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)

The association between psychotic symptoms and violence is unclear, due in part to methodological features of investigations that have examined this question, and in part to the fact that the association likely differs by disorder and treatment conditions. Using data from The Comparative Study of the Prevention of Crime and Violence by Mentally Ill Persons, we examined 128 men with schizophrenia or schizoaffective disorder discharged from general and forensic psychiatric hospitals in Canada, Finland, Germany, and Sweden. The association between symptoms and aggressive behavior was studied during two 6 month periods when the patients lived in the community. Severe positive and negative symptoms of psychosis, depression, and anxiety were measured at the beginning of each of the 6 month periods. In addition, at the beginning of the second 6 month period changes in symptoms in the previous period were indexed. Aggressive behavior was measured in each 6 month period by reports from patients and from collaterals. During the first 6 months post-discharge, after controlling for the presence of antisocial personality disorder or PCL score and past diagnoses of alcohol/drug abuse/dependence, the presence of a severe positive symptom significantly increased the risk of aggressive behavior. During the second 6 month period, after controlling for antisocial personality disorder or PCL score and self-reported alcohol/drug use, the presence of a severe positive symptom, a TCO symptom, and an increase in TCO symptoms significantly increased the risk of aggressive behavior. Neither depot medications nor obligatory community treatment reduced the risk of aggressive behavior after controlling for the presence of a severe positive symptom and/or TCO symptoms. These findings suggest that, among men with schizophrenia being treated in the community, the presence of severe psychotic symptoms and the development of TCO symptoms are antecedents of aggressive behavior.
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PMID:The antecedents of aggressive behavior among men with schizophrenia: a prospective investigation of patients in community treatment. 1289 6

Recent work using expression profiling to computationally predict the estrogen receptor (ER) status of breast tumors has revealed that certain tumors are characterized by a high prediction uncertainty ('low-confidence'). We analyzed these 'low-confidence' tumors and determined that their 'uncertain' prediction status arises as a result of widespread perturbations in multiple genes whose expression is important for ER subtype discrimination. Patients with 'low-confidence' ER+ tumors exhibited a significantly worse overall survival (P=0.03) and shorter time to distant metastasis (P=0.004) compared with their 'high-confidence' ER+ counterparts, indicating that the 'high-' and 'low-confidence' binary distinction is clinically meaningful. We then discovered that elevated expression of the ERBB2 receptor is significantly correlated with a breast tumor exhibiting a 'low-confidence' prediction, and this association was subsequently validated across multiple independently derived breast cancer expression datasets employing a variety of different array technologies and patient populations. Although ERBB2 signaling has been proposed to inhibit the transcriptional activity of ER, a large proportion of the perturbed genes in the 'low-confidence'/ERBB2+ samples are not known to be estrogen responsive, and a recently described bioinformatic algorithm (DEREF) was used to demonstrate the absence of potential estrogen-response elements (EREs) in their promoters. We propose that a significant portion of ERBB2's effects on ER+ breast tumors may involve ER-independent mechanisms of gene activation, which may contribute to the clinically aggressive behavior of the 'low-confidence' breast tumor subtype.
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PMID:Classifying the estrogen receptor status of breast cancers by expression profiles reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2 receptor. 1457 Jul 15

Despite the devastating impact that bipolar disorder has on the lives of millions worldwide, little is known for certain about its etiology or pathophysiology. Whereas research has traditionally focused on biogenic amines, it is becoming increasingly more apparent that intracellular pathways are involved in the etiology and treatment of the disease and that a true understanding of the pathophysiology of bipolar disorder must address its neurobiology at different physiological levels, that is, molecular, cellular, systems and behavioral levels. There is now considerable biochemical evidence that the antimanic agents lithium and valproate robustly activate the ERK signaling cascade in therapeutically relevant paradigms. This raises the possibility that this pathway may play a role in the antimanic effects of these agents. The present paper reviews behavioral studies that may shed light on the involvement of the ERK pathway in affective-like behaviors in animals. The available literature suggests that genetic manipulations of the brain-derived neurotrophic factor (BDNF)-ERK kinase pathway produces a variety of changes in affective-like behaviors, with most changes consistent with manic-like behavior. Thus, overall, mice with targeted mutation of the BDNF gene exhibited increased spontaneous locomotion and increased response to acute amphetamine, altered response to chronic cocaine, increased aggression, increase in risk-taking behavior, as demonstrated by time spent in the center of an open field, and changes in eating patterns. Although it has to be acknowledged that the currently available behavioral data from the BDNF-ERK pathway mutants is less than ideal to offer real substantiation relating this pathway to bipolar disorder, the data still supports the possibility that this pathway modulates manic-like behavior in animals, and perhaps mania in humans.
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PMID:Possible involvement of the ERK signaling cascade in bipolar disorder: behavioral leads from the study of mutant mice. 1466 41

