodes a truncated protein (short-form RON; sf-RON), lacking most of the RON receptor extracellular domain but retaining the whole transmembrane and intracellular domains. Sf-RON shows strong intrinsic tyrosine kinase activity and is constitutively phosphorylated. Epithelial cells transduced with sf-RON display an aggressive phenotype; they shift to a nonepithelial morphology, are unable to form aggregates, grow faster in monolayer cultures, show anchorage-independent growth, and become motile. We show that in these cells, E-cadherin expression is lost through a dominant transcriptional repression pathway likely mediated by the transcriptional factor SLUG. Altogether, these data show that expression of a naturally occurring, constitutively active truncated RON kinase results in loss of epithelial phenotype and aggressive behavior and, thus, it might contribute to tumor progression.
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PMID:Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression. 1528 19

The authors used model-based cluster analysis to identify subtypes of criminal psychopaths on the basis of differences in personality structure. Participants included 96 male prisoners diagnosed as psychopathic, using the Psychopathy Checklist Revised (PCL-R; R. D. Hare, 1991). Personality was assessed using the brief form of the Multidimensional Personality Questionnaire (MPQ-BF; C. J. Patrick, J. J. Curtin, and A. Tellegen, 2002). The best-fitting model yielded two clusters. Emotionally stable psychopaths were characterized by low Stress Reaction and high Agency. Aggressive psychopaths were characterized by high Negative Emotionality, low Constraint, and low Communion. These results suggest that psychopaths as defined by the PCL-R includes distinct subtypes, distinguishable in terms of personality structure, that may reflect different etiologies.
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PMID:Identifying psychopathy subtypes on the basis of personality structure. 1205 77

Cholecystokinin (CCK) is the most abundant neuropeptide in the mammalian brain, and has been implicated in the regulation of a diversity of emotions and motivations including negative affect and stress responses. In this experiment, we assayed levels of CCK (CCK4/5 and CCK8) from tissue homogenates in intruder animals 6 h after resident-intruder inter-male aggression. Intruder animals that demonstrated submissive behavior (freezing and 22-kHz ultrasonic vocalizations) had higher levels of CCK in the tegmentum and posterior cortex as compared to non-submissive (i.e., "Friendly") intruder animals. Ultrasonic vocalizations (22-kHz) were positively correlated with CCK levels in the tegmentum, posterior cortex and pituitary. These data suggest that CCK may play a role in the generation of negative affective states indexed by 22-kHz ultrasonic calls in certain regions of the brain.
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PMID:Regional brain cholecystokinin changes as a function of friendly and aggressive social interactions in rats. 1546 47

Violence risk assessment constitutes a major concern in forensic psychiatry, psychology and related fields. Numerous instruments like the Hare Psychopathy Checklist (PCL-R, Hare, 1991) and the Violence Risk Appraisal Guide (VRAG) have been developed in the aim of improving precision in the prediction of violence. This study assesses the reliability index of the HCR-20 Violence Risk Assessment Scheme and evaluates its relationship with the PCL-R the Buss and Perry's self-report Aggression Questionnaire (AQ) and the type of offenses officially registered. All participants (n=86) are male adult offenders detained in a Belgian high-security forensic hospital. The mean IQ and age were respectively, 81,03 and 36,71. Items common to these instruments were omitted in order to avoid a circular effect. Results showed that the HCR-20 was significantly related to the PCL-R: the historical factor was strongly correlated to the PCL-R factor 2 while the clinical factor was strongly correlated to the PCL-R factor 1. The HCR-20 was significantly related to the AQ: the historical factor was strongly correlated to the AQ Physical Aggression factor and to the Anger factor. As regards to the HCR-20 relations with offenses, its Historical factor was related to both violent (assault and battery, robbery) and non-violent offenses (drug offenses, theft). Finally, the HCR-20 was also positively related to "instrumental" and rather premeditated homicide but negatively related to psychotic homicide. The overall findings are congruent with -published data on the convergent validity of the HCR-20.
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PMID:[Evaluation of the HCR-20 Violence Risk Assessment Scheme in a Belgian forensic population]. 1562 49

