Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.

BACKGROUND: The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector. RESULTS: Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents. CONCLUSIONS: We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.     

Intraneural Growth of a Capillary Haemangioma of the Cauda Equina

Solitary intraneural haemangiomas are very rare. A case of intraneural capillary haemangioma involving two nerve roots of the cauda equina is reported. The patient was a 63-year-old woman with a three years history of intermittent lumbalgia and numbness of the ventral surface of the left thigh. Magnetic resonance imaging detected an intradural extramedullary nodular space occupying mass at the level of the conus medullaris. Laminectomy of T12 and complete removal of the tumour were performed. Histopathological analysis demonstrated a capillary haemangioma. The tumour was located within the sheaths of a spinal nerve root. The lesion consisted of a myriad of small and very small vessels, reticularly arranged with normal nerve fascicles dispersed within the nodules of clustered capillaries. The present case of an intraneural capillary haemangioma of the cauda equina appears to be one of the first reported examples of this entity in the world's literature. The clinical presentation, diagnostic procedures and therapeutic options of intraneural haemangiomas of the conus medullaris and cauda equina are discussed. The current literature is reviewed.     

Genitalverstümmelung und Strafrecht

Some of the girls who live in Germany and have Muslim parents are threatened by female genital mutilation. This report describes the kinds and medical consequences of female genital mutilation as well as the criminal judgement. Female genital mutilation is considered as dangerous bodily harm, not as grievous bodily harm. Consent does not justify the infringement of rights. The argument that Islam justifies the infringement of rights is irrelevant by law. The human right of bodily intactness has priority over the right of religious freedom. Finally the legal regulations about dealing with personal data are presented. A legal compulsory registration still does not exist.     

Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade: a study with FDG positron emission tomography/magnetic resonance imaging coregistration and image fusion.

PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.     

Effects of Particulate Matter on Cytokine Production In Vitro: A Comparative Analysis of Published Studies

In recent years evidence has accumulated indicating that airborne particles cause adverse health effects. To understand the underlying mechanisms, a multitude of in vitro studies have been performed focusing on inflammatory responses, especially cytokine production. However, the diversity of studies renders it difficult to determine which results are consistent and which exposures most effective. The present review thus aimed to perform a comparative analysis of the available data. Forty-nine studies dealing with in vitro effects of particles on cytokine production in bronchial epithelial or related cells and monocytes/macrophages were included. Twenty-eight studies investigated epithelial cells and could be categorized according to specific combinations of exposure level and time, and 27 dealt with monocytes/macrophages. Eight studies provided further data using non-compatible exposure modes. The most common finding was that particles significantly induced cytokine production in both epithelial cells and monocytes/macrophages at concentrations of 50–100 μg/mL and exposure times of 9–24 h. The effects did not appear to be significantly different between cell or particle types. There were virtually no effects reported below 10 μ g/mL, but these levels were used in only a few studies. Thus, the available data demonstrate that cytokine measurements are sensitive enough to assess cell activation after particle exposure in vitro, yielding relatively consistent results across cell types. However, since the majority of data refers to high particle load compared to in vivo conditions, future studies should consider more sensitive assays, multivariate panels describing the cell's regulatory state, interactions between cell types, and second-line outcome measures that are close to clinically observed effects.     

The perception of the Illness with Subsequent Outcome Measure in More Favorable in Continuos Peritoneal Dialysis vs Hemodialysis in the Framework of Appraisal Model of Stress

The aim of the study was to use the appraisal model of stress to compare hemodialysis (HD) and continuous peritoneal dialysis (CAPD) patients with special focus on the perception of end-stage renal disease and subsequent emotional profile and health related quality of life (HQoL) in. We hypothesize that different circumstances related to both modes of therapies will result in dissimilar perception of chronic illness with subsequent changes in emotional profile and heath related quality of life. The total of 88 patients with end stage renal disease (ESRD) enrolled in hemodialysis (n=52; HD) or continuous peritoneal dialysis (n=36; CAPD) were given a battery of psychological tests: The Profile of Mood States, The Nottingham Health Profile, The Stress Situation Assessment Questionnaire, The Social Appreciation Questionnaire and The Situation and Trait and Anxiety Inventory. All patients perceived ESRD in terms of a loss and a threat. Moreover, CAPD patients evaluated ESRD as a challenge. Despite different perception of ESRD no significant difference in the level of fear, anxiety or emotional profile was found. Both HD and CAPD patient were reported more fatigue/inertia and confusion/bewilderment than control groups. The main health related complaints were similar in both ESRD patients with major complaints of sleeping disturbances, motor limitations and lack of energy. From the psychological point of view, CAPD treatment seems more like challenge to the enrolled patient which is positive outcome. Despite different appraisal of stress mood and health related complaints were similar in both groups. This may be a result of optimal regulation of cognitive perception of the stress depending on the circumstances of therapy.     

Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.