Structure-Function Relationships in Radiation-Induced Cell and Tissue Lesions: Special References to the Contributions of Scanning Electron Microscopy and Hematopoietic Tissue Responses

Contributions of scanning electron microscopy to the field of radiation biology are briefly reviewed and presented in terms of an overall goal to identify and characterize the structural features of radiation-induced lesions in vital cell and tissue targets. In the context of lesion production, the major radiation-elicited response sequences, the types and nature of measured end points, and governing temporal and radiobiological parameters are discussed and illustrated by using results derived from both in vitro cell systems and in vivo studies that measured tissue responses from various organ systems (respiratory, digestive, circulatory, and central nervous systems). Work in our laboratory on the nature of early and late hematopathologic tissue responses (aplastic anemia and myeloid leukemia) induced by protracted radiation exposure and the bridging effect of repair processes relative to the expression of these pathologies is highlighted

Alpha-Particle Irradiation-Induced Change in Bronchopulmonary Macrophage Morphology, In Vitro

Bronchopulmonary macrophages, isolated from canine lungs by saline lavage and grown in tissue culture for short periods, were acutely irradiated with a range of doses of either Americium-241 alpha particles (0.03-48 Gy) or 250 keV x-rays (0.5-24 Gy). Following a 24-hour reincubation and expression period, cells were examined for radiation-induced changes in overall viability, as well as in cell morphology and ultrastructure. Results indicated that neither quality of radiation had much effect on cell viability over dose ranges examined, but substantial changes in cell volume, surface topography, and cytoplasmic features were noted, especially in the alpha-particle-irradiated specimens. Results support the concept that the limiting plasma membrane of the targeted macrophage is a sensitive subcellular target for ionizing radiation, especially high-linear-energy-transfer heavy particles

SEM of Canine Chromosomes: Normal Structure and the Effects of Whole-Body Irradiation

Canine chromosomes are not only numerous (38 autosomal pairs), but they are small (compared to human chromosomes) and morphologically similar as well. Analysis of the canine karyotype by light microscopy (LM) of banded chromosomes is, thus, difficult, and the literature on the canine karyotype is scanty. In this study, we describe examination of chromosomes from normal and chronically irradiated dogs with the scanning elect ran microscope (SEM). Metaphase chromosomes from bone marrow aspirates were Giemsa-banded with either 0.025% trypsin alone or 0.1% trypsin preceded by 10% H2O2 and prepared for SEM. Examination of chromosomes from normal dogs revealed cylindrical chromosome profiles with well-defined chromatids and centromeres. The chromosome arms were consistently marked by periodic grooves that had complementary structures on sister chromatids and may represent the trypsin-sensitive chromatic regions. The quality of the preservation varied from preparation to preparation and depended on the concentration and time of trypsin treatment. Chromosomes from irradiated dogs revealed translocations, deletions, and gaps. We conclude that SEM produces images superior to LM images of canine chromosomes; SEM images can be used not only to identify individual chromosomes, but also to identify genetic lesions in the chromosomes of chronically irradiated dogs. We further conclude that the two Giemsa-banding protocols used in the present study produced variable results, although 0.025% trypsin alone appeared to give better and more consistent results than 0.1% trypsin preceded by 10% H2O2

Integrating food security into public health and provincial government departments in British Columbia, Canada

Food security policy, programs, and infrastructure have been incorporated into Public Health and other areas of the Provincial Government in British Columbia, including the adoption of food security as a Public Health Core Program. A policy analysis of the integration into Public Health is completed by merging findings from 48 key informant interviews conducted with government, civil society, and food supply chain representatives involved in the initiatives along with relevant documents and participant/direct observations. The paper then examines the results within the context of historic and international trends and theoretical models of food policy, community food security, and applied policy research. Public Health re-emerged as a driver of food security in BC—both as a key player and in positing the public’s health as a driver in food security and food systems. While Public Health’s lead role supported an increase in legitimacy for food security in BC, interviewees described a clash of cultures between Public Health and civil society. The clash of cultures occurred partly as a result of Public Health’s limited food security mandate and top down approach. Consequently civil society voice at the provincial level was marginalized. A social policy movement toward a new political paradigm—regulatory pluralism—calls for greater engagement of civil society, and for all sectors to work together toward common goals. A new, emerging policy map is proposed for analyzing the dynamics of food security and health promotion initiatives in BC

Morphologic Changes of Apoptosis Induced in Human Chronic Myelogenous Leukemia Blast Cells by SC41661A (Searle), A Selective Inhibitor of 5-Lipoxygenase

