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81.
Summary Leukocyte-derived inhibitory activity inhibiting the entry of normal progenitor cells of granulocytes and macrophages (CFU-GM) into the S-phase of a cell cycle was investigated in 16 patients with different forms of myelodysplastic syndrome (MDS). The presence of this inhibitory activity was analysed in medium conditioned with low-density cells obtained from peripheral blood of MDS patients. The inhibition rate was measured by 3H-thymidine suicide technique with subsequent cultivation of pretreated cells in semisolid agar medium. Low-density cells from MDS patients of various types were studied: from the twelve patients with refractory anaemia (RA or RAS) only three were positive, one patient with chronic myelomonocytic leukaemia (CMML) was negative while one patient with refractory anaemia with excess of blasts (RAEB) and two patients with RAEB in transformation (RAEB-T) were positive with respect of the described test. In two patients with RA, who underwent a long-term investigation, the production of leukocyte-derived inhibitory activity preceded the development of disease into RAEB or RAEB-T. In five positive cases, supernatants were incubated with antiserum against human placental ferritin; with one exception, the inhibitory activity was neutralized. 相似文献
82.
Background
The social–ecological environment of undocumented children of migrant workers includes varying levels of risk factors. Growing up in these conditions compromises children’s development on all levels. Many of these children are in need of psychotherapy, however, due to limited resources, only a few of them receive mental health aid.Objective
The present research undertook to construct and examine the effectiveness of a specialized group intervention program to enhance children’s self-efficacy and mental health.Methods
Participants were 70 children aged 8–12 of illegal migrant workers in Israel. The repeated measures design included completion of a self-efficacy scale and emotional, behavioral and social difficulties child-report and teacher-report measures. Children were randomly allocated to either an intervention or control group.Results
The first hypotheses predicting a greater improvement in self-efficacy between the pre-test and post-test for children in the intervention as opposed to control group was confirmed. The second hypothesis predicting a greater reduction in the self- and teacher-reports of emotional, social and behavioral difficulties was confirmed. The third hypothesis predicting a moderating relation between self-efficacy, group type and time on the dependent variables was confirmed only for children’s self-report of their difficulties.Conclusions
Findings provide evidence for the effectiveness of this short term playful intervention program for this group of disadvantaged children, suggesting its application to other at-risk groups of children. 相似文献83.
José Joaquín Mira PhD Mercedes Guilabert PhD Virtudes Pérez‐Jover PhD Susana Lorenzo MD MPH PhD 《Health expectations》2014,17(6):826-839
Background
There are doubts on whether patients feel that they have sufficient information for actively participating in clinical decisions.Objective
To describe the type of information that patients receive. To determine whether patients consider this information sufficient, and whether it contributes or not to improve clinical safety. To identify the barriers for patient participation in clinical decision making.Study Design
Cross‐sectional study with 764 patients and 327 physicians.Study Setting and participants
Fourteen health centres belonging to three primary care districts and three hospitals in Spain.Principal Findings
Just 35.1% (268) (95% CI 32.2, 39.1%) of patients preferred to have the last word in clinical decisions. Age (39 vs. 62%, P < 0.001) and severity of illness (38 vs. 46%, P = 0.002) increased the tendency to take a passive role. In 85.1% (650) (95% CI 83.3, 88.3%) of the cases, patients reported having received sufficient information. Lack of consultation time (29.6%, 95% CI 25.8, 32.5%) and patients'' use of Internet or other sources (19.2%, 95% CI 16.4, 22.2%) were identified as new obstacles to doctor–patient communication by the patients. Only 19.6% (64) (95% CI 15.4, 24.2%) of doctors considered that they could intervene to involve patients in the decisions.Discussions and Conclusions
The majority of patients prefer the decisions to be made by their doctor, especially those with more severe illnesses, and older patients. Patients are not normally informed about medication interactions, precautions and foreseeable complications. The information provided by general practitioners does not seem to contribute enough to the patient involvement in clinical safety. 相似文献84.