To describe lifetime mental disorders among perpetrators of severe inter-personal crimes and to identify the problem domains most closely associated with aggression and a history of repeated violent criminality, we used structured interviews, clinical assessments, analyses of intellectual functioning, medical and social files, and collateral interviews in 100 consecutive subjects of pretrial forensic psychiatric investigations. Childhood-onset neuropsychiatric disorders [attention-deficit/hyperactivity disorder (AD/HD), learning disability, tics and autism spectrum disorders] affected 55% of the subjects and formed complex comorbidity patterns with adult personality disorders [including psychopathic traits according to the Psychopathy Checklist (PCL-R)], mood disorders and substance abuse. The closest psychiatric covariates to high Lifetime History of Aggression (LHA) scores and violent recidivism were the PCL-R scores and childhood conduct disorder (CD). Behavioral and affective PCL-R factors were closely associated with childhood AD/HD, CD, and autistic traits. The results support the notion that childhood-onset social and behavioral problems form the most relevant psychiatric symptom cluster in relation to pervasive adult violent behavior, while late-onset mental disorders are more often associated with single acts of violent or sexual aggression.
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PMID:Adult psychopathic personality with childhood-onset hyperactivity and conduct disorder: a central problem constellation in forensic psychiatry. 1467 46

Oncogenes, the abnormal forms of proto-oncogenes, were shown to be involved in malignant transformation and in tumor progression. c-erbB2/HER2/neu is member of EGFR family and encodes the p185 protein, which functions as a tyrosine-kinase. Gene amplification and/or p185 overexpression were reported to be associated with poor prognostic in cancer. Our purpose was to investigate p185 immunohistochemical expression in breast carcinomas and in the corresponding axillary lymph nodes metastases and to identify possible correlation between p185 and other factors of poor prognostic, such as loss of hormonal receptors expression. In our study, 40.91% of cases were erbB-2 positive, p185 expression being maintained from the primary tumors to axillary metastases and associated with positive nodal status and with the absence of hormonal receptors expression (p < 0.05). These findings support the hypothesis the c-erbB2 is an advantageous acquisition for the aggressive behavior of the tumor cell and for its ability to invade and metastasize.
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PMID:[Overexpression of c-erbB-2 gene product is associated with poor prognosis factors in breast carcinoma]. 1475 39

Although a large body of research has established the relevance of psychopathy to adult offenders, its relevance to adolescent offenders is far less clear. The current study evaluated the clinical, psychosocial and criminal correlates of psychopathic traits in a sample of 226 male and female incarcerated adolescent offenders. According to an 18-item version of the Psychopathy Checklist-Youth Version (PCL-YV; Forth, Kosson, & Hare, 2003), only 9.4% exhibited a high level of psychopathic traits (PCL-YV>/=25). Consistent with past research, higher PCL-YV scores were positively associated with self-reported delinquency and aggressive behavior and were unrelated to emotional difficulties. Although higher PCL-YV scores were associated with the experience of physical abuse, the only psychosocial factor to predict PCL-YV scores was a history of non-parental living arrangements (e.g. foster care). In terms of criminality, a violent/versatile criminal history was positively associated with psychopathic traits. However, PCL-YV scores were unrelated to participants' official criminal records for total, non-violent, violent, and technical violation convictions. In conclusion, the data partially support the construct validity of psychopathy with adolescent offenders, but some inconsistencies with prior adult and adolescent psychopathy research were evident. These issues are discussed.
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PMID:Psychopathic traits in adolescent offenders: an evaluation of criminal history, clinical, and psychosocial correlates. 1496 79

