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Although previous studies have focused on the associations between peer group relations and cyber-aggression, limited attention has been paid to the heterogeneity in the functions of cyber-aggression. This study explored the unique associations of peer relations with proactive and reactive cyber-aggression and the possible mechanisms underlying them in a sample of adolescents using a longitudinal study design. A total of 829 middle school students completed the Cyber-rage and Cyber-reward Aggression Subscales of the Cyber-Aggression Typology Questionnaire, the Peer Relations Scale, the Social Information Processing-Attributional Bias Questionnaire, and the Self-efficacy for Aggression Scale twice at a 6-month interval. Multiple mediation analyses and bootstrapping were conducted using the Mplus 8 software. The results indicated that satisfying peer relations were negatively correlated with reactive cyber-aggression and positively associated with proactive cyber-aggression. Moreover, hostile intent attribution and self-efficacy for aggression mediated the associations between peer relations and both functions of cyber-aggression, however, in different ways. Unsatisfying peer relations were associated with higher levels of hostile intent attribution and lower levels of self-efficacy for aggression and predicted increases in reactive cyber-aggression. In contrast, satisfying peer relations were associated with lower levels of hostile intent attribution and higher levels of self-efficacy for aggression and predicted increases in proactive cyber-aggression. The findings indicated that different functions of cyber-aggression might be related to different mediation mechanisms, which sheds light on the prevention of cyber-aggression in the future.
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Agresión , Relaciones Interpersonales , Adolescente , China , Hostilidad , Humanos , Estudios Longitudinales , Grupo ParitarioRESUMEN
The popularity of research topics in clinical psychology has always been changing over time. In this study, we use Latent Dirichlet Allocation (LDA), a well-established statistical modeling approach in machine learning, to extract hot research topics in published review articles in clinical psychology. In Study 1, we use LDA to extract existing topics between 1981 to 2018 from the review articles published on three premium journals in clinical psychology. Results provide stable information about all topics and their proportions. In Study 2, we use a dynamic variant of LDA to identify the development of hot topics from 2007 to 2018. Results show that meta-analysis, psychotherapy, professional development, and depression constantly stay as hot topics all over the 12 years. We also find that behavior intervention has a clear rising trend since 2007. Our results provide a comprehensive summary of the popularity of research topics in clinical psychology in the last couple of years, and the results here can help clinical researchers form a structured view of past research and plan future research directions.
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Psicología Clínica , Investigación Biomédica , Predicción , Humanos , Modelos EstadísticosRESUMEN
BACKGROUND: Although internet-based cognitive behaviour therapy (ICBT) is an effective treatment for social anxiety disorder (SAD), a substantial proportion of patients do not achieve clinically significant improvement. More research is needed to identify which factors predict treatment adherence and outcomes. AIMS: The aims of this study were to (1) identify demographic and clinical factors associated with treatment adherence and outcomes in ICBT for social anxiety in China, and (2) explore whether low-intensity therapist support results in improved treatment adherence or outcomes. METHOD: Participants were assigned to either therapist-guided (N = 183) or self-guided ICBT (N = 72). Level of social anxiety was measured at both pre- and post-treatment. Treatment adherence and outcomes were analysed using a two-step linear and logistic regression approach. Clinical and demographic characteristics were examined. RESULTS: No significant group differences were found for treatment adherence or outcomes between the therapist-guided and self-guided conditions. Participants diagnosed with SAD were significantly less likely to drop out (OR 0.531, p = .03) compared with subclinical participants with social anxiety symptoms. Older participants (B = 0.17, SE = 0.04, p = .008) and participants with a diagnosis of SAD (B = 0.16, SE = 0.44, p = .01) tended to complete more modules. Participants who completed more modules (B = 0.24, SE = 0.03, p = .01) and participants who identified as female (B = -0.20, SE = 0.18, p = .04) reported greater reductions in SAD symptoms. CONCLUSIONS: Understanding of factors related to adherence and outcome is necessary to prevent drop-out and optimize outcome.
