Interleukin-13 selectively suppresses the growth of human macrophage progenitors at the late stage

Interleukin-13 (IL-13) is a pleiotropic cytokine that inhibits the production of inflammatory cytokines of monocytes. We investigated the effects of IL-13 on the clonal growth of human hematopoietic progenitors. IL-13 alone did not support any colony formation. IL-13 markedly suppressed macrophage colonies that were formed in the presence of IL-3 and erythropoietin, granulocyte-macrophage colony- stimulating factor, or macrophage colony-stimulating factor. Macrophage colony cells showed dendritic cell-line morphology and cellular aggregates. IL-13 did not affect granulocyte colony and erythroid burst formation. Delayed addition of IL-13 and replating onto the culture dishes with IL-13 showed that macrophage colony formation was suppressed during days 8 and 14 of culture. These results indicate that IL-13 affects the growth of the late stage of committed macrophage progenitors. Single-cell culture of isolated CD34+CD33+ cells with IL- 13 confirmed that macrophage colony formation was significantly suppressed. These results show that IL-13 directly suppresses the proliferation of differentiating macrophages. In addition, these suppressive effects of IL-13 were synergistic with IL-4. Furthermore, in the liquid culture of bone marrow cells in the presence of IL-13, the number of CD14 (monocyte-macrophage antigen)-positive cells decreased and CD18 (LFA-1 beta)-positive cells increased. It is concluded that IL-13 affects the growth of the late stage of macrophage precursors as well as mature monocytes. Induction of differentiation of human monocytes may be correlated with the suppression of their progenitors.     

Using the wisdom of the crowds to find critical errors in biomedical ontologies: a study of SNOMED CT

Objectives The verification of biomedical ontologies is an arduous process that typically involves peer review by subject-matter experts. This work evaluated the ability of crowdsourcing methods to detect errors in SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to address the challenges of scalable ontology verification.Methods We developed a methodology to crowdsource ontology verification that uses micro-tasking combined with a Bayesian classifier. We then conducted a prospective study in which both the crowd and domain experts verified a subset of SNOMED CT comprising 200 taxonomic relationships.Results The crowd identified errors as well as any single expert at about one-quarter of the cost. The inter-rater agreement (κ) between the crowd and the experts was 0.58; the inter-rater agreement between experts themselves was 0.59, suggesting that the crowd is nearly indistinguishable from any one expert. Furthermore, the crowd identified 39 previously undiscovered, critical errors in SNOMED CT (eg, ‘septic shock is a soft-tissue infection’).Discussion The results show that the crowd can indeed identify errors in SNOMED CT that experts also find, and the results suggest that our method will likely perform well on similar ontologies. The crowd may be particularly useful in situations where an expert is unavailable, budget is limited, or an ontology is too large for manual error checking. Finally, our results suggest that the online anonymous crowd could successfully complete other domain-specific tasks.Conclusions We have demonstrated that the crowd can address the challenges of scalable ontology verification, completing not only intuitive, common-sense tasks, but also expert-level, knowledge-intensive tasks.     

The role of radiotherapy in the management of primary cutaneous neuroendocrine tumors (Merkel cell or trabecular carcinoma): experience at the Peter MacCallum Cancer Institute (Melbourne, Australia)

Clinical presentation, treatment, and radiation response data are presented for 20 patients with primary cutaneous neuroendocrine tumors (Merkel cell or trabecular carcinoma). Thirty-six sites were irradiated, 26 sites were local recurrences after surgery or metastases, only 3 primary tumors were irradiated de novo. In 22 out of 23 sites (96%) a complete response of measurable tumor was observed and 1 partial response (4%), an overall response rate of 100%. Thirteen sites were irradiated prophylactically with no measurable disease present and no recurrences have been seen in these areas. There was only 1 recurrence in an irradiated site (after a low radiation dose). Forty percent (8/20) either had distant metastases at presentation (5 patients) or developed them after radiotherapy (3 patients) and five of these patients have died of metastatic disease. Follow-up time ranged from 1-77 months, and actuarial 5-year survival was 63%. In view of these findings we would advocate the wider study of primary radiotherapy after biopsy or excision biopsy for the primary lesion, and prophylactic nodal irradiation with the object of avoiding extensive surgery in these often elderly patients.     

