A Study of Sum Peak Method in Biological Substances by Using 111In

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Temporal and sequential changes of glial cells and cytokine expression during neuronal degeneration after transient global ischemia in rats

<p>Abstract</p> <p>Background</p> <p>How glial cells and cytokines are associated with the progression of delayed neuronal death induced by transient global ischemia is still unclear. To further clarify this point, we studied morphological changes in glial cells (microglial cells and astrocytes), and cytokine protein levels, during the progression of neuronal cell loss in CA1 (Cornu Ammonis 1) of the hippocampus after transient global ischemia.</p> <p>Methods</p> <p>Morphological changes in glial cells were studied immuno-histochemically. Nine cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ and TNF-α) were simultaneously measured by a multiplexed bead-based immunoassay from 6 h to day21 after transient four vessel occlusion (4VO) in rats.</p> <p>Results</p> <p>During the process of neuronal loss, we observed four distinct phases: (1) lag phase day0-2 (no NeuN+ cell loss observed), (2) exponential phase day2-7 (NeuN+ cells reduced in number exponentially), (3) deceleration phase day7-14 (reduction rate of NeuN+ cells became low), (4) stationary phase day14 onward (NeuN+ cell loss progressed no longer). In the lag phase, activated glial cells were observed in the entire hippocampus but later were gradually restricted to CA1. Cytokine protein levels in the lag and exponential phases were lower than in the deceleration and stationary phases. IL-1α, IL-1β, IL-4, IL-6 and IFN-γ in 4VO were significantly higher in all four phases than in sham. Compared with sham level, GM-CSF was significantly high in the deceleration phase. TNF-α was significantly high in both the deceleration and stationary phases.</p> <p>Conclusion</p> <p>Ischemic stress in 4VO activated glial cells in areas beyond CA1 in the lag phase. Pyramidal neurons were injured in CA1 from the end of the lag phase and then neuronal cells reduced in CA1 in the exponential phase. After neuronal death began, the influence of dead cells on glial cells and cytokine expression gradually became stronger than the influence by ischemic stress. Therefore, from the deceleration phase, changes in glial cells and cytokine production were likely caused by dead cells. Cytokine interaction in the microenvironment may determine the functions of IL-1α, IL-1β, IL-4, IL-6 and IFN-γ in all four phases. The function of GM-CSF and TNF-α in the deceleration phase may be neurotrophic.</p

Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2

SummaryMicroRNAs (miRNAs) are genomically encoded small RNAs used by organisms to regulate the expression of proteins generated from messenger RNA transcripts. The in vivo requirement of specific miRNAs in mammals through targeted deletion remains unknown, and reliable prediction of mRNA targets is still problematic. Here, we show that miRNA biogenesis in the mouse heart is essential for cardiogenesis. Furthermore, targeted deletion of the muscle-specific miRNA, miR-1-2, revealed numerous functions in the heart, including regulation of cardiac morphogenesis, electrical conduction, and cell-cycle control. Analyses of miR-1 complementary sequences in mRNAs upregulated upon miR-1-2 deletion revealed an enrichment of miR-1 “seed matches” and a strong tendency for potential miR-1 binding sites to be located in physically accessible regions. These findings indicate that subtle alteration of miRNA dosage can have profound consequences in mammals and demonstrate the utility of mammalian loss-of-function models in revealing physiologic miRNA targets

Calcified amorphous tumor of the heart in an adult female: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cardiac calcified amorphous tumor is a rare, non-neoplastic intra-cavity cardiac mass composed of calcium deposits in a background of amorphous degenerating fibrinous material. Only a few cases of this rare lesion have been reported in the available literature. Clinico-pathological differentiation of this lesion from calcified atrial myxoma, calcified thrombi or other cardiac neoplasms is extremely difficult; hence pathologic examination is the mainstay of diagnosis. To the best of our knowledge this entity has not been reported in the Indian literature.</p> <p>Case presentation</p> <p>A 40-year-old woman of Indian origin presented with progressive dyspnea, fatigue and cough. She was diagnosed as having a calcified right atrial mass. The mass was excised. Histologic examination revealed the mass to be composed of amorphous eosinophilic fibrin with dense calcification. No myxomatous tissue was seen and a final diagnosis of calcified amorphous tumor of the heart was rendered.</p> <p>Conclusions</p> <p>Calcified amorphous tumor is a rare cardiac lesion with an excellent outcome following complete surgical removal. Since clinico-radiologic differentiation from other cardiac masses is not possible in most cases, histopathological examination is the only modality for diagnosis. Hence, histopathologists should be aware of this rare entity in the differential diagnoses of cardiac mass.</p

