114 research outputs found

    Inflammatory fibroid polyp of the ileum presenting with small bowel obstruction in an adult patient: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Inflammatory fibroid polyps are rare benign tumors of the gastrointestinal tract with the gastric antrum being the most common site, followed by the ileum. Histogenesis is still unknown and controversial. Inflammatory fibroid polyps are one of the rare benign conditions leading to intestinal obstruction in adults.</p> <p>Case presentation</p> <p>A 54-year-old Caucasian man presented with acute abdomen pain and a two month history of intermittent cramping and lower abdominal pain. Computed tomography imaging demonstrated a partial intestinal obstruction in the location of the terminal ileum. An ileo-ileal intussusception due to a mass lesion 15 cm proximal to the caecum was found on exploratory laparotomy. Intussusception was spontaneously reduced during exploration and a wedge resection was performed to the affected bowel segment. Histopathologic examination showed the mass to be an inflammatory fibroid polyp.</p> <p>Conclusion</p> <p>Although inflammatory fibroid polyps are rare and benign, in the case of intestinal obstruction the only solution is a surgical approach.</p

    Modular reorganization of the global network of gene regulatory interactions during perinatal human brain development.

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    BACKGROUND During early development of the nervous system, gene expression patterns are known to vary widely depending on the specific developmental trajectories of different structures. Observable changes in gene expression profiles throughout development are determined by an underlying network of precise regulatory interactions between individual genes. Elucidating the organizing principles that shape this gene regulatory network is one of the central goals of developmental biology. Whether the developmental programme is the result of a dynamic driven by a fixed architecture of regulatory interactions, or alternatively, the result of waves of regulatory reorganization is not known. RESULTS Here we contrast these two alternative models by examining existing expression data derived from the developing human brain in prenatal and postnatal stages. We reveal a sharp change in gene expression profiles at birth across brain areas. This sharp division between foetal and postnatal profiles is not the result of pronounced changes in level of expression of existing gene networks. Instead we demonstrate that the perinatal transition is marked by the widespread regulatory rearrangement within and across existing gene clusters, leading to the emergence of new functional groups. This rearrangement is itself organized into discrete blocks of genes, each targeted by a distinct set of transcriptional regulators and associated to specific biological functions. CONCLUSIONS Our results provide evidence of an acute modular reorganization of the regulatory architecture of the brain transcriptome occurring at birth, reflecting the reassembly of new functional associations required for the normal transition from prenatal to postnatal brain development

    Compound double ileoileal and ileocecocolic intussusception caused by lipoma of the ileum in an adult patient: A case report

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    <p>Abstract</p> <p>Introduction</p> <p>The initial diagnosis of intussusception in adults very often can be missed and cause delayed treatment and possible serious complications. We report the case of an adult patient with complicated double ileoileal and ileocecocolic intussusception.</p> <p>Case presentation</p> <p>A 46-year-old Caucasian man was transferred from the gastroenterology service to the abdominal surgery service with severe abdominal pain, nausea, and vomiting. An abdominal ultrasound, barium enema, and abdominal computed tomography scan revealed an intraluminal obstruction of his ascending colon. Plain abdominal X-rays showed diffuse air-fluid levels in his small intestine. A double ileoileal and ileocecocolic intussusception was found during an emergent laparotomy. A right hemicolectomy, including resection of a long segment of his ileum, was performed. The postoperative period was complicated by acute renal failure, shock liver, and pulmonary thromboembolism. Our patient was discharged from the hospital after 30 days. An anatomical pathology examination revealed a lipoma of his ileum.</p> <p>Conclusions</p> <p>Intussusception in adults requires early surgical resection regardless of the nature of the initial cause. Delayed treatment can cause very serious complications.</p

    Global Considerations in Hierarchical Clustering Reveal Meaningful Patterns in Data

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    BACKGROUND: A hierarchy, characterized by tree-like relationships, is a natural method of organizing data in various domains. When considering an unsupervised machine learning routine, such as clustering, a bottom-up hierarchical (BU, agglomerative) algorithm is used as a default and is often the only method applied. METHODOLOGY/PRINCIPAL FINDINGS: We show that hierarchical clustering that involve global considerations, such as top-down (TD, divisive), or glocal (global-local) algorithms are better suited to reveal meaningful patterns in the data. This is demonstrated, by testing the correspondence between the results of several algorithms (TD, glocal and BU) and the correct annotations provided by experts. The correspondence was tested in multiple domains including gene expression experiments, stock trade records and functional protein families. The performance of each of the algorithms is evaluated by statistical criteria that are assigned to clusters (nodes of the hierarchy tree) based on expert-labeled data. Whereas TD algorithms perform better on global patterns, BU algorithms perform well and are advantageous when finer granularity of the data is sought. In addition, a novel TD algorithm that is based on genuine density of the data points is presented and is shown to outperform other divisive and agglomerative methods. Application of the algorithm to more than 500 protein sequences belonging to ion-channels illustrates the potential of the method for inferring overlooked functional annotations. ClustTree, a graphical Matlab toolbox for applying various hierarchical clustering algorithms and testing their quality is made available. CONCLUSIONS: Although currently rarely used, global approaches, in particular, TD or glocal algorithms, should be considered in the exploratory process of clustering. In general, applying unsupervised clustering methods can leverage the quality of manually-created mapping of proteins families. As demonstrated, it can also provide insights in erroneous and missed annotations