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Ansiedad , Terapia Cognitivo-Conductual , Internet , Ansiedad/terapia , China , Femenino , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Social feedback in the virtual environment is a critical part of successful virtual reality exposure therapy (VRET), and identifying the influences of virtual social feedback on social anxiety patients is necessary. AIMS: The present study aimed to explore the influences of ambiguous and negative virtual social feedback on social anxiety patients and a health control group (HCG). METHOD: Twenty-six social anxiety patients and 26 healthy participants were recruited. All participants were exposed to a virtual public speaking scenario. The participants were required to make two 3-minute speeches while the virtual audiences gave them either ambiguous feedback or negative feedback. The subjective units of discomfort (SUD) and heart rate were collected during the process. RESULTS: The results showed that SAD individuals reported higher levels of subjective anxiety than those in the HCG, and the between-group differences were larger in the mild ambiguous condition than in the intense negative condition. CONCLUSIONS: This study indicates that social anxiety patients have an interpretation bias towards ambiguous virtual social feedback. Therefore, it is important for VR-based interventions to take into account not only the valence of the feedback but also the ambiguity aspect.
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Retroalimentación Formativa , Fobia Social/psicología , Fobia Social/terapia , Habla , Terapia de Exposición Mediante Realidad Virtual/métodos , Adulto , Ansiedad/psicología , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Adulto JovenRESUMEN
Background: Social anxiety disorder (SAD) is one of the most prevalent psychological disorders and generally co-occurs with elevated shame levels. Previous shame-specific interventions could significantly improve outcomes in social anxiety treatments. Recent review suggests that integrating a more direct shame intervention could potentially increase the effectiveness of cognitive behavioral therapy. Web-based cognitive behavioral therapy (WCBT) has proven efficacy, sustaining benefits for 6 months to 4 years. Previous evidence indicated that shame predicted the reduction of social anxiety and mediated between engagements in exposure and changes in social anxiety during WCBT. Objective: This study aimed to design a shame intervention component through a longitudinal study and conduct a randomized controlled trial to investigate the effectiveness of a shame intervention component in reducing social anxiety symptoms and shame experience in a clinical sample of people with SAD. Methods: The development of a shame intervention component was informed by cognitive behavioral principles and insights from longitudinal data that measured the Experience of Shame Scale (ESS), the Coping Styles Questionnaire, and the Social Interaction Anxiety Scale (SIAS) in 153 participants. The psychoeducation, cognitive construct, and exposure sections were tailored to focus more on shame-related problem-solving and self-blame. A total of 1220 participants were recruited to complete questionnaires, including the ESS, the SIAS, the Social Phobia Scale (SPS), and diagnostic interviews. Following a 2-round screening process, 201 participants with SAD were randomly assigned into a shame WCBT group, a normal WCBT group, and a waiting group. After the 8-week WCBT intervention, the participants were asked to complete posttest evaluations, including the ESS, SIAS and SPS. Results: Participants in the shame WCBT group experienced significant reductions in shame levels after the intervention (ESS: P<.001; ηp2=0.22), and the reduction was greater in the shame intervention group compared to normal WCBT (P<.001; mean deviation -12.50). Participants in both the shame WCBT and normal WCBT groups experienced significant reductions in social anxiety symptoms (SIAS: P<.001; ηp2=0.32; SPS: P<.001; ηp2=0.19) compared to the waiting group after intervention. Furthermore, in the experience of social interaction anxiety (SIAS), the shame WCBT group showed a higher reduction compared to the normal WCBT group (P<.001; mean deviation -9.58). Problem-solving (SE 0.049, 95% CI 0.025-0.217) and self-blame (SE 0.082, 95% CI 0.024-0.339) mediated the effect between ESS and SIAS. Conclusions: This is the first study to design and incorporate a shame intervention component in WCBT and to validate its efficacy via a randomized controlled trial. The shame WCBT group showed a significant reduction in both shame and social anxiety after treatment compared to the normal WCBT and waiting groups. Problem-solving and self-blame mediated the effect of shame on social anxiety. In conclusion, this study supports previous findings that a direct shame-specific intervention component could enhance the efficacy of WCBT.