Hee Jeong Yoo So Young Yang In Hee Cho Mira Park Soon Ae Kim 《Psychiatry investigation》2014,11(3):319-324
Objective
Autism spectrum disorders (ASDs) are a group of early childhood-onset neurodevelopmental disorders characterized by deficits in social interaction and language skills, and repetitive behaviors. Brain-derived neurotrophic factor (BDNF) plays a critical role in the differentiation of normal neuronal cells during embryonic and postnatal neuronal development through its neurotrophic effects.Methods
In this study, we performed a family-based association test (FBAT) between single nucleotide polymorphisms (SNPs; rs6265, rs11030101, rs7103411, and rs7103873) or haplotypes in the BDNF gene and affection status or several quantitative traits characterized by ADI-R with151 Korean trios, including a child diagnosed as ASDs.Results
While no significant association was found between SNPs or haplotypes and the ASDs disease status, a quantitative transmission disequilibrium test (QTDT) by using quantitative traits identified associations of the SNPs (rs6265 and rs11030101) with a domain score for "Restricted, Repetitive and Stereotyped patterns of behavior" (C domain), especially at the subdomain scores for "encompassing preoccupation or circumscribed pattern of interest" (C1) (rs6265A allele, dominant model, p-value=0.019; rs11030101 A allele, additive model, p-value=0.015) and "preoccupations with part of objects or non-functional elements of material" (C4) (rs11030101 A allele, additive model, p-value=0.015) within the ADI-R diagnostic algorithm. In addition, significant associations were also identified between the haplotypes and these quantitative traits (C1, p-value=0.016; C4, p-value=0.012).Conclusion
We conclude that BDNF gene polymorphisms have a possible role in the pathogenesis of ASDs. 相似文献85.
86.
87.
Central nervous system infection and sepsis are the most frequently observed clinical presentations of listeriosis infection; however, they are rare in immunocompetent children beyond the neonatal period. In the presented case, we described gastrointestinal involvement, subacute meningitis, sinusitis and sepsis in a two-year-old previously healthy child with acute infection caused by Listeria monocytogenes. We suggest that the infection was probably enhanced by an inappropriate corticosteroid treatment at the onset of the disease, while immunological testing did not confirm the primary deficiency of cellular immunity. 相似文献
88.
89.
Adhesive capsulitis is, in most cases, a self-limiting condition of poorly understood etiology that results in shoulder pain and large mobility deficits. The socio-economic burden will increase as with continuous aging of our population. In addition, both prevalence and incidence figures of adhesive capsulitis are increasing. No literature overview solely focuses on the physiotherapeutic options in patients with adhesive capsulitis and their scientific evidence. Moreover, although some physiotherapeutic interventions show evidence regarding reducing pain or increasing mobility, there is little evidence to suggest that the disease prognosis is affected and this raises the need for new, innovative research in the area of adhesive capsulitis and its treatment. By presenting its current evidence, we hope to retrieve several gaps in the present management of adhesive capsulitis by physiotherapists and provide us with new insights for improving the physiotherapists' policy in treating adhesive capsulitis patients, e.g., continuously increasing nociceptive impulse activity, as in early stages of adhesive capsulitis, could lead to peripheral and subsequently long-lasting central sensitization, as well as to an increased activity of the sympathetic nervous system. But up to now the involvement of central sensitization in adhesive capsulitis has not been studied yet and remains speculative. Finally, when selecting a physical treatment method for adhesive capsulitis, it is extremely important to consider the patient's symptoms, stage of the condition, and recognition of different patterns of motion loss. Guidelines for clinical assessment will be presented in this scoping review. 相似文献
90.