Childhood conduct disorder (CD) and adult psychopathic traits according to the Psychopathy Checklist Revised (PCL-R) were the closest psychiatric covariates to repeated violent crimes and aggression among offenders under forensic psychiatric investigation in Sweden. As psychopathy is not included in the present psychiatric diagnostic systems, we compared total and factor PCL-R scores to Axis I disorders, including childhood-onset neuropsychiatric disorders, and to Axis II personality disorders, to establish the convergence of psychopathic traits with other psychiatric diagnoses, and to identify possible unique features. Psychopathic traits were positively correlated with bipolar mood disorder and negatively with unipolar depression. The total PCL-R scores as well as the Factor 2 (unemotionality) and Factor 3 (behavioral dyscontrol) scores were significantly correlated with attention-deficit/hyperactivity disorder, Asperger's syndrome/high-functioning autistic traits, CD, substance abuse, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Cluster B personality disorders. The interpersonal Factor 1 showed none of these correlations and may capture features that are specific to psychopathy, distinguishing core psychopathy from other diagnostic definitions.
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PMID:The childhood-onset neuropsychiatric background to adulthood psychopathic traits and personality disorders. 1572 27

Gastrointestinal stromal tumors (GISTs) are rarely reported in the esophagus. The authors report a patient with an esophageal GIST, incidentally found after an echocardiogram. CT scan and endoscopic ultrasonography showed the tumor in the dependence of the muscularis propria of the esophageal wall. An Ivor-Lewis esophagectomy was performed. The tumor was well-circumscribed involving the submucosal and the muscular layers of the esophagus, measuring 13.5 x 8.5 x 7.6 cm, without involving the surgical margins. Histologically, the tumor consisted of spindle cells, with low mitotic index (2/50 HPF), that were immunoreactive for KIT (CD117) and CD34, consistent with GIST of high risk of aggressive behavior. No adjuvant therapy was given to the patient, who is alive and without evidence of disease 1 year after surgery. Since esophageal GISTs are rarely reported in the literature and usually have a poor prognosis, the diagnostic differentiation of these tumors from other more common mesenchymal neoplasms is essential, both for therapeutic and prognostic reasons.
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PMID:Esophageal GIST: therapeutic implications of an uncommon presentation of a rare tumor. 1577 48

This study evaluated the structural reliability, construct-related validity, and cultural validity generalization of the Hare Psychopathy Checklist: Screening Version (PCL:SV) in a sample of more than 560 male and female Swedish forensic psychiatric treatment patients, forensic evaluation patients, and criminal offenders. Structural reliability was excellent for most indices. PCL:SV scores were higher for males than females for total and Part 1 scores (interpersonal/affective features) but not for Part 2 (behavioral features). With some exceptions, PCL:SV scores were meaningfully related to aggression to others, a measure of risk for violence, substance use problems, personality disorder (positive), and psychosis (negative). Correlations between PCL:SV and aggression were larger for females than males, although the difference was smaller when personality disorder was held constant. The structural reliability and pattern of validity coefficients were comparable in these Swedish samples to other non-North American samples. Implications for the cross-cultural manifestation and correlates of psychopathy are discussed.
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PMID:Reliability and Validity Evaluation of the Psychopathy Checklist: Screening Version (PCL:SV) in Swedish correctional and forensic psychiatric samples. 1591 17

The post-traumatic stress disorder (PTSD) represents an original and frequent pathological entity concerning people confronted with one or more significant traumatic events. We present here a comparative study concerning subjects who present a post-traumatic stress disorder received in an anxiety disorder unit (ADU) or in a victims support association (VSA). One hundred and twenty seven people have been included in the study, according to DSMIV for PTSD, during three years. Fifty-seven came from a victim support association, 54 came from an anxiety disorder unit and 16 were common to both structures. The PCL-S (PTSD Checklist Scale) was used to rate the intensity of the PTSD. Age, sex, marital statute, type of traumatism, comorbidity and previous traumatisms were compared. PCLS scores were equivalent in the two settings. More women, younger subjects and more aggression were received in the victim support association. In the anxiety disorder unit more psychiatric comorbidity and more frequent antecedents of traumatism were seen. In the whole sample, two thirds of the people lived alone. Our results show that a victim support association receives people suffering from a definite post-traumatic stress disorder as intense on the PCL-S as in an anxiety disorder unit. More work has to be done on support association in the community, as they are confronted with significant PTSD problems.
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PMID:[Post-traumatic stress disorder in an anxiety disorder unit and in a victims support association]. 1597 43

