RESUMEN
BACKGROUND: Cutbacks in clinical beds in regular and forensic psychiatry increase the burden on outpatient forensic care in The Netherlands.
AIM: Since 2007, Dutch forensic (flexible) assertive community treatment (For(F)ACT) teams offer outpatient, intensive treatment to forensic clients with complex mental health issues. As the need for this form of intensive treatment increases, so does the need for unambiguous indication criteria to facilitate adequate care and accompanied reduction in criminal behavior.
METHOD: The present study investigated the correlation between the clinical indication criteria and risk factors for criminal behavior in 76 For(F)ACT-clients, reviewing which criteria best predicted recidivism.
RESULTS: A weak correlation was found between the indication criteria and risk factors. Further receiver operating characteristic (ROC) analysis showed that a combination of clinical indication criteria best predicted recidivism.
CONCLUSION: The influential risk factors for For(F)ACT-clients are different compared to those for other groups of delinquents. Important treatment factors are breaking patterns, increasing safety and offering social and financial support. The clinical indication criteria should not be replaced by the START risk factors.
Asunto(s)
Servicios Comunitarios de Salud Mental/métodos , Psiquiatría Forense , Trastornos Mentales/terapia , Reincidencia/prevención & control , Atención Ambulatoria , Femenino , Humanos , Masculino , Países Bajos , Reincidencia/psicología , Medición de Riesgo , Factores de RiesgoRESUMEN
Anti-CV2 autoantibodies have recently been discovered in patients with paraneoplastic neurological diseases (PND). These disorders are associated with neuronal degeneration, mediated by autoimmune processes, in patients with systemic cancer. Anti-CV2 autoantibodies recognize a brain protein of 66 kDa developmentally regulated and specifically expressed by a subpopulation of oligodendrocytes in the adult brain. Here, we demonstrate that anti-CV2 sera recognize several post-translationally modified forms of Ulip4/CRMP3, a member of a protein family related to the axonal guidance and homologous to the Unc-33 gene product in Caenorhabditis elegans. The sequence of the human Ulip4/CRMP3 was determined and the gene localized to chromosome 10q25.2-q26, a region mutated in glioblastomas and containing tumour suppressor genes. The identification of the Ulip/CRMP proteins as recognized by anti-CV2 sera should provide new insights into the role of Ulip/CRMPs in oligodendrocytes and into pathophysiology of PND.
Asunto(s)
Autoanticuerpos/metabolismo , Proteínas Musculares , Proteínas del Tejido Nervioso/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/inmunología , Fosfoproteínas/inmunología , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos/inmunología , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Humanos Par 10/genética , ADN Complementario/genética , Epítopos/genética , Epítopos/inmunología , Células HeLa , Humanos , Immunoblotting , Hibridación in Situ , Ratones , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/genética , Procesamiento Proteico-Postraduccional/inmunología , Homología de Secuencia de Aminoácido , TransfecciónRESUMEN
The Epstein-Barr virus BMLF1 gene product EB2 has been shown to efficiently transform immortalized Rat1 and NIH 3T3 cells, to bind RNA, and to shuttle from the nucleus to the cytoplasm. In transient-expression assays EB2 seems to affect mRNA nuclear export of intronless RNAs and pre-mRNA 3' processing, but no direct proof of EB2 being involved in RNA processing and transport has been provided, and no specific functional domain of EB2 has been mapped. Here we significantly extend these findings and directly demonstrate that (i) EB2 inhibits the cytoplasmic accumulation of mRNAs, but only if they are generated from precursors containing weak (cryptic) 5' splice sites, (ii) EB2 has no effect on the cytoplasmic accumulation of mRNA generated from precursors containing constitutive splice sites, and (iii) EB2 has no effect on the 3' processing of precursor RNAs containing canonical and noncanonical cleavage-polyadenylation signals. We also show that in the presence of EB2, intron-containing and intronless RNAs accumulate in the cytoplasm. EB2 contains an Arg-X-Pro tripeptide repeated eight times, similar to that described as an RNA-binding domain in the herpes simplex virus type 1 protein US11. As glutathione S-transferase fusion proteins, both EB2 and the Arg-X-Pro repeat bound RNA in vitro. However, by using EB2 deletion mutants, we demonstrated that the effect of EB2 on splicing and RNA transport requires the C-terminal half of the protein but not the Arg-X-Pro repeat.
Asunto(s)
Arginina , Herpesvirus Humano 4/metabolismo , Proteínas Inmediatas-Precoces/metabolismo , Prolina , Empalme del ARN , Secuencias Repetitivas de Aminoácido , Transactivadores , Factores de Transcripción/metabolismo , Empalme Alternativo , Sitios de Unión , Transporte Biológico , Citoplasma , Regulación de la Expresión Génica , Células HeLa , Humanos , Proteínas ViralesRESUMEN
Point mutations in the p53 tumor suppressor gene are the most common genetic alterations in human cancers. The nature and location of these mutations can be informative in assessing the importance of putative carcinogenic agents. Potential associations between a given carcinogen and a specific mutation pattern can be substantiated when the exposure history of the patients is known. While the past exposure to environmental risk factors is often difficult to determine, documented occupational exposure to carcinogens presents a unique situation for evaluating this approach. Analysis usually involves working with paraffin-embedded tissues, fixed under conditions suboptimal for genetic analysis and stored for many years, since frozen tissues are not available in sufficient numbers. The particular methodological problems encountered with fixed samples are discussed here, using as illustration an ongoing study of oncogene and tumor suppressor gene mutations in archived bladder tumors of workers exposed to aromatic amines and nonexposed patients.
