Expression of cyclin A in human leukemia cell line HL-60 following treatment with doxorubicin and etoposide: the potential involvement of cyclin A in apoptosis

We investigated expression of cyclin A in HL-60 cells after induction of apoptosis with doxorubicin and etoposide. Following apoptotic trigger, both cells arrested in G2/M phase of the cell cycle and changes in morphology were noticed. Moreover, compared to control, the number of cells with cyclin A expression was changed and translocation of this protein from the nucleus to the cytoplasm was observed. The decrease in the number of cells with cyclin A expression, followed by the increase, and cyclin A distribution throughout the cell, appeared to be dose-dependent. Cells treated with lower doses of doxorubicin and etoposide as well as the untreated cells were found to have cyclin A scattered mainly throughout the nucleus. However, immunogold labeling of cyclin A in both cell lines treated with 5- and 10-microM doses of doxorubicin, and 20 and 200 microM of etoposide was observed more often in the cytoplasm than in the nucleus. Cells with features of apoptosis with bodies resembling micro-nuclei labeled with gold particles for cyclin A were recognized. However, the small amount of giant cells was also seen. These results suggest that cyclin A expression is linked to cell death pathways.     

Mutations in the human laminin β2 (LAMB2) gene and the associated phenotypic spectruma

Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin β2, which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease‐causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome. Although truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N‐terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist. Hum Mutat 31:992–1002, 2010. © 2010 Wiley‐Liss, Inc.     

Estimation of the Potential Antitumor Activity of Microencapsulated Lactobacillus acidophilus Yogurt Formulation in the Attenuation of Tumorigenesis in Apc(Min/+) Mice

There is a strong correlation between orally administered probiotics and suppression of the low-grade inflammation that can lead to restoration of normal local immune functions. We studied the potential immunomodulatory and antitumorigenic properties of microencapsulated probiotic bacterial cells in a yogurt formulation in Min mice carrying a germline APC mutation. Daily oral administration of microencapsulated Lactobacillus acidophilus bacterial cells in the yogurt formulation mice resulted in significant suppression of colon tumor incidence, tumor multiplicity, and reduced tumor size. Results show that oral administration of microencapsulated L. acidophilus contributed to the stabilization of animal body weight and decreased the release of bile acids. Histopathological analyses revealed fewer adenomas in treated versus untreated animals. Furthermore, treated animals exhibited fewer gastrointestinal intra-epithelial neoplasias with a lower grade of dysplasia in detected tumors. Results suggest that oral administration of microencapsulated probiotic L. acidophilus exerts anti-tumorous activity, which consequently leads to reduced tumor outcome.     

Methods of coping with neoplastic disease in men with non-muscle-invasive bladder cancer

Only limited data evaluating coping methods in patients with bladder cancer are available in the literature. Also, it is unclear how the mental status of these patients affects their stress coping strategies. The aim of the study was to evaluate the stress coping strategies in patients with non-muscle-invasive bladder cancer (NMIBC) and to assess the impact of sociodemographic factors, presence of anxiety and depressive symptoms and degree of sexual satisfaction on stress coping strategies. This prospective cohort study included 100 male patients qualified for control cystoscopy who underwent at least one transurethral resection of bladder tumour (TURB) procedure in the past for NMIBC and at least one control cystoscopy. The minimal follow-up period after primary TURB was 1 year. The MiniCOPE, the Hospital Anxiety and Depression Scale and the Sexual Satisfaction Questionnaire were used. The questionnaires were completed anonymously before cystoscopy in a room that provided privacy. Majority patients with NMIBC chosen adaptive strategies, with ‘accepting’ and ‘seeking emotional support’ being the most common. The choice of strategy was influenced by the severity of anxiety and depressive symptoms as well as the level of sexual satisfaction and pain sensations. Also, sociodemographic variables, such as marriage status, progeniture or the level of education played a role in strategy selection. The results of this study indicate that patients with NMIBC choose adaptive stress coping strategies. It also provides a better understanding of the impact of various aspects of mental health in patients with NMIBC on coping with stress. Each patient treated for NMIBC should undergo appropriate psychological and sociodemographic evaluation, which will allow easier identification of patients at high risk of treatment and postoperative surveillance discontinuation.     

Anatomical predictors for suture-based closure of the patent foramen ovale: A multicenter experience

Background

NobleStitch EL is a novel suture-based technique used for patent foramen ovale (PFO) closure and an alternative to traditional double-disc devices without the need for antithrombotic therapy. However, successful closure rates are still unknown, and certain anatomies may be unfavorable for successful closure.

Aims

We assessed the efficacy of the NobleStitch EL and sought to identify patient-related anatomical features associated with successful suture-based closure.

Methods

We included 55 patients who underwent PFO closure with the NobleStitch EL in The Netherlands and Switzerland. Successful closure was defined as residual right-to-left shunt grade ≤1 with Valsalva maneuver at a cardiac ultrasound. Predefined possible anatomical determinants for effective closure included PFO length, atrial septal aneurysm, PFO entry- and exit diameter.

Results

Successful closure was achieved in 33 patients (60%). The PFO length was shorter in patients with successful closure compared to unsuccessful closure with a median length of 9.6 mm (IQR 8.0–15.0) versus 13.3 mm (IQR 11.4–18.6) on preprocedural ultrasound (p = 0.041) and 9.9 mm (IQR 8.0–13.1) versus 12.5 mm (IQR 9.7–15.4) on angiography (p = 0.049). Additionally, the PFO exit diameter and PFO volume were smaller in patients with successful closure than unsuccessful closure, with a mean diameter of 7.0 ± 3.1 mm versus 9.5 ± 3.8 mm (p = 0.015) and a median volume of 381 mm³ (IQR 286–894) versus 985 mm³ (IQR 572–1550) (p = 0.016).

Conclusion

In our study cohort, the successful PFO closure rate using NobleStitch EL was relatively low (60%). With this alternative procedure, patients with a small PFO driven by a short PFO tunnel length and small exit diameter seem to be eligible for successful suture-based closure.     

Retrospective confidence judgments: Meta‐analysis of functional magnetic resonance imaging studies

Confidence in our retrieved memories, that is, retrospective confidence, is a metamemory process we perform daily. There is an abundance of applied research focusing on the metamemory judgments and very diverse studies including a wide range of clinical populations. However, the neural correlates that support its functioning are not well defined impeding the implementation of noninvasive neuromodulatory clinical interventions. To address the neural basis of metamemory judgments, we ran a meta‐analysis, where we used the activation likelihood estimation method on the 19 eligible functional magnetic resonance imaging studies. The main analysis of retrospective confidence revealed concordant bilateral activation in the parahippocampal gyrus, left middle frontal gyrus, and right amygdala. We also run an analysis between the two extreme levels of confidence, namely, high and low. This additional analysis was exploratory, since the minimum amount of articles reporting these two levels was not reached. Activations for the exploratory high > low confidence subtraction analysis were the same as observed in the main analysis on retrospective confidence, whereas the exploratory low > high subtraction showed distinctive activations of the right precuneus. The involvement of the right precuneus emphasizes its role in the evaluation of low confidence memories, as suggested by previous studies. Overall, our study contributes to a better understanding of the specific brain structures involved in confidence evaluations. Better understanding of the neural basis of metamemory might eventually lead to designing more precise neuromodulatory interventions, significantly improving treatment of patients suffering from metamemory problems.