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Terapia Cognitivo-Conductual , Intervención basada en la Internet , Fobia Social , Vergüenza , Humanos , Masculino , Terapia Cognitivo-Conductual/métodos , Femenino , Fobia Social/terapia , Fobia Social/psicología , Adulto , Estudios Longitudinales , Resultado del Tratamiento , Adulto Joven , Persona de Mediana Edad , InternetRESUMEN
Introduction: Parental stress among primary caregivers of children with autism spectrum disorder (ASD) is a significant concern. While previous research indicates that both family and child factors substantially influence parental stress, a few studies have comprehensively examined these factors from family, parent, and child perspectives. Moreover, the psychological mechanisms underlying parental stress remain underexplored. Method: This study obtained a valid sample of 478 primary caregivers of children diagnosed with ASD in China and employed mediation and moderated mediation analyses to investigate the relationships between family adaptability and cohesion (FAC), ASD severity, parental self-efficacy, and parental stress. Result: Results revealed that higher FAC was linked to reduced parental stress through increased parental self-efficacy. The indirect effect of parental self-efficacy was more substantial for caregivers of children with severe symptoms than those with mild symptoms. Discussion: These findings offer insights into how FAC influences parental stress and underscore the importance of parental self-efficacy as a coping resource for mitigating parental stress. This study provides valuable theoretical and practical implications for understanding and addressing parental stress, particularly in families raising children with ASD.
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Despite the growing evidence for the attentional bias toward emotional related stimuli in patients with social anxiety disorder (SAD), it remains unclear how the attentional bias manifests in normal individuals with SAD and/or depressive traits. To address this question, we recruited three groups of normal participants with different psychiatric traits-individuals with comorbid SAD and depression (SADd, N = 19), individuals with only SAD (SAD, N = 15), and healthy control individuals (HC, N = 19). In a dot-probe paradigm, participants view angry, disgusted, and sad face stimuli with durations ranging from very brief (i.e., 14ms) that renders stimuli completely intangible, to relatively long (i.e., 2000ms) that guarantees image visibility. We find significant early vigilance (i.e., on brief stimuli) and later avoidance (i.e., on long stimuli) toward angry faces in the SADd group. We also find vigilance toward angry and disgusted faces in the SAD group. To our best knowledge, this is the first study to unify both vigilance and avoidance within the same experimental paradigm, providing direct evidence for the "vigilance-avoidance" theory of comorbid SAD and depression. In sum, these results provide evidence for the potential behavioral differences induced by anxiety-depression comorbidity and a single trait in non-clinical populations, but the lack of a depression-only group cannot reveal the effects of high levels of depression on the results. The limitations are discussed.
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This study examined a mediation model about whether perceived peer support (PPS) mediates the link between school incivility and academic burnout. More importantly, we also investigated how future academic self-salience (FASS) as a trait moderates this mediated relationship. We collected data from a sample of 475 students by a two-wave survey. Results indicate that PPS mediated the relationships for school incivility with academic burnout. Moderated mediation analysis intended to further reveal that PPS mediated the relationship for only those students with high FASS while what the current findings found are the separate effects of the mediation of PPS on the relationship between school incivility and academic burnout and the moderation of FASS on the relationship between PPS and academic burnout. Therefore, the findings underscore the significance of influence from peer relationships when investigating the relationship between school incivility and academic burnout. Further evidences are needed to prove the mediated moderation role of FASS.
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Non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (SCT) from family members has been reported, but its effectiveness and safety are not fully known. In this study, we examined the outcomes of 83 children and adolescents with nonmalignant (n = 11) or malignant (n = 72) disorders who underwent SCT mismatched at 2 or 3 HLA loci, either from the mother (n = 56), a noninherited maternal antigen (NIMA)-mismatched sibling (n = 14), or the father/a noninherited paternal antigen (NIPA)-mismatched sibling (n = 13). Engraftment was satisfactory. Severe (grade III-IV) acute graft-versushost disease (GVHD) was noted only in malignant disease, with an incidence of 21 of 64 evaluable patients. GVHD prophylaxis with a combination of tacrolimus and methotrexate was significantly associated with a lower risk of severe acute GVHD, compared with other types of prophylaxis (P = .04). Nine of 11 patients with nonmalignant disease and 29 of 72 patients with malignant disease were alive at a median follow-up of 26 months (range, 4-57 months). Outcomes were not significantly different among the 3 donor groups (mother versus NIMA-mismatched sibling versus father/NIPA-mismatched sibling) for the malignancy disorders. Our results indicate that non-T-cell-depleted HLA-haploidentical SCT may be feasible, with appropriate GVHD prophylaxis, for young recipients who lack immediate access to a conventional stem cell source.