Parental health attitudes, illnesses and supports and the referral of children to medical specialists

Parental illness and maternal health beliefs in the parents of a group of 40 children referred to a paediatric neurology service because of headaches were compared with illness histories and health beliefs in the parents of a matched group of 40 children presenting to the same service with recognized structural pathology, mainly epilepsy. The study focused on the mother's perceptions of her own health (current and past), on life events, social supports and on her beliefs about her own health and the validity of medical reassurance. Significant differences between the two groups were found in relation to: (a) the greater amount of illness experienced by both parents in the index group (i.e. parents of children with headaches), particularly the mothers, both as children and as adults; (b) the greater amount of illness present in the families of the index group in the 3 years prior to being seen by the neurologist; (c) the greater number of index mothers who had experienced the loss of their own mothers caused by death; (d) the greater tendency of the index mothers to express feelings of loneliness; (e) the greater proportion of index mothers who, in response to the Whiteley Attitudes to Health Questionnaire, expressed both (i) concern about serious disease in themselves, and (ii) reluctance to accept medical reassurance; (f) on the other hand, significantly more'comparison mothers'complained of currently suffering'many different symptoms'.     

Familial aplasia of the inferior rectus muscles

PURPOSE: We describe inferior rectus aplasia in three members of a family. No family member showed signs of craniofacial dysostosis syndromes or neurofibromatosis. PATIENTS AND FINDINGS: A woman with abnormal head posture, right exotropia, and right hypotropia presented to our clinic. She mentioned that her two children had similar problems. A provisional diagnosis of ocular fibrosis or atypical Duane syndrome was made and she underwent surgery. During surgery, the inferior rectus muscle could not be identified in either eye. Subsequently, her children were examined and orbital magnetic resonance imaging (MRI) was performed for all family members. MRI confirmed bilateral absence of the inferior rectus muscles in the mother and unilateral absence with atrophic and fibrotic contralateral inferior rectus muscles in the children. CONCLUSION: This is the first report in the literature of a family with aplastic inferior rectus muscles with no signs of craniosynostosis or neurofibromatosis.     

The effect of human antiendotoxin monoclonal antibodies on endotoxin-induced lung injury in the rat

A model of endotoxin-induced lung injury was developed in the rat. We found that 24 h after intravenously administered endotoxin (3 mg/kg) there was increased clearance of the isotope 99mTcDTPA from the lung to blood, increased neutrophils in the lung in bronchoalveolar lavage, and increased levels of products of peroxidation of lipids and nucleic acid in the serum. Using this model, we evaluated the effect of pretreatment of rats with a human monoclonal antibody specific to the core glycolipid that is common to all endotoxins. We found that pretreatment prevented the increased clearance of 99mTcDTPA from the lung, as well as the increase in lipid peroxidation products in the serum. The antibody did not prevent increased neutrophil accumulation in the lung. The findings suggest that the administration of human antiendotoxin monoclonal antibodies prior to endotoxemia may prevent some of the changes in the lung associated with endotoxin.     

Design and characterization of synthetic fungal-bacterial consortia for direct production of isobutanol from cellulosic biomass

Synergistic microbial communities are ubiquitous in nature and exhibit appealing features, such as sophisticated metabolic capabilities and robustness. This has inspired fast-growing interest in engineering synthetic microbial consortia for biotechnology development. However, there are relatively few reports of their use in real-world applications, and achieving population stability and regulation has proven to be challenging. In this work, we bridge ecology theory with engineering principles to develop robust synthetic fungal-bacterial consortia for efficient biosynthesis of valuable products from lignocellulosic feedstocks. The required biological functions are divided between two specialists: the fungus Trichoderma reesei, which secretes cellulase enzymes to hydrolyze lignocellulosic biomass into soluble saccharides, and the bacterium Escherichia coli, which metabolizes soluble saccharides into desired products. We developed and experimentally validated a comprehensive mathematical model for T. reesei/E. coli consortia, providing insights on key determinants of the system’s performance. To illustrate the bioprocessing potential of this consortium, we demonstrate direct conversion of microcrystalline cellulose and pretreated corn stover to isobutanol. Without costly nutrient supplementation, we achieved titers up to 1.88 g/L and yields up to 62% of theoretical maximum. In addition, we show that cooperator–cheater dynamics within T. reesei/E. coli consortia lead to stable population equilibria and provide a mechanism for tuning composition. Although we offer isobutanol production as a proof-of-concept application, our modular system could be readily adapted for production of many other valuable biochemicals.     

cDNA recombinant plasmid complementary to mRNAs for light chains 1 and 3 of mouse skeletal muscle myosin.

A recombinant plasmid with a cDNA sequence transcribed from mouse skeletal muscle RNA is shown to hybridize with mRNAs for myosin light chains LC1F and LC3F. The inserted fragment corresponds exclusively to the 3'-noncoding region of the mRNA. It hybridizes almost exclusively with the two light chain messengers from fast skeletal muscle RNA of adult mouse. Slight hybridization is seen with RNA from heart muscle and embryonic skeletal muscle. The implications of the conservation of the 3'-noncoding regions between the two mRNAs are discussed.