Biomedical subjects
Publications and source records attributed to Yael Paran.
In this report we discuss a patient with predominant right heart failure and pulmonary hypertension, caused by thyrotoxicosis due to Graves disease, which deteriorated to asystole, due to amiodarone administration for rapid atrial fibrillation.
Large-scale microscopy-based screens offer compelling advantages for assessing the effects of genetic and pharmacological modulations on a wide variety of cellular features. However, development of such assays is often confronted by an apparent conflict between the need for high throughput, which usually provides limited information on a large number of samples, and a high-content approach, providing detailed information on each sample. This chapter describes a novel high-resolution screening (HRS) platform that is able to acquire large sets of data at a high rate and light microscope resolution using specific "reporter cells," cultured in multiwell plates. To harvest extensive morphological and molecular information in these automated screens, we have constructed a general analysis pipeline that is capable of assigning scores to multiparameter-based comparisons between treated cells and controls. This chapter demonstrates the structure of this system and its application for several research projects, including screening of chemical compound libraries for their effect on cell adhesion, discovery of novel cytoskeletal genes, discovery of cell migration-related genes, and a siRNA screen for perturbation of cell adhesion.
AIMS: We reviewed all the publications concerning methadone-associated Torsades de Pointes (TdP) (polymorphic ventricular tachycardia) in opioid-dependent patients in order to characterize the clinical circumstances leading to this serious complication. METHODS: Our literature search yielded 14 reports on 40 patients with methadone-associated TdP. We gathered and recorded the risk factors for TdP mentioned in those reports, among other clinical aspects. RESULTS: The most prevalent risk factors for TdP were high-dose methadone (n = 39, 97.5%) and concomitant use of agents that increase serum methadone levels or trigger TdP (n = 22, 55%). HIV infection (n = 16), hypokalaemia (n = 14), female sex (n = 13), liver cirrhosis or renal failure (n = 11) and heart disease (n = 9) were also described. All the patients had at least one and 34 (85%) had two or more risk factors for TdP during methadone treatment. CONCLUSIONS: We wish to raise the level of awareness of risk factors for TdP among physicians in heroin-treatment clinics who frequently prescribe methadone.
The parameters that characterize the intricate water diffusion in tumors may serve to reveal their distinct pathology. Specifically, the application of diffusion magnetic resonance imaging (MRI) can aid in characterizing breast cancer, as well as monitoring response to therapy. We present here a non-invasive, quantitative MRI investigation, at high spatial resolution, of water diffusion in hormonal dependent MCF7 breast tumors implanted orthotopically in immunodeficient mice. Distinctive MRI protocols were designed in this study, utilizing a broad range of diffusion times and diffusion gradient strengths. Application of these protocols allowed water diffusion in the tissue extracellular and intracellular compartments to be distinguished, and the effect of restricted diffusion and water exchange on the water diffusion in these compartments to be evaluated. Pixel-by-pixel analysis yielded parametric maps of the estimated volume fraction and apparent diffusion coefficient of each compartment. The diffusion of the water in the extracellular microenvironment was approximately two fold slower than that of free water, and in the intracellular compartment was about one order of magnitude slower than that of free water and demonstrated restriction of water diffusion at long diffusion times. Mapping of the water fraction in each compartment was further employed to monitor changes during tumor progression and to assess tumor response to hormonal manipulation with a new antiestrogenic drug, tamoxifen methiodide (TMI). It was found that, in parallel to the growth arrest by this drug, the volume fraction of the slowly diffusing water increased, suggesting a TMI-induced cell swelling. This study can serve as a basis for extending diffusion breast MRI in the clinical setting.