Incidental MALT Type Lymphoma Exhibiting Prominent Plasma Cell Differentiation Associated with Hashimoto’s Thyroiditis. A Two Case Report

We present here two cases of incidental extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) showing prominent plasma cell differentiation associated with Hashimoto’s thyroiditis (HT). Histological examination demonstrated that both lesions exhibited HT including lymphoplasmacytic infiltration with the formation of germinal centers, destruction of the normal thyroid follicular architecture, Hürthle cell changes, and squamous metaplasia. The dominant tumor nodules of both cases contained large, well-circumscribed but unencapsulated aggregation of mature plasma cells and scattered centrocyte-like cells (CCL-cells). Both lesions contained a few lymphoepithelial lesions. Moreover, immunohistochemical study demonstrated that plasma cells and CCL-cells of these two lesions contained monotypic intracytoplasmic kappa light chain. Other small B-cell lymphomas, plasmacytoma and plasmablastic lymphoma were excluded using stains for CD5, CD10, CD23, CD43, CD56. Cyclin D1, human herpes virus type-8

Stochasticity of flow through microcirculation as a regulator of oxygen delivery

<p>Abstract</p> <p>Objective</p> <p>Observations of microcirculation reveal that the blood flow is subject to interruptions and resumptions. Accepting that blood randomly stops and resumes, one can show that the randomness could be a powerful means to match oxygen delivery with oxygen demand.</p> <p>Method</p> <p>The ability of the randomness to regulate oxygen delivery is based on two suppositions: (a) the probability for flow to stop does not depend on the time of uninterrupted flow, thus the number of interruptions of flow follows a Poisson distribution; (b) the probability to resume the flow does not depend on the time for flow being interrupted; meaning that time spent by erythrocytes at rest follows an exponential distribution. Thus the distribution of the time to pass an organ is a compound Poisson distribution. The Laplace transform of the given distribution gives the fraction of oxygen that passes the organ.</p> <p>Result</p> <p>Oxygen delivery to the tissues directly depends on characteristics of the irregularity of the flow through microcirculation.</p> <p>Conclusion</p> <p>By variation of vasomotion activity it is possible to change delivery of oxygen to a tissue by up to 8 times.</p

Some Like It Fat: Comparative Ultrastructure of the Embryo in Two Demosponges of the Genus Mycale (Order Poecilosclerida) from Antarctica and the Caribbean

0000-0002-7993-1523© 2015 Riesgo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Ensemble-Based Computational Approach Discriminates Functional Activity of p53 Cancer and Rescue Mutants

The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain (“cancer mutants”). Activity can be restored by second-site suppressor mutations (“rescue mutants”). This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD), without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC) metric was strongly correlated (r2 = 0.77) with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i) p53 cancer mutants were more flexible than wild-type protein, (ii) second-site rescue mutations decreased the flexibility of cancer mutants, and (iii) negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants

Constitutive expression of CD26/dipeptidylpeptidase IV on peripheral blood B lymphocytes of patients with B chronic lymphocytic leukaemia

We have investigated the expression of the ectoenzyme dipeptidylpeptidase IV (DPP IV)/CD26 on lymphocytes obtained from patients with B chronic lymphocytic leukaemia (B-CLL) and compared it with healthy subjects. Using two-colour immunofluorescence analysis with CD26 and CD20 or CD23 monoclonal antibodies, CD26 was found undetectable on peripheral resting B-cells (CD20+ CD23−) from normal donors whereas it was expressed on B-cells activated in vitro with interleukin (IL)-4 and Staphylococcus aureus strain cowan I (CD20+ CD23+). The expression of CD26 on leukaemic B-cells (CD20+ CD23+) was clearly induced in 22 out of 25 patients examined. Consequently, induced levels of CD26 cell surface expression on either normal activated and malignant B-cells coincided with the enhancement of DPP IV activity detected on the surface of these cells. Reverse transcription polymerase chain reaction analyses showed that the transcript levels of the CD26 gene was higher in normal activated B-cells and B-CLL cells than in resting B-cells, suggesting that CD26 was expressed at the level of transcriptional activation. These observations provide evidence of the abnormal expression of DPPIV/CD26 in B-CLL which, therefore, may be considered as a novel marker for B-CLL. Further investigation in relation to CD26 expression and other B malignancies needs to be defined. © 1999 Cancer Research Campaig

Understanding the Origins of Bacterial Resistance to Aminoglycosides through Molecular Dynamics Mutational Study of the Ribosomal A-Site

Paromomycin is an aminoglycosidic antibiotic that targets the RNA of the bacterial small ribosomal subunit. It binds in the A-site, which is one of the three tRNA binding sites, and affects translational fidelity by stabilizing two adenines (A1492 and A1493) in the flipped-out state. Experiments have shown that various mutations in the A-site result in bacterial resistance to aminoglycosides. In this study, we performed multiple molecular dynamics simulations of the mutated A-site RNA fragment in explicit solvent to analyze changes in the physicochemical features of the A-site that were introduced by substitutions of specific bases. The simulations were conducted for free RNA and in complex with paromomycin. We found that the specific mutations affect the shape and dynamics of the binding cleft as well as significantly alter its electrostatic properties. The most pronounced changes were observed in the U1406C∶U1495A mutant, where important hydrogen bonds between the RNA and paromomycin were disrupted. The present study aims to clarify the underlying physicochemical mechanisms of bacterial resistance to aminoglycosides due to target mutations

Foot posture in people with medial compartment knee osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Foot posture has long been considered to contribute to the development of lower limb musculoskeletal conditions as it may alter the mechanical alignment and dynamic function of the lower limb. This study compared foot posture in people with and without medial compartment knee osteoarthritis (OA) using a range of clinical foot measures. The reliability of the foot measures was also assessed.</p> <p>Methods</p> <p>The foot posture of 32 patients with clinically and radiographically-confirmed OA predominantly in the medial compartment of the knee and 28 asymptomatic age-matched healthy controls was investigated using the foot posture index (FPI), vertical navicular height and drop, and the arch index. Independent t tests and effect size (Cohen's d) were used to investigate the differences between the groups in the foot posture measurements.</p> <p>Results</p> <p>Significant differences were found between the control and the knee OA groups in relation to the FPI (1.35 ± 1.43 vs. 2.46 ± 2.18, p = 0.02; <it>d </it>= 0.61, medium effect size), navicular drop (0.02 ± 0.01 vs. 0.03 ± 0.01, p = 0.01; <it>d </it>= 1.02, large effect size) and the arch index (0.22 ± 0.04 vs. 0.26 ± 0.04, p = 0.04; <it>d </it>= 1.02, large effect size). No significant difference was found for vertical navicular height (0.24 ± 0.03 vs. 0.23 ± 0.03, p = 0.54; <it>d </it>= 0.04, negligible effect size).</p> <p>Conclusion</p> <p>People with medial compartment knee OA exhibit a more pronated foot type compared to controls. It is therefore recommended that the assessment of patients with knee OA in clinical practice should include simple foot measures, and that the potential influence of foot structure and function on the efficacy of foot orthoses in the management of medial compartment knee OA be further investigated.</p

Daily Physical Activities and Sports in Adult Survivors of Childhood Cancer and Healthy Controls: A Population-Based Questionnaire Survey

BACKGROUND: Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. METHODOLOGY/PRINCIPAL FINDINGS: The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976-2003 at age 0-15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5 years and reached adulthood (≥20 years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35 years: 1.5, 95CI 1.2-2.0), female gender (OR 1.6, 95CI 1.3-1.9), French/Italian Speaking (OR 1.4, 95CI 1.1-1.7), and higher education (OR for university education: 2.0, 95CI 1.5-2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1-1.6), older age (OR for ≥35 years: 1.4, 95CI 1.1-1.8), migration background (OR 1.5, 95CI 1.3-1.8), French/Italian speaking (OR 1.4, 95CI 1.2-1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2-2.2), being married (OR 1.7, 95CI 1.5-2.0), having children (OR 1.3, 95CI 1.4-1.9), obesity (OR 2.4, 95CI 1.7-3.3), and smoking (OR 1.7, 95CI 1.5-2.1). Type of diagnosis was only associated with sports. CONCLUSIONS/SIGNIFICANCE: Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population