Thomas Hartmann Xinsong Xu Mira Kronast Susanne Muehlich Kathleen Meyer Wolfgang Zimmermann Jerard Hurwitz Zhen-Qiang Pan Stefan Engelhardt Antonio Sarikas 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(9):3371-3376
Simian virus 40 (SV40) large tumor antigen (LT) triggers oncogenic transformation by inhibition of key tumor suppressor proteins, including p53 and members of the retinoblastoma family. In addition, SV40 transformation requires binding of LT to Cullin 7 (CUL7), a core component of Cullin-RING E3 ubiquitin ligase 7 (CRL7). However, the pathomechanistic effects of LT–CUL7 interaction are mostly unknown. Here we report both in vitro and in vivo experimental evidence that SV40 LT suppresses the ubiquitin ligase function of CRL7. We show that SV40 LT, but not a CUL7 binding-deficient mutant (LTΔ69–83), impaired 26S proteasome-dependent proteolysis of the CRL7 target protein insulin receptor substrate 1 (IRS1), a component of the insulin and insulin-like growth factor 1 signaling pathway. SV40 LT expression resulted in the accumulation and prolonged half-life of IRS1. In vitro, purified SV40 LT reduced CRL7-dependent IRS1 ubiquitination in a concentration-dependent manner. Expression of SV40 LT, or depletion of CUL7 by RNA interference, resulted in the enhanced activation of IRS1 downstream signaling pathways phosphatidylinositol-3-kinase/AKT and Erk mitogen-activated pathway kinase, as well as up-regulation of the downstream target gene c-fos. Finally, SV40 LT-positive carcinoma of carcinoembryonic antigen 424/SV40 LT transgenic mice displayed elevated IRS1 protein levels and activation of downstream signaling. Taken together, these data suggest that SV40 LT protects IRS1 from CRL7-mediated degradation, thereby sustaining high levels of promitogenic IRS1 downstream signaling pathways.Studies with simian virus 40 (SV40), a member of the Polyomaviridae family of tumor viruses, have led to fundamental insights into molecular processes of cell transformation and oncogenesis (1, 2). SV40 encodes the large tumor antigen (LT) with the potential to transform cells in culture and induce tumors in rodents. The tumorigenic features of SV40 have been attributed to binding and deactivation of key tumor suppressor proteins of the host cell including p53 and members of the retinoblastoma (pRB) family (1–3). In addition, SV40 LT was shown to be physically associated with Cullin 7 (CUL7; also named p185 or p193) (4, 5) as well as insulin receptor substrate 1 (IRS1) (6). It has been proposed that the association of SV40 LT with either CUL7 or IRS1 is critical to SV40 oncogenic transformation (7–9). However, the functional effect of LT interaction with CUL7/IRS1 and their pathophysiological interrelation remains mostly unknown.CUL7 is a scaffold protein responsible for assembling the multisubunit Cullin-RING E3 ubiquitin ligase 7 (CRL7) that consists of the RING-finger protein ROC1 and the Skp1-Fbw8 substrate-targeting subunit (10, 11). Genetic studies documented a pivotal growth-regulatory role of CRL7. Both cul7 (12) and fbw8 (13) null mice exhibit intrauterine growth retardation. In addition, CUL7 germ-line mutations were linked to 3-M syndrome, a hereditary disorder characterized by pre- and postnatal growth retardation in humans (14, 15), as well as Yakut dwarfism syndrome (16). DeCaprio and colleagues mapped the CUL7 interaction domain on SV40 LT to residues 69–83 and demonstrated that the CUL7 binding-deficient deletion mutant (LTΔ69–83) lost its transformation potential despite maintaining its ability to bind and inactivate p53 and pRB members (8, 9). This suggested that CUL7 may act as a tumor suppressor and that constraining growth-inhibitory functions of CRL7 may be critical to SV40 transformation.We previously identified IRS1, a component of the insulin and insulin-like growth factor 1 (IGF1) signaling pathway, as a proteolytic target of CRL7 (17). Binding of insulin or IGF1 to its receptor induces tyrosine phosphorylation of IRS1 and subsequent activation of phosphatidylinositol-3-kinase (PI3K)/AKT and Erk mitogen-activated pathway kinase (MAPK) pathways (18). It was shown that CRL7-induced degradation of IRS1 is part of a negative feedback loop via mechanistic target of rapamycin complex 1 (mTORC1) to restrain IRS1 downstream signaling (17, 19). A more recent study suggested an mTORC2-dependent feedback inhibition of IRS1 by direct phosphorylation of Fbw8, resulting in enhanced stability of this F-box protein that promotes IRS1 degradation (20). Collectively, these studies have implicated roles for CRL7 in regulating both mTORC1 and mTORC2 signaling. Based on the above observations, we investigated whether SV40 LT impacts on CRL7 feedback regulation of IRS1 signaling in addition to its effects on p53 and pRB members. 相似文献