Few studies have compared self-report and clinician-administered measures of youth psychopathic features in juvenile-justice settings in terms of antisocial behavior and treatment indices. In a sample of 85 adjudicated delinquents, the predictive validities of the Antisocial Process Screening Device (APSD), the modified Childhood Psychopathy Scale (mCPS), and the Hare Psychopathy Checklist: Youth Version (PCL:YV) were tested. Three indices of institutional antisocial behavior (physical aggression; verbal aggression; administrative infractions) and two indices of treatment progress (time to treatment level promotion; whether treatment levels were dropped) were used as external correlates. The self-report measures (mCPS more so than APSD) were more consistently and strongly related to antisocial behavior and to the days required to progress in treatment than the PCL:YV. The following issues are discussed: (i) implications of the potential impact of measurement format on the understanding and predictive validity of youth psychopathy features and measures; (ii) the differential predictive validity of self-report versus clinician-administered measures; and (iii) the potential practical utility of measures of psychopathic features in youth.
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PMID:The relationship between psychopathic features, violence and treatment outcome: the comparison of three youth measures of psychopathic features. 1496 82

The Psychopathy Checklist-Revised (PCL-R) has been conceptualized as indexing two distinct but correlated factors. Previous research has established that these factors demonstrate distinct patterns of relations with external criteria. However, more recent findings suggest that the PCL-R psychopathy construct may encompass three distinguishable factors, reflecting affective, interpersonal, and behavioral symptoms. Here, we evaluated the validity of this newer three-factor model of the PCL-R factors with reference to external criteria from the domains of personality, antisocial behavior; and adaptive functioning in a sample of 310 incarcerated offenders. The interpersonal factor was related to social dominance, low stress reactivity, and higher adaptive functioning; the affective factor was correlated with low social closeness and violent offending; and the behavioral factor was associated with negative emotionality, disinhibition, reactive aggression, and poor adaptive functioning. These findings provide support for the convergent and discriminant validity of these psychopathy facets.
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PMID:Criterion-related validity of the three-factor model of psychopathy: personality, behavior, and adaptive functioning. 1499 49

One hundred forty-nine inpatients within a maximum security psychiatric facility were assessed with the Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995). Within the total sample, 68% had a psychotic disorder and 30% met criteria for psychopathy. Using confirmatory factor analysis, the authors tested the 2-factor PCL:SV model of psychopathy and recent 3- and 4-factor models. Results indicated good fit for each model, with the 4-factor model showing best overall fit. Structural equation modeling was used to determine which psychopathy factors predicted 6-month follow-up of inpatient aggression. The 2-, 3-, and 4-factor models, respectively, accounted for 16%.27%. and 3l% of the variance in aggression.
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PMID:Confirmatory factor analysis of the psychopathy checklist: screening version in offenders with axis I disorders. 1502 97

We report 62 cases of invasive micropapillary carcinoma of the breast characterized by delicate pseudopapillary structures lacking a fibrovascular core and by tubuloalveolar structures freely floating in clear, empty spaces. All patients but 1 were women (median age, 57 years; range, 25-89 years). Tumor size ranged from 0.7 to 10 cm (median, 2.8 cm); 54 (87%) were grade 3. Psammoma bodies were identified in 29 (47%). Focal to massive lymphatic permeation was present in 39 (63%). Architectural features were retained in the node metastases, dermal lymphatics, and recurrences. Fifty-six patients (90%) had metastatic axillary nodes: 18 tumors were estrogen receptor-positive (32%); 11 were progesterone receptor-positive (20%); HER2/neu was overexpressed in 53 (95%) and p53 in 39 (70%). A peculiar immunoreactivity for MUC1 limited to the cytoplasmic membrane oriented toward the stroma and an absence of immunoreactivity for E-cadherin in the same side of the cytoplasmic membrane indicated inversion of cell polarization and a disturbance in the cell adhesion molecules. Of 41 patients with available follow-up, 29 (71%) had local recurrence (mean, 30 months) and 20 (49%) died of disease. These results underscore the aggressive behavior and poor prognosis of this breast carcinoma variant. Aggressive preoperative neoadjuvant chemotherapy should be considered.
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PMID:Invasive micropapillary carcinoma of the breast: clinicopathologic study of 62 cases of a poorly recognized variant with highly aggressive behavior. 1519 58


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