Does it run in the family? - Improving radiological risk assessment in the coastal environment using taxonomic and phylogenetic perspectives in macroalgae species.

Marine macroalgae are widely used indicator species for monitoring environmental radioactivity. Empirical studies have demonstrated a range in radionuclide transfer coefficients, or concentration ratios (CRs), between taxonomic groups, however the CR values used for dose estimation assume that macroalgae are a homogenous group, represented by a single CR. This study demonstrates the presence of a taxonomic signal in macroalgae CRs for multiple anthropogenic and naturally occurring radionuclides (137Cs, 241Am, 239+240Pu, 210Po) based on a collation of available data. A Residual Maximum Likelihood (REML) mixed model was applied, producing relative estimate CRs specific to each species within the datasets. The collated data was also analysed for a phylogenetic signal, but only a weak signal was found for one radionuclide in one group (239+240Pu in Phaeophyceae). A theoretical case study using the estimated CRs and the ERICA tool was carried out to demonstrate the implications of these findings in a real-world scenario.

Enhancing radiological monitoring of 137Cs in coastal environments using taxonomic signals in brown seaweeds.

With the rapidly expanding global nuclear industry, more efficient and direct radiological monitoring approaches are needed to ensure the associated environmental health impacts and risk remain fully assessed and undertaken as robustly as possible. Conventionally, radiological monitoring in the environment consists of measuring a wide range of anthropogenically enhanced radionuclides present in selected environmental matrices and using generic transfer values for modelling and prediction that are not necessarily suitable in some situations. Previous studies have found links between taxonomy and radionuclide uptake in terrestrial plants and freshwater fish, but the marine context remains relatively unexplored. This preliminary study was aimed at investigating a similar relationship between brown seaweed, an important indicator in radiological monitoring programmes in the marine environment, and Caesium-137, an important radionuclide discharged to the marine environment. A linear mixed model was fitted using REsidual Maximum Likelihood (REML) to activity concentration data collected from literature published worldwide and other databases. The output from REML modelling was adjusted to the International Atomic Energy Agency (IAEA) quoted transfer value for all seaweed taxa in order to produce mean estimate transfer value for each species, which were then analysed by hierarchical ANalysis Of VAriance (ANOVA) based on the taxonomy of brown seaweeds. Transfer value was found to vary between taxa with increasing significance up the taxonomic hierarchy, suggesting a link to evolutionary history. This novel approach enables contextualisation of activity concentration measurements of important marine indicator species in relation to the wider community, allows prediction of unknown transfer values without the need to sample specific species and could, therefore, enhance radiological monitoring by providing accurate, taxon specific transfer values for use in dose assessments and models of radionuclide transfer in the environment.

A seafood risk tool for assessing and mitigating chemical and pathogen hazards in the aquaculture supply chain.

Intricate links between aquatic animals and their environment expose them to chemical and pathogenic hazards, which can disrupt seafood supply. Here we outline a risk schema for assessing potential impacts of chemical and microbial hazards on discrete subsectors of aquaculture-and control measures that may protect supply. As national governments develop strategies to achieve volumetric expansion in seafood production from aquaculture to meet increasing demand, we propose an urgent need for simultaneous focus on controlling those hazards that limit its production, harvesting, processing, trade and safe consumption. Policies aligning national and international water quality control measures for minimizing interaction with, and impact of, hazards on seafood supply will be critical as consumers increasingly rely on the aquaculture sector to supply safe, nutritious and healthy diets.

Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I.

The execution phase of apoptosis is characterized by marked changes in cell morphology that include contraction and membrane blebbing. The actin-myosin system has been proposed to be the source of contractile force that drives bleb formation, although the biochemical pathway that promotes actin-myosin contractility during apoptosis has not been identified. Here we show that the Rho effector protein ROCK I, which contributes to phosphorylation of myosin light-chains, myosin ATPase activity and coupling of actin-myosin filaments to the plasma membrane, is cleaved during apoptosis to generate a truncated active form. The activity of ROCK proteins is both necessary and sufficient for formation of membrane blebs and for re-localization of fragmented DNA into blebs and apoptotic bodies.

An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane.

Platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) plays an active role in the process of leukocyte migration through cultured endothelial cells in vitro and anti-PECAM-1 antibodies (Abs) inhibit accumulation of leukocytes into sites of inflammation in vivo. Despite the latter, it is still not clear at which stage of leukocyte emigration in vivo PECAM-1 is involved. To address this point directly, we studied the effect of an anti-PECAM-1 Ab, recognizing rat PECAM-1, on leukocyte responses within rat mesenteric microvessels using intravital microscopy. In mesenteric preparations activated by interleukin (IL)-1 beta, the anti-PECAM-1 Ab had no significant effect on the rolling or adhesion of leukocytes, but inhibited their migration into the surrounding extravascular tissue in a dose-dependent manner. Although in some vessel segments these leukocytes had come to a halt within the vascular lumen, often the leukocytes appeared to be trapped within the vessel wall. Analysis of these sections by electron microscopy revealed that the leukocytes had passed through endothelial cell junctions but not the basement membrane. In contrast to the effect of the Ab in mesenteric preparations treated with IL-1 beta, leukocyte extravasation induced by topical or intraperitoneal administration of the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was not inhibited by the anti-PECAM-1 Ab. These results directly demonstrate a role for PECAM-1 in leukocyte extravasation in vivo and indicate that this involvement is selective for leukocyte extravasation elicited by certain inflammatory mediators. Further, our findings provide the first in vivo indication that PECAM-1 may have an important role in triggering the passage of leukocytes through the perivascular basement membrane.

Navigating the health care system: perceptions of patients with chronic pain.

A new framework is needed for patients with chronic pain and their primary care physicians that acknowledges the individual's experiences and provides evidence-informed education and better linkages to community-based resources. This study describes the experience of 19 chronic-pain sufferers who seek relief via the health care system. Their experiences were recorded through in-depth semistructured interviews and analyzed through qualitative methods. The participants reported early optimism, then disillusionment, and finally acceptance of living with chronic pain. Both individuals with chronic pain and their health care professionals need evidence-informed resources and information on best practices to assist them to manage pain. Empathetic communication between health care professionals and individuals with chronic pain is crucial because insensitive communication negatively affects the individual, reduces treatment compliance and increases health care utilization.

A survey of prelicensure pain curricula in health science faculties in Canadian universities.

OBJECTIVE: The present exploratory, descriptive study aimed to determine the designated time for mandatory pain content in curricula of major Canadian universities for students in health science and veterinary programs before being licensed. METHOD: Major Canadian university sites (n=10) were chosen where health science faculties included at least medicine (n=10) and nursing (n=10); many also included dentistry (n=8), pharmacy (n=7), physical therapy (n=8) and/or occupational therapy (n=6). These disciplines provide the largest number of students entering the workforce but are not the only ones contributing to the health professional team. Veterinary programs (n=4) were also surveyed as a comparison. The Pain Education Survey, developed from previous research and piloted, was used to determine total mandatory pain hours. RESULTS: The majority of health science programs (67.5%) were unable to specify designated hours for pain. Only 32.5% respondents could identify specific hours allotted for pain course content and/or additional clinical conferences. The average total time per discipline across all years varied from 13 h to 41 h (range 0 h to 109 h). All veterinary respondents identified mandatory designated pain content time (mean 87 h, range 27 h to 200 h). The proportion allotted to the eight content categories varied, but time was least for pain misbeliefs, assessment and monitoring/follow-up planning. CONCLUSIONS: Only one-third of the present sample could identify time designated for teaching mandatory pain content. Two-thirds reported 'integrated' content that was not quantifiable or able to be determined, which may suggest it is not a priority at that site. Many expressed a need for pain-related curriculum resources.

Bronchial mucosal dendritic cells in smokers and ex-smokers with COPD: an electron microscopic study.

BACKGROUND: Bronchial mucosal dendritic cells (DCs) initiate and regulate immune responses to inhaled antigens, viruses and bacteria. Currently, little is known of their numbers in patients with chronic obstructive pulmonary disease (COPD). While reductions in their numbers have been reported recently in smokers with asthma, nothing is known of the effects of cigarette smoking on bronchial DCs in COPD. The present study compares DC numbers in smokers and ex-smokers with COPD. METHODS: Endobronchial biopsies were obtained from 15 patients with moderate to severe COPD (10 current smokers with median forced expiratory volume in 1 s (FEV1) 45.5% predicted (range 23-68) and 5 ex-smokers with median FEV1 30% predicted (range 21-52)), 11 non-smokers with asthma (median FEV1 102% predicted (range 89-116)) and 11 non-smoker healthy controls (median FEV1 110% predicted (range 92-135)). Transmission electron microscopy (TEM) was used to identify the total population of DCs by their ultrastructure and their number in the epithelium and subepithelium was counted. RESULTS: Median (range) DC numbers were significantly lower in current smokers with COPD in the epithelium (0.0 (0.0-156.8) cells/mm2) and the subepithelium (4.5 (0.0-63.6) cells/mm2) compared with ex-smokers with COPD (97.9 (93.5-170.3) cells/mm2 in the epithelium (p<0.05); 91.8 (38.2-283.3) cells/mm2 in the subepithelium (p<0.01)). DC numbers in ex-smokers with COPD were similar to those in subjects with atopic asthma and healthy controls (131.6 (33.3-235.5) cells/mm2 in the epithelium and 64.4 (0.0-182.4) cells/mm2 in the subepithelium for the latter). CONCLUSIONS: In COPD, bronchial mucosal DC numbers are lower in current smokers while, in those who quit, numbers are similar to non-smoking subjects with asthma and non-smoking healthy controls. The functional consequences of the reduction in mucosal DC numbers in smokers with COPD have yet to be determined.