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Quimerismo , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Tacrolimus/uso terapéutico , Adolescente , Trasplante de Médula Ósea/métodos , Niño , Preescolar , Quimioterapia Combinada , Enfermedades Genéticas Congénitas/terapia , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Estimación de Kaplan-Meier , Trasplante de Células Madre de Sangre Periférica/métodos , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Resultado del TratamientoRESUMEN
We performed autologous CD34+ stem cell transplantation in 3 patients with juvenile rheumatoid arthritis (JRA) refractory to conventional treatment. All patients had systemic type JRA. In case 1 (a 3-year-old boy), purified CD34+ cells from bone marrow were transplanted after a preconditioning regimen consisting of cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG) (40 mg/kg). However, the disease flared soon after transplantation. In case 2 (a 13-year-old girl) and case 3 (a 21-year-old woman), a preconditioning regimen consisting of etoposide (VP16) (2 g/m2), thiotepa (300 mg/m2), and ATG (40 mg/kg) was followed by transplantation of purified CD34+ stem cells harvested from peripheral blood mononuclear cells. The patients in cases 2 and 3 attained complete remission without any medication. Thus for patients with refractory JRA, autologous CD34+ cell transplantation appears to be a safe and feasible choice of treatment in terms of good quality of life. However, a greater number of patients and a longer observation period are needed before definitive conclusions can be drawn.
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Artritis Juvenil/terapia , Enfermedades Autoinmunes/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Enfermedades Autoinmunes/tratamiento farmacológico , Preescolar , Terapia Combinada , Trasplante de Células Madre de Sangre del Cordón Umbilical , Resultado Fatal , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Inducción de Remisión , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante HomólogoRESUMEN
We report the case of 13-year-old boy who had been diagnosed as having anaplastic large cell lymphoma (ALCL) when he was 11 years old. He suffered a relapse despite the chemotherapy regimens he had been subjected to. Since anaplastic lymphoma kinase (ALK), one of the important prognostic factors of ALCL, was not expressed in the tumor cells, allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched elder brother was performed. Eleven months after PBSCT, the patient developed nephrotic syndrome as a consequence of chronic graft-versus-host disease (GVHD). He was diagnosed as having membranous nephropathy (MN) based on the results of histological examinations. Soluble interleukin-2 receptor and anti-nuclear antibody closely reflected the clinical course of MN, therefore some immune mechanisms closely related to chronic GVHD seemed to contribute to the occurrence of MN after PBSCT.
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Glomerulonefritis Membranosa/etiología , Linfoma de Células B Grandes Difuso/terapia , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Adolescente , Enfermedad Injerto contra Huésped/etiología , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Masculino , Trasplante HomólogoRESUMEN
Newly diagnosed children with ALL (n=32) were treated on a protocol incorporating minimal residual disease (MRD)-based treatment decisions. MRD was monitored at 4 time points by semi-quantitative PCR detection of antigen receptor gene rearrangement, flow cytometry, quantitative RT-PCR detection of chimeric gene transcripts and overexpressed WT1 mRNA. Four patients positive for MRD at week 5 were treated with an intensified regimen. Median follow-up was 5.0 years (range 3.8-6.6 years) with a 4-year event-free survival rate of 93.8+/-4.3%. This MRD-based treatment strategy seems to be highly successful and may improve the outcomes of children with ALL. A large study is warranted.