The objective of the study was to explore the possibility of common signs and symptoms of childhood-onset neuropsychiatric disorders and personality disorders, especially psychopathy, in a cohort of violent offenders. A structured neuropsychiatric status comprising features recorded in childhood-onset neuropsychiatric disorders and adult personality disorders was assessed in 89 perpetrators of severe crimes against other persons, analysed for factor structure, and compared to clinical diagnostics of neuropsychiatric disorders and independent assessments of psychopathy rated by the Psychopathy Checklist Revised (PCL-R). One or several childhood-onset neuropsychiatric disorders [autism, attention-deficit/hyperactivity disorder (AD/HD), tics and learning disability] affected the majority of adult offenders. A factor analysis yielded four higher-order problem constellations: Executive Dysfunction, Compulsivity, Social Interaction Problems and Superficiality. All four constellations were positively correlated with life histories of aggression, stressing the clinical importance of these problems in adult forensic psychiatry. Compulsivity and Social Interaction Problems were associated with autistic traits and tics, Executive Dysfunction with AD/HD, conduct disorder and psychopathic as well as autistic traits. Superficiality was a distinct aspect of AD/HD and psychopathic traits, especially the PCL-R factor reflecting interpersonal callousness. Neuropsychiatric disorders and personality disorders such as psychopathy share common symptoms. The various facets of psychopathy are associated with executive dysfunction and empathy deficits with superficial understanding of self, others and the rules of communication.
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PMID:Clinical neuropsychiatric symptoms in perpetrators of severe crimes against persons. 1619 25

Neuroblastoma is a common solid tumor of childhood that is derived from the neural crest. Expression of epidermal growth factor (EGF) receptors (EGFRs) has been associated with enhanced cell growth and aggressive behavior in other tumors. Here, we examined the expression profile of EGFRs in neuroblastoma cell lines and primary tumors. We found that all 13 neuroblastoma cell lines examined expressed EGFR1 (HER1), most at readily detectable levels. Low levels of other human EGFR family receptors were also detected in almost all cell lines. All primary tumors examined expressed readily detectable levels of HER1 and HER3 and lower levels of HER2 and HER4. EGF had a significant effect on the proliferation of neuroblastoma cell lines in vitro. EGF treatment (100 ng/mL) of the cell lines SY5Y and NLF significantly increased cell number (P < 0.01). EGF stimulated more cells to enter S and G2-M phase, as suggested by flow cytometry, indicating that EGF increases cell number by increasing proliferation, with no appreciable change in apoptosis. EGF exposure resulted in receptor autophosphorylation and activation of both the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways. Exposure to 0.5 micromol/L ZD1839, a HER1-specific inhibitor, caused a 40% to 50% reduction in the number of SY5Y and NLF cells grown in medium containing 10% fetal bovine serum (P < 0.01). Even at 0.01 micromol/L, ZD1839 inhibited autophosphorylation of HER1 by EGF. At 0.1 micromol/L, it also blocked phosphorylation of AKT, but not MAPK, in NLF cells. Additional studies showed that the PI3K/AKT-specific inhibitor LY294002 had a more profound effect than the MAPK-specific inhibitor U0126 in blocking EGF-induced cell proliferation. This suggests that the PI3K/AKT pathway is the main signaling pathway responsible for the proliferation effects of EGF in neuroblastomas. Our results also indicate that ZD1839 is a potent inhibitor of neuroblastoma cell proliferation; therefore, it may be a useful, biologically based therapeutic agent for these tumors.
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PMID:Proliferation of human neuroblastomas mediated by the epidermal growth factor receptor. 1626 10


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