Nitric oxide levels and ciliary beat frequency in indigenous New Zealand children.

New Zealand children's morbidity from respiratory disease is high. This study examines whether subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. A prospective study enrolled a group of healthy children who were screened for respiratory disease by questionnaire and lung function. Skin-prick tests were performed to control for atopy. Exhaled and nasal NO was measured online by a single-breath technique using chemiluminescence. Ciliary specimens were obtained by nasal brushings for assessment of structure and function. The ciliary beat frequency (CBF) (median CBF, 12.5 Hz; range, 10.4-16.8 Hz) and NO values (median exhaled NO, 5.6 ppb; range, 2.3-87.7 ppb; median nasal NO, 403 ppb; range, 34-1,120 ppb) for healthy New Zealand European (n=58), Pacific Island (n=61), and Maori (n=16) children were comparable with levels reported internationally. No ethnic differences in NO, atopy, or CBF were demonstrated. Despite an apparently normal ciliary beat, the percentage of ciliary structural defects was 3 times higher than reported controls (9%; range, 3.6-31.3%), with no difference across ethnic groups. In conclusion, it is unlikely that subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. The high percentage of secondary ciliary defects suggests ongoing environmental or infective damage.

Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors.

The antileukaemic tyrosine kinase inhibitor, imatinib, has been reported to inhibit specifically the growth of bcr-abl expressing CML progenitors at levels of 0.1-5.0 microM, by blocking the ATP-binding site of the kinase domain of bcr-abl. Inhibition of the c-abl, platelet-derived growth factor receptor and stem cell factor receptor (c-kit) tyrosine kinases by imatinib has also been reported. Here, we demonstrate that imatinib significantly inhibits in vitro monocyte/macrophage development from normal bone marrow progenitors, while neutrophil and eosinophil development was less affected. Monocyte/macrophage inhibition was observed in semisolid agar and liquid cultures at concentrations of imatinib as low as 0.3 microM. The maturation of monocytes into macrophages was also found to be impaired following treatment of cultures with 1.0 microM imatinib. Imatinib blocked monocyte/macrophage development in cultures stimulated with and without M-CSF, suggesting that inhibition of the M-CSF receptor, c-fms, by imatinib was unlikely to be responsible. Imatinib may therefore have an inhibitory activity for other kinase(s) that play a role in monocyte/macrophage differentiation. This inhibition of normal monocyte/macrophage development was observed at concentrations of imatinib achievable pharmacologically, suggesting that imatinib or closely related derivatives may have potential for the treatment of diseases where monocytes/macrophages contribute to pathogenesis.

Interaction of Mycobacterium tuberculosis with human respiratory mucosa.

OBJECTIVE: Endobronchial infection is associated with pulmonary tuberculosis in the majority of cases. We have investigated the adherence of Mycobacterium tuberculosis to the human respiratory mucosa. DESIGN: Organ cultures constructed with human tissue were infected with M. tuberculosis in the presence or absence of mycobacterial fibronectin attachment cell surface proteins and examined by scanning electron microscopy. RESULTS: M. tuberculosis adhered mainly to extracellular matrix (ECM) in areas of mucosal damage, but not to ciliated mucosa, intact extruded cells, basement membrane or collagen fibres. Bacteria also adhered to fibrous but not globular mucus and occasionally to healthy unciliated mucosa, open tight junctions and to extruded cells that had degenerated, exposing their contents. There was a significant reduction (p<0.05) in the number of bacteria adhering to ECM after pre-incubation of bacteria with fibronectin and after pre-incubation of the tissue with M. avium fibronectin attachment protein (FAP) and M. bovis antigen 85B protein, in a concentration dependent manner. The combined effect of FAP and antigen 85B protein was significantly greater than either protein alone. Bacterial adherence to fibrous mucus was not influenced by fibronectin. CONCLUSION: We conclude that M. tuberculosis adheres to ECM in areas of mucosal damage at least in part via FAP and antigen 85B protein.

The effects of unilateral ovariectomy during pregnancy on placental and fetal growth in mice.

A comparison between placental weight and number of fetuses in normal mice and those in mice unilaterally ovariectomized on the sixth day of pregnancy, revealed a relative hypertrophy of the placentae of the latter group, with a predominance of the effect in litter sizes of five or less. The weights of the fetuses in the unilaterally ovariectomized group were not significantly different from those of the controls, thus affording no evidence of a causal connection between fetal weