Clonal chromosome aberrations in Philadelphia-negative cells from chronic myelocytic leukemia patients treated with imatinib mesylate: report of two cases

Imatinib mesylate (tested as STI571), an abl kinase inhibitor, induces sustained, complete hematologic and cytogenetic responses in chronic myelocytic leukemia (CML) patients; however, emergence of clonal chromosomal aberrations in Philadelphia-negative (Ph-) cells during treatment has been reported. We describe two CML patients in chronic phase who presented with complete cytogenetic responses during imatinib mesylate therapy but developed new clonal chromosomal rearrangements in Ph- cells. The first patient presented with a duplication of chromosome 1, dup(1)(q21q42), and the second showed two new clonal aberrations consisting of inv(1)(q12q32) and del(7)(q22) in the same clone.     

Innovations in curriculum design: A multi-disciplinary approach to teaching statistics to undergraduate medical students

Background  

Statistics is relevant to students and practitioners in medicine and health sciences and is increasingly taught as part of the medical curriculum. However, it is common for students to dislike and under-perform in statistics. We sought to address these issues by redesigning the way that statistics is taught.     

DicomWorks: Software for Reviewing DICOM Studies and Promoting Low-cost Teleradiology

DicomWorks is freeware software for reading and working on medical images [digital imaging and communication in medicine (DICOM)]. It was jointly developed by two research laboratories, with the feedback of more than 35,000 registered users throughout the world who provided information to guide its development. We detail their occupations (50% radiologists, 20% engineers, 9% medical physicists, 7% cardiologists, 6% neurologists, and 8% others), geographic origins, and main interests in the software. The viewer’s interface is similar to that of a picture archiving and communication system viewing station. It provides basic but efficient tools for opening DICOM images and reviewing and exporting them to teaching files or digital presentations. E-mail, FTP, or DICOM protocols are supported for transmitting images through a local network or the Internet. Thanks to its wide compatibility, a localized (15 languages) and user-friendly interface, and its opened architecture, DicomWorks helps quick development of non proprietary, low-cost image review or teleradiology solutions in developed and emerging countries.     

Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation

During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior–posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3^−/− embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.     

Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

Background  

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1β is primarily neurotoxic in ischemic stroke, TNF-α may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1β and TNF-α are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice.     

Shuttle vectors for <Emphasis Type="Italic">Candida albicans</Emphasis>: control of plasmid copy number and elevated expression of cloned genes

Plasmids containing the inosine monophosphate dehydrogenase gene CaIMH3 from Candida albicans strain ATCC 32354 transform their host to resistance against mycophenolic acid (MPA). The transformants maintain the plasmids at a high copy number (20–40 per cell) and express the CaIMH3 gene at very high levels relative to untransformed controls. The plasmid copy number can be controlled by the concentration of MPA in the media. The transformation procedure is reproducible and the efficiency of transformation is high, up to 15,000 per microgram. Unrearranged plasmids are readily recovered by transforming total DNA from transformants back into Escherichia coli. C. albicans genes cloned into the plasmid are expressed at elevated levels relative to untransformed controls. A derivative vector containing the CaMAL2 promoter and termination sequences expresses the CaERG11 ORF at high levels and confers moderate resistance to fluconazole. These shuttle vectors should facilitate global genomics approaches in C. albicans that have been hampered by its diploid genome.     

High-throughput genetic screening using matrix-assisted laser desorption/ionization mass spectrometry

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become a powerful and widespread analytical tool in all fields of life science. Compared with other techniques, its high accuracy and sensitivity makes it a superior method, especially for the analysis of nucleic acids. Recent problems in the analysis of nucleic acids by MALDI-TOF MS can be solved using an automated MALDI-compatible sample-preparation system. Together with the reliable minisequencing assay, high-throughput genotyping of single nucleotide polymorphisms by MALDI-TOF MS is able to become a routine method in research, clinical genetics and diagnostics.     

Functional Cluster Analysis of CT Perfusion Maps: A New Tool for Diagnosis of Acute Stroke?

CT perfusion imaging constitutes an important contribution to the early diagnosis of acute stroke. Cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) maps are used to estimate the severity of cerebral damage after acute ischemia. We introduce functional cluster analysis as a new tool to evaluate CT perfusion in order to identify normal brain, ischemic tissue and large vessels. CBF, CBV and TTP maps represent the basis for cluster analysis applying a partitioning (k-means) and density-based (density-based spatial clustering of applications with noise, DBSCAN) paradigm. In patients with transient ischemic attack and stroke, cluster analysis identified brain areas with distinct hemodynamic properties (gray and white matter) and segmented territorial ischemia. CBF, CBV and TTP values of each detected cluster were displayed. Our preliminary results indicate that functional cluster analysis of CT perfusion maps may become a helpful tool for the interpretation of perfusion maps and provide a rapid means for the segmentation of ischemic tissue.     

Developing resources to teach and assess the core competencies: a collaborative approach.

Graduate medical education programs face new challenges as they seek to comply with the mandate from the Accreditation Council on Graduate Medical Education to demonstrate that they are teaching and assessing residents on the six core competencies. The authors describe a project designed as a collaborative venture between the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the Center for Educational Outcomes at Dartmouth College (CEdO) to provide residency programs in allergy/immunology with resources for teaching and assessing the core competencies. The goal was to create a set of learning and assessment resources that maximized the content knowledge expertise provided by the AAAAI and the learning expertise provided by CEdO. A highly interactive, iterative process was used to create a set of Web-based modules. Bilateral communication, buy-in, and active involvement in the process were seen as crucial to the development of resources and their successful implementation. Approximately 18 months after the modules were made available to training program directors, 80% of the directors surveyed were aware of and had accessed the modules. The joint creation process used in this project, designed to be generally applicable across specialties, reveals how the burden of meeting new requirements can be decreased when experts in content knowledge and experts in learning collaborate.     

The Effects of Perceived Stress on Reactions to Messages Designed to Increase Health Behaviors

This study examined the impact of perceived stress on responses to messages that encouraged the performance of health promotion and disease detection behaviors. It was hypothesized that increases in perceived stress would be associated with decreased processing of messages encouraging disease detection behaviors, and that increases in perceived stress would not effect the processing of messages encouraging health promotion behaviors. To test these hypotheses participants completed a perceived stress measure and then read a message that encouraged the performance of either a health promotion or a disease detection behavior. Then the participants were asked to indicate their agreement with the message and to attempt to recall the message. The results indicated that participants experiencing higher levels of perceived stress spent less time reading and recalled less of the messages about detection behaviors than of the messages about promotion behaviors. When participants were experiencing lower levels of perceived stress these differences disappeared.

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