Several inhibitors of the arachidonic acid-metabolizing enzyme, 5-lipoxygenase reduce proliferation of hematopoietic and non-hematopoietic cells and cell lines and some cells undergo limited differentiation. Cells were cultured from patients with chronic myelogenous leukemia in blast crisis with the selective inhibitor of 5-lipoxygenase,SC41661A[3-{3,5-bis(1,1-dimethyl)-4-hydroxyphenyl}hiol]-N-methyl-N-[2-(2-phridinyl-propanamide)]. Cells cultured for 3 to 5 days with 40 μM SC41661A exhibited reduced cellular numbers along with ultrastructural changes and DNA laddering characteristic of apoptosis. Similar culture conditions reduced proliferation of U937 monoblastoid cells. In U937 cells, the ultrastructural features of apoptosis were not observed at 72 hours, when DNA laddering was present and cell numbers were reduced, but was present after 144 hours of culture. Dissociation between certain morphologic and biochemical sequelae of apoptosis has been described in other systems. These observations are of interest since the induction of apoptosis in dividing chronic myelogenous leukemia (CML) cells by a noncytotoxic agent suggests paradigmatically new sites for therapeutic intervention

Developmental and Radiobiologic Characteristics of Canine Multinucleated, Osteoclast-Like Cells Generated in Vitro from Canine Bone Marrow

We report here our initial observations on the growth and morphology, and developmental radiosensitivity of giant, multinucleated, osteoclast-like cells (MN-OS} generated through in vitro cultivation of hematopoietic progenitor-enriched canine bone marrow samples. Maximum cell densities of 5.5 x 103 to 6.5 x 103 MN-OS per cm2 of growth area were achieved following 10 to 14 days of culture at 37°C. Acute gamma irradiation of the initial marrow inocula resulted in significant, dose-dependent perturbations of MN-OS formation, growth, and development. Attempts to estimate radiosensitivity of MN-OS progenitors from canine marrow yielded a range of DO values from a low of 212 cGy measured at six days of culture to higher values of 405 to 542 cGy following 10 to 22 days of culture. At the intermediate times of culture (10 to 14 days}, the radiation-induced responses were clearly biphasic, reflecting either (a) the presence of multiple subpopulations of MN-OS progenitors with varying degrees of radiosensitivity or (b) the inherent biphasic nature of MN-OS development involving early progenitor cell proliferation followed by maturation and subsequent fusion. Morphologically, MN-OS generated from irradiated marrow inocula appeared only marginally altered, with alterations expressed largely in a biphasic, dose-dependent fashion in terms of smaller cell size, reduced number of nuclei, increased expression of both surface microprojections, and a unique set of crystalloid cytoplasmic inclusions. Functionally, MN-OS appeared to be impaired by irradiation of marrow progenitors, as evidenced by failure to initiate resorptive attachments to devitalized bone spicules in vitro

Early antenatal prediction of gestational diabetes in obese women: development of prediction tools for targeted intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most

Role of spatial anisotropy in design storm generation: Experiment and interpretation

Rainfall accumulation depths over a given area are strongly dependent on the shape of the storm together with its direction of advection. A method to produce design storms exhibiting anisotropic spatial scaling is presented by combining a state-of-the-art stochastic rainfall generator STEPS with the linear generalized scale invariance (GSI) notation. The enhanced model is used to create ensembles of design storms based on an extreme storm with a distinct rainband shape observed in Melbourne, Australia. Design storms are generated both with and without accounting for anisotropy. Effect of anisotropy on precipitation characteristics is studied using the entire region covered by the radar (radar scale) and at a significantly smaller catchment scale. A rainfall-runoff model is applied to route the rainfall through the catchment into streamflow. Accounting for anisotropy allows for a more realistic description of precipitation features at the radar scale. At the catchment scale, anisotropy increases the probability of high rainfall accumulations, which translates into greater flood volumes. No discernible difference was observed in streamflow characteristics after controlling for the accumulation over the catchment. This could be explained by a lower importance of anisotropy relative to other factors affecting streamflow generation, and by the difficulties in creating representative rainfall temporal properties at the catchment scale when the radar scale is used for model calibration. The proposed method provides a tool to create ensembles of design storms when the anisotropic shape of the fields is of importance.Peer reviewe

Dermal reaction and bigeminal premature ventricular contractions due to neostigmine: a case report

<p>Abstract</p> <p>Introduction</p> <p>Neostigmine is a frequently used acetylcholinesterase inhibitor administered to reverse muscular relaxation caused by nondepolarizing neuromuscular relaxants in patients recovering from general anesthesia. Severe allergic reactions and urticaria are rarely reported following the use of neostigmine bromide, and never with methylsulfate-containing drugs. In this case, bigeminal premature ventricular contractions added to urticaria provides a warning about the possibility of a life-threatening situation.</p> <p>Case presentation</p> <p>We report the case of a 23-year-old Persian woman who presented with bigeminal premature ventricular contractions along with urticarial lesions on her arm and trunk as soon as she was administered neostigmine methylsulfate after undergoing a laparoscopy for ectopic pregnancy.</p> <p>Conclusion</p> <p>This case report could be of value not only for anesthesiologists who routinely use neostigmine but also for others who administer the pharmaceutical preparation in other situations. The report presents a rare case of drug reaction following neostigmine use. As a result, one should consider any drug a probable cause of drug reaction. The preparation of resuscitative facilities, therefore, is necessary prior to the prescription of the medication.</p