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Biomarcadores de Tumor/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Antineoplásicos/uso terapéutico , Niño , Preescolar , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Resultado del TratamientoRESUMEN
Although infants with acute lymphoblastic leukemia (ALL) and a germline MLL gene have a better prognosis than comparable infants with a rearranged MLL gene, their optimal therapy is controversial. In 2 consecutive studies, conducted between 1996 and 2002, we treated 22 cases of infant ALL with germline MLL using chemotherapy alone. The 5-year event-free survival rate was 95.5% with a 95% confidence interval of 86.9 to 100%. All 21 infants with precursor B-cell ALL have been in first complete remission for 3.5 to 8.8 years. Most treatment-related toxicities were predictable and well tolerated, and neither secondary malignancies nor physical growth impairments have been observed. These results indicate that chemotherapy of the type described here is both safe and highly effective against infant precursor B-cell ALL with MLL in the germline configuration.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Burkitt/tratamiento farmacológico , Proteína de la Leucemia Mieloide-Linfoide , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma de Burkitt/genética , Linfoma de Burkitt/mortalidad , Supervivencia sin Enfermedad , Femenino , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Japón , Masculino , Proteína de la Leucemia Mieloide-Linfoide/genética , Inducción de Remisión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The authors describe a boy with Wiskott-Aldrich syndrome (WAS) who was diagnosed immediately after birth using flow cytometric and genetic analysis. At 1 year of age he received unrelated cord blood stem cell transplantation (UCBSCT); however, the sex chromosomes of the peripheral blood mononuclear cells showed that the recipient type was over 70%. This rate gradually increased to over 90% after immunosuppressant therapy was discontinued. Clinical manifestations, including high fever, graft-versus-host disease (GVHD)-like eruptions, and signs of infection recurred. Results of flow cytometric and genetic analysis of mononuclear cells from the boy's mother were normal with no mutation. Three months after UCBSCT, he received an unmanipulated HLA-haploidentical 2-locus-mismatched bone marrow transplant (BMT) from his mother. The prophylaxis against GVHD was tacrolimus and short-term methotrexate. Hematopoietic reconstitution was rapid and fluorescence in situ hybridization analysis revealed sustained engraftment. Grade II acute GVHD developed but improved rapidly with the administration of methylprednisolone. The patient is progressing well and displays complete chimerism 2 years after the BMT. This case suggests that unmanipulated haploidentical BMT from the mother might be feasible not only for malignant disease but also for immunodeficiency disease patients who urgently need stem cell transplants and have no HLA-identical donors.
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Trasplante de Médula Ósea , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped/prevención & control , Síndrome de Wiskott-Aldrich/terapia , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA/metabolismo , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Madres , Resultado del TratamientoRESUMEN
When regulation of GCR1 expression was analysed using a GCR1-lacZ fusion, lacZ expression levels were decreased in the Deltagcr1 or Deltagcr2 mutant. RT-PCR analysis of genomic GCR1 transcript confirmed the dependency of GCR1 expression on the Gcr1p-Gcr2p complex. Examination of the 5' non-coding region of GCR1 identified three putative Gcr1p binding sites (CT-boxes) in the -100 to -200 region of GCR1, and the putative binding sites for Rap1p (RPG-box) and Abf1p were also identified nearby. The region containing putative cis-elements was analysed by cloning it upstream of the CYC1TATA-lacZ fusion. The GCR1(UAS)-CYC1TATA-lacZ fusion showed a moderate activity and, as expected, the activity was drastically reduced in the Deltagcr1 or Deltagcr2 mutant. Systematic deletion and mutation analyses of cis-elements in this region demonstrated that the putative binding sites for Rap1p and Abf1p were not involved in the promoter activity of GCR1(UAS) and only one of the three CT-boxes showed GCR1- and GCR2-dependent promoter activity. In contrast to the expression of glycolytic genes, where a RPG-box adjacent to the CT-box is required for strong promoter activities, CT-box-dependent expression of GCR1 did not require the RPG-box. Also, a contribution of Sgc1p, an E-box binding transcription factor, to the expression of GCR1 was suggested, based on its disruption analysis.
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Proteínas de Unión al ADN/biosíntesis , Proteínas Fúngicas/biosíntesis , Regulación Fúngica de la Expresión Génica/fisiología , Saccharomyces cerevisiae/metabolismo , Secuencia de Bases , Sitios de Unión/fisiología , Clonación Molecular , Proteínas de Unión al ADN/genética , Proteínas Fúngicas/genética , Glucólisis/fisiología , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas/fisiología , ARN de Hongos/química , ARN de Hongos/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Complejo Shelterina , Proteínas de Unión a Telómeros/metabolismo , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética/fisiologíaRESUMEN
UNLABELLED: Sclerosing mediastinitis is a very rare benign disorder characterised by the development of dense fibrous tissue within the mediastinum. Affected patients are typically young adults with infant cases being uncommon especially in areas without endemic histoplasmosis. We report a Japanese boy with markedly elevated serum inflammatory markers for more than 1 year in the absence of any clinical manifestations. 67Ga-scintigraphy demonstrated an accumulation in the mediastinal region and an open biopsy revealed a hard fibrous mass in the anteriosuperior mediastinum. Thus, a diagnosis of idiopathic sclerosing mediastinitis was made. CONCLUSION: To the best of our knowledge, this case is the youngest patient reported with this disorder. In patients with mediastinal mass lesions the diagnosis of sclerosing mediastinitis should be considered as well as infectious, autoimmune or neoplastic disease even in children.