Virtual slides in peer reviewed, open access medical publication

<p>Abstract</p> <p>Background</p> <p>Application of virtual slides (VS), the digitalization of complete glass slides, is in its infancy to be implemented in routine diagnostic surgical pathology and to issues that are related to tissue-based diagnosis, such as education and scientific publication.</p> <p>Approach</p> <p>Electronic publication in Pathology offers new features of scientific communication in pathology that cannot be obtained by conventional paper based journals. Most of these features are based upon completely open or partly directed interaction between the reader and the system that distributes the article. One of these interactions can be applied to microscopic images allowing the reader to navigate and magnify the presented images. VS and interactive Virtual Microscopy (VM) are a tool to increase the scientific value of microscopic images.</p> <p>Technology and Performance</p> <p>The open access journal Diagnostic Pathology <url>http://www.diagnosticpathology.org</url> has existed for about five years. It is a peer reviewed journal that publishes all types of scientific contributions, including original scientific work, case reports and review articles. In addition to digitized still images the authors of appropriate articles are requested to submit the underlying glass slides to an institution (DiagnomX.eu, and Leica.com) for digitalization and documentation. The images are stored in a separate image data bank which is adequately linked to the article. The normal review process is not involved. Both processes (peer review and VS acquisition) are performed contemporaneously in order to minimize a potential publication delay. VS are not provided with a DOI index (digital object identifier). The first articles that include VS were published in March 2011.</p> <p>Results and Perspectives</p> <p>Several logistic constraints had to be overcome until the first articles including VS could be published. Step by step an automated acquisition and distribution system had to be implemented to the corresponding article. The acceptance of VS by the reader is high as well as by the authors. Of specific value are the increased confidence to and reputation of authors as well as the presented information to the reader. Additional associated functions such as access to author-owned related image collections, reader-controlled automated image measurements and image transformations are in preparation.</p> <p>Virtual Slides</p> <p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/1232133347629819</url>.</p

Recode-2: new design, new search tools, and many more genes

'Recoding' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. Although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of &lsquo;recoded&rsquo; genes lags far behind annotation of 'standard' genes. In order to address this issue, provide a service to researchers in the field, and offer training data for developers of gene-annotation software, we have gathered together known cases of recoding within the Recode database. Recode-2 is an improved and updated version of the database. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. At present, the Recode-2 database stores information on approximately 1500 genes that are known to utilize recoding in their expression&mdash;a factor of approximately three increase over the previous version of the database. Recode-2 is available at http://recode.ucc.i

A new kinetic model reveals the synergistic effect of E-, P- and A-sites on +1 ribosomal frameshifting

Programmed ribosomal frameshifting (PRF) is a process by which ribosomes produce two different polypeptides from the same mRNA. In this study, we propose three different kinetic models of +1 PRF, incorporating the effects of the ribosomal E-, P- and A-sites toward promoting efficient +1 frameshifting in Escherichia coli. Specifically, the timing of E-site tRNA dissociation is discussed within the context of the kinetic proofreading mechanism of aminoacylated tRNA (aa-tRNA) selection. Mathematical modeling using previously determined kinetic rate constants reveals that destabilization of deacylated tRNA in the E-site, rearrangement of peptidyl-tRNA in the P-site, and availability of cognate aa-tRNA corresponding to the A-site act synergistically to promote efficient +1 PRF. The effect of E-site codon:anticodon interactions on +1 PRF was also experimentally examined with a dual fluorescence reporter construct. The combination of predictive modeling and empirical testing allowed the rate constant for P-site tRNA slippage (ks) to be estimated as ks ≈1.9 s−1 for the release factor 2 (RF2) frameshifting sequence. These analyses suggest that P-site tRNA slippage is the driving force for +1 ribosomal frameshifting while the presence of a ‘hungry codon’ in the A-site and destabilization in the E-site further enhance +1 PRF in E. coli