Asunto(s)
Carcinógenos/toxicidad , Análisis Mutacional de ADN , Genes p53/genética , Exposición Profesional/efectos adversos , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/genética , Secuencia de Bases , ADN de Neoplasias/análisis , Humanos , Datos de Secuencia Molecular , Mutación , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/epidemiologíaRESUMEN
Mutations in the p53 tumor suppressor gene are commonly found in the major human cancers and the mutational spectrum in some cancer types is consistent with the genotoxic effects of the associated environmental risk factors. Thus far there is little information on p53 mutations in cancers of factory workers with a history of carcinogen exposure in the workplace. Occupational exposure to vinyl chloride causes liver angiosarcomas (ASL) and also increases the risk of several other cancers. Loss of p53 function in osteo- and fibrosarcomas can occur by two different mechanisms, p53 mutation and amplification of the MDM2 gene. We examined tumors from five vinyl chloride-exposed patients, four with ASL and one with hepatocellular carcinoma (HCC), for evidence of MDM2 proto-oncogene amplification or p53 mutation in exons 5-8. Amplification of MDM2 was not found, but in two of the angiosarcomas an A:T to T:A missense mutation was detected. p53 sequence analysis of vinyl chloride associated cancers may provide valuable information on the relationship between carcinogen exposure and DNA damage in cancer-related genes.
Asunto(s)
ADN/efectos de los fármacos , ADN/genética , Genes p53/efectos de los fármacos , Genes p53/genética , Hemangiosarcoma/inducido químicamente , Hemangiosarcoma/genética , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Mutación/efectos de los fármacos , Proteínas Nucleares , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/genética , Proteínas Proto-Oncogénicas , Cloruro de Vinilo/efectos adversos , Adenina/fisiología , Anciano , Composición de Base , Secuencia de Bases , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Exones/genética , Amplificación de Genes/efectos de los fármacos , Amplificación de Genes/genética , Humanos , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Reacción en Cadena de la Polimerasa , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-mdm2 , Timidina/genéticaRESUMEN
Fertile life of oocytes is usually considered to be related to ovulation time. In the present study, fertile life of rat oocytes was studied in relation to resumption of meiosis. In pro-oestrus, meiotic resumption without concomitant ovulation was induced in most graafian follicles by injection of a small amount of LH or FSH followed by Nembutal. These follicles either ovulated or developed into luteinized unruptured follicles if Ovalyse (a GnRH analogue) was given 8 h after LH or FSH. In subsequent experiments, rats were injected with FSH or saline, and Nembutal; 4 or 8 h later, Ovalyse was given to induce ovulation; the rats were mated 14 h after Ovalyse. At day 20 of pregnancy, fetal survival was 30% in rats with meiosis advanced by 8 h, against 91% and 70% in rats advanced by 0 or 4 h, respectively. Mortality occurred mainly during pre-implantation and early post-implantation. Advanced resumption of meiosis may cause pre-ovulatory ageing of oocytes; consequently, viability of these oocytes after ovulation is reduced.
Asunto(s)
Meiosis/fisiología , Oocitos/fisiología , Folículo Ovárico/fisiología , Animales , Senescencia Celular/fisiología , Femenino , Muerte Fetal , Hormona Folículo Estimulante/farmacología , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Luteinizante/farmacología , Masculino , Meiosis/efectos de los fármacos , Oocitos/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Inducción de la Ovulación , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Preinvasive lesions of squamous cell carcinoma are well defined morphologically and provide a model for multistage carcinogenesis. Since alterations in the p53 tumor suppressor gene occur frequently in invasive esophageal squamous cell carcinoma, we examined a set of preinvasive lesions to investigate the timing of p53 mutation. Surgically resected tissues from nine patients with esophageal squamous cell carcinoma contained precursor lesions which had not yet invaded normal tissues. Immunohistochemistry showed high levels of p53 protein in both preinvasive lesions and invasive carcinomas in six cases; sequence analysis of all invasive tumors identified p53 missense mutations in two cases. Preinvasive lesions from both tumors with mutations plus one wild-type tumor were microdissected and sequenced. In one patient there were different mutations in the invasive carcinoma (codon 282, CGGarg > TGGtrp) and a preinvasive lesion (codon 272, GTGval > T/GTGleu/val). In a second case, an invasive carcinoma had a mutation in codon 175 (CGCarg > CAChis), and adjacent preinvasive lesions contained a wild-type sequence. A carcinoma and preinvasive lesion from the third case contained high levels of protein and a wild-type DNA sequence. Therefore, p53 mutation may precede invasion in esophageal carcinogenesis, and multifocal esophageal neoplasms may arise from independent clones of transformed cells. The timing of p53 protein accumulation is favorable for an intermediate biomarker in multistage esophageal carcinogenesis.