    Genomic Phenotyping by Barcode Sequencing Broadly Distinguishes between Alkylating Agents, Oxidizing Agents, and Non-Genotoxic Agents, and Reveals a Role for Aromatic Amino Acids in Cellular Recovery after Quinone Exposure

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    Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic ‘barcode’, were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput ‘barcode’ sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.Unilever (Firm)National Cancer Institute (U.S.) (R01-CA055042 (now R01-ES022872))Massachusetts Institute of Technology. Center for Environmental Health Sciences (Grant NIEHS P30-ES002109

    Analysis of circulating hem-endothelial marker RNA levels in preterm infants

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    <p>Abstract</p> <p>Background</p> <p>Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications.</p> <p>Methods</p> <p>Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30). Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (<it>AC133, Tie-2, Flk-1 (VEGFR2) and Scl/Tal1</it>) in association with characteristics of prematurity and preterm morbidity.</p> <p>Results</p> <p>Circulating <it>Tie-2 </it>and <it>SCL/Tal1 </it>RNA levels displayed an inverse correlation to gestational age (GA). We observed significantly elevated <it>Tie-2 </it>levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations.</p> <p>Conclusion</p> <p>These preliminary findings suggest that circulating RNA levels especially <it>Tie2 </it>and <it>SCL </it>decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.</p

    In Silico Ascription of Gene Expression Differences to Tumor and Stromal Cells in a Model to Study Impact on Breast Cancer Outcome

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    Breast tumors consist of several different tissue components. Despite the heterogeneity, most gene expression analyses have traditionally been performed without prior microdissection of the tissue sample. Thus, the gene expression profiles obtained reflect the mRNA contribution from the various tissue components. We utilized histopathological estimations of area fractions of tumor and stromal tissue components in 198 fresh-frozen breast tumor tissue samples for a cell type-associated gene expression analysis associated with distant metastasis. Sets of differentially expressed gene-probes were identified in tumors from patients who developed distant metastasis compared with those who did not, by weighing the contribution from each tumor with the relative content of stromal and tumor epithelial cells in their individual tumor specimen. The analyses were performed under various assumptions of mRNA transcription level from tumor epithelial cells compared with stromal cells. A set of 30 differentially expressed gene-probes was ascribed solely to carcinoma cells. Furthermore, two sets of 38 and five differentially expressed gene-probes were mostly associated to tumor epithelial and stromal cells, respectively. Finally, a set of 26 differentially expressed gene-probes was identified independently of cell type focus. The differentially expressed genes were validated in independent gene expression data from a set of laser capture microdissected invasive ductal carcinomas. We present a method for identifying and ascribing differentially expressed genes to tumor epithelial and/or stromal cells, by utilizing pathologic information and weighted t-statistics. Although a transcriptional contribution from the stromal cell fraction is detectable in microarray experiments performed on bulk tumor, the gene expression differences between the distant metastasis and no distant metastasis group were mostly ascribed to the tumor epithelial cells of the primary breast tumors. However, the gene PIP5K2A was found significantly elevated in stroma cells in distant metastasis group, compared to stroma in no distant metastasis group. These findings were confirmed in gene expression data from the representative compartments from microdissected breast tissue. The method described was also found to be robust to different histopathological procedures

    Bar-Coded Pyrosequencing Reveals the Responses of PBDE-Degrading Microbial Communities to Electron Donor Amendments

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    Polybrominated diphenyl ethers (PBDEs) can be reductively degraded by microorganisms under anaerobic conditions. However, little is known about the effect of electron donors on microbial communities involved in PBDEs degradation. Here we employed 454 Titanium pyrosequencing to examine the phylogenetic diversity, composition, structure and dynamics of microbial communities from microcosms under the conditions of different electron donor amendments. The community structures in each of the five alternate electron donor enrichments were significantly shifted in comparison with those of the control microcosm. Commonly existing OTUs between the treatment and control consortia increased from 5 to 17 and more than 50% of OTUs increased around 13.7 to 186 times at least in one of the microcosms after 90-days enrichment. Although the microbial communities at different taxonomic levels were significantly changed by different environmental variable groups in redundancy analysis, significant correlations were observed between the microbial communities and PBDE congener profiles. The lesser-brominated PBDE congeners, tri-BDE congener (BDE-32) and hexa-BDE, were identified as the key factors shaping the microbial community structures at OTU level. Some rare populations, including the known dechlorinating bacterium, Dehalobacter, showed significant positive-correlation with the amounts of PBDE congeners in the consortia. The same results were also observed on some unclassified bacteria. These results suggest that PBDEs-degrading microbial communities can be successfully enriched, and their structures and compositions can be manipulated through adjusting the environmental parameters
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