Quality of reporting internal and external validity data from randomized controlled trials evaluating stents for percutaneous coronary intervention

<p>Abstract</p> <p>Background</p> <p>Stents are commonly used to treat patients with coronary artery disease. However, the quality of reporting internal and external validity data in published reports of randomised controlled trials (RCTs) of stents has never been assessed.</p> <p>The objective of our study was to evaluate the quality of reporting internal and external validity data in published reports of RCTs assessing the stents for percutaneous coronary interventions.</p> <p>Methods</p> <p>A systematic literature review was conducted. Reports of RCTs assessing stents for percutaneous coronary interventions indexed in MEDLINE and the Cochrane Central Register of Controlled Trials and published between January 2003 and September 2008 were selected. A standardized abstraction form was used to extract data. All analyses were adjusted for the effect of clustering articles by journal.</p> <p>Results</p> <p>132 articles were analyzed. The generation of the allocation sequence was adequate in 58.3% of the reports; treatment allocation was concealed in 34.8%. Adequate blinding was reported in one-fifth of the reports. An intention-to-treat analysis was described in 79.5%. The main outcome was a surrogate angiographic endpoint in 47.0%. The volume of interventions per center was described in two reports. Operator expertise was described in five (3.8%) reports. The quality of reporting was better in journals with high impact factors and in journals endorsing the CONSORT statement.</p> <p>Conclusion</p> <p>The current reporting of results of RCTs testing stents needs to be improved to allow readers to appraise the risk of bias and the applicability of the results.</p

Heme Mediated STAT3 Activation in Severe Malaria

The mortality of severe malaria [cerebral malaria (CM), severe malaria anemia (SMA), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)] remains high despite the availability associated with adequate treatments. Recent studies in our laboratory and others have revealed a hitherto unknown correlation between chemokine CXCL10/CXCR3, Heme/HO-1 and STAT3 and cerebral malaria severity and mortality. Although Heme/HO-1 and CXCL10/CXCR3 interactions are directly involved in the pathogenesis of CM and fatal disease, the mechanism dictating how Heme/HO-1 and CXCL10/CXCR3 are expressed and regulated under these conditions is still unknown. We therefore tested the hypothesis that these factors share common signaling pathways and may be mutually regulated.We first clarified the roles of Heme/HO-1, CXCL10/CXCR3 and STAT3 in CM pathogenesis utilizing a well established experimental cerebral malaria mouse (ECM, P. berghei ANKA) model. Then, we further determined the mechanisms how STAT3 regulates HO-1 and CXCL10 as well as mutual regulation among them in CRL-2581, a murine endothelial cell line.The results demonstrate that (1) STAT3 is activated by P. berghei ANKA (PBA) infection in vivo and Heme in vitro. (2) Heme up-regulates HO-1 and CXCL10 production through STAT3 pathway, and regulates CXCL10 at the transcriptional level in vitro. (3) HO-1 transcription is positively regulated by CXCL10. (4) HO-1 regulates STAT3 signaling.Our data indicate that Heme/HO-1, CXCL10/CXCR3 and STAT3 molecules as well as related signaling pathways play very important roles in the pathogenesis of severe malaria. We conclude that these factors are mutually regulated and provide new opportunities to develop potential novel therapeutic targets that could be used to supplement traditional prophylactics and treatments for malaria and improve clinical outcomes while reducing malaria mortality. Our ultimate goal is to develop novel therapies targeting Heme or CXCL10-related biological signaling molecules associated with development of fatal malaria