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Mediastinitis/diagnóstico , Mediastino/patología , Anemia/etiología , Pueblo Asiatico , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Niño , Humanos , Inmunoglobulina G/sangre , Japón , Masculino , Mediastinitis/cirugía , Mediastino/diagnóstico por imagen , Mediastino/cirugía , Cintigrafía , EsclerosisRESUMEN
In the yeast two-hybrid system, the N-terminal region of Rap1p was shown to interact with Gcr1p and Gcr2p. Disruption of gcr1 and/or gcr2 in the two-hybrid reporter strain demonstrated that the interaction with Gcr1p does not require Gcr2p, whereas the interaction with Gcr2p is mediated through Gcr1p. Deletion of the N-terminal region of Rap1p alone did not show a growth phenotype, but a growth defect was observed when this mutation was combined with a gcr2 deletion. The poor growth of the gcr1 null mutant was not affected further by the N-terminal deletion of Rap1p, but the growth of gcr1 strains with mutations in the DNA binding region of Gcr1p was affected by the removal of the N-terminal region of Rap1p. These results suggest that one function of the N-terminal region of Rap1p, presumably the BRCT domain, is to facilitate the binding of Gcr1p to the promoter by a protein-protein interaction.
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Proteínas de Unión al ADN/metabolismo , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica/fisiología , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Unión a Telómeros/metabolismo , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional/fisiología , Western Blotting , ADN de Hongos/genética , ADN de Hongos/metabolismo , Proteínas de Unión al ADN/genética , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica/genética , Mutagénesis , ARN de Hongos/química , ARN de Hongos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Complejo Shelterina , Proteínas de Unión a Telómeros/genética , Transactivadores/genética , Factores de Transcripción/genética , Activación Transcripcional/genética , Técnicas del Sistema de Dos HíbridosRESUMEN
PURPOSE: To determine the dose-limiting toxicity, maximum tolerated dose, and potential efficacy of irinotecan in children with refractory malignant solid tumors. PATIENTS AND METHODS: In the present phase I clinical trial, 28 patients received irinotecan 50 to 200 mg/m2 per day by intravenous 2-hour infusion over the course of 3 days, repeated once after an interval of 25 days. Fifty-one treatment courses were administered to these patients. RESULTS: Dose-limiting toxicities were observed at the dose of 200 mg/m2 per day for 3 days. Diarrhea and hematopoietic toxicities were the dose-limiting factors, and the former required support with intravenous fluid administration. The occurrence of vomiting was variable. Decreases in clinical tumor marker levels were observed in the majority of patients who received two cycles of irinotecan 80 mg/m2 per day to 200 mg/m2 per day over the course of 3 days, and partial response was attained in four patients who received irinotecan in two cycles of 140 mg/m2 per day to 200 mg/m2 per day over the course of 3 days. Pharmacokinetic studies showed that the plasma concentration of irinotecan and its active metabolite SN-38 ranged from 93 to 2,820 ng/mL and 5.2 to 34.8 ng/mL, respectively, during 3-day infusions of irinotecan 200 mg/m2 per day. The mean clearance of irinotecan was 14.54 L/h per m2 (range 8.45-20.83 L/h per m2). CONCLUSION: The maximum tolerated dose was determined to be a dose of irinotecan between 160 mg/m2 per day and 180 mg/m2 per day administered over the course of 3 consecutive days on an inpatient basis, repeated once after 25 days off, and our results indicate that irinotecan is a promising anticancer agent that is worthy of phase II trials in pediatric solid tumors.