552 research outputs found

    Correspondence from a UMaine Alumnus

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    Typewritten letter from Jon H. Towle expressing support for the Civil Rights of the members of the Wilde-Stein Club

    Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

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    BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

    Making sense of illness: the experiences of users of complementary medicine

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    The present study investigated the experiences of users of complementary and alternative medicine (CAM) using a qualitative approach. In-depth interviews were conducted with 11 frequent users and analysed using interpretative phenomenological analysis (IPA). Results indicated that the patient-practitioner relationship and explanatory frameworks provided by CAM were perceived as important components of the therapeutic process, irrespective of treatment efficacy. CAM served a variety of functions beyond the explicit relief of symptoms by increasing energy and relaxation, facilitating coping and enhancing self/other awareness. It is therefore important that these wider effects are taken into account when evaluating complementary medicine in order to accurately reflect patients' experiences

    Periapical lesions in hominids: Abscesses on the maxilla of a 2 million-year-old early Homo specimen

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    Periapical lesions can develop after exposure of a tooth's pulp chamber and are commonly associated with heavy crown wear, trauma, or caries. In this study, maxilla and mandible fragments from the South African fossil hominin collections were studied, including specimens assigned to Homo naledi, Paranthropus robustus, Australopithecus africanus, and early Homo. Gorilla gorilla gorilla, Pan troglodytes, and Homo sapiens were also studied for comparative purposes. Only one fossil hominin specimen displayed voids consistent with periapical lesions. The specimen, SK 847, is described as early Homo and has been dated to 2.3–1.65 Ma. There is one definite periapical lesion and likely more with post‐mortem damage, all on the anterior aspect of the maxilla and associated with the incisors. The lesions originate from the apices of the incisor roots and are therefore unlikely to represent a systemic disease such as multiple myeloma. The one well‐preserved lesion was likely an abscess rather than a cyst or granuloma, with a rounded thickened rim around the lesion. These lesions in an early Homo specimen highlight that this individual used their anterior dentition extensively, to the point that the pulp chambers were exposed on multiple teeth. This is one of the earliest hominin examples of periapical lesions and shows that this individual was able to cope with potentially several concurrent abscesses, clearly surviving for an extended period. Periapical lesions are relatively common in the great ape (P. troglodytes: 1.99%; G. gorilla gorilla: 1.86%) and human samples (2.50%) but absent in large samples of P. robustus and A. africanus (n = 0/373 teeth). Therefore, this finding adds additional information to the history of dental pathology in our genus and also suggests that other hominin genera may have been less susceptible to dental abscesses, potentially relating to dietary or behavioural differences

    “Experts by Experience”: The Involvement of Service Users and Families in Designing and Implementing Innovations in Family Justice

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    Drawing on international research, policy and practice this paper explores what is meant by service user involvement, how it has developed and how it has been implemented across different areas of practice. Using examples from across the health and social care fields, it reflects on how the learning from other areas of practice where service user involvement has been successful may be applied to the family justice field. The arguments presented highlight the value of taking a bottom-up approach in designing and implementing innovations in family justice, which would embrace the views of family members including children, as “service users”. It is important, however, to balance both the challenges and the opportunities offered by involving those who are ‘experts by experience’ in the Family Justice processes, in order to lead to improved services and experiences

    Effects of elevated seawater pCO2 on gene expression patterns in the gills of the green crab, Carcinus maenas

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    Background: The green crab Carcinus maenas is known for its high acclimation potential to varying environmental abiotic conditions. A high ability for ion and acid-base regulation is mainly based on an efficient regulation apparatus located in gill epithelia. However, at present it is neither known which ion transport proteins play a key role in the acid-base compensation response nor how gill epithelia respond to elevated seawater pCO2 as predicted for the future. In order to promote our understanding of the responses of green crab acid-base regulatory epithelia to high pCO2, Baltic Sea green crabs were exposed to a pCO2 of 400 Pa. Gills were screened for differentially expressed gene transcripts using a 4,462-feature microarray and quantitative real-time PCR. Results: Crabs responded mainly through fine scale adjustment of gene expression to elevated pCO2. However, 2% of all investigated transcripts were significantly regulated 1.3 to 2.2-fold upon one-week exposure to CO2 stress. Most of the genes known to code for proteins involved in osmo- and acid-base regulation, as well as cellular stress response, were were not impacted by elevated pCO2. However, after one week of exposure, significant changes were detected in a calcium-activated chloride channel, a hyperpolarization activated nucleotide-gated potassium channel, a tetraspanin, and an integrin. Furthermore, a putative syntaxin-binding protein, a protein of the transmembrane 9 superfamily, and a Cl-/HCO3 - exchanger of the SLC 4 family were differentially regulated. These genes were also affected in a previously published hypoosmotic acclimation response study. Conclusions: The moderate, but specific response of C. maenas gill gene expression indicates that (1) seawater acidification does not act as a strong stressor on the cellular level in gill epithelia; (2) the response to hypercapnia is to some degree comparable to a hypoosmotic acclimation response; (3) the specialization of each of the posterior gill arches might go beyond what has been demonstrated up to date; and (4) a re-configuration of gill epithelia might occur in response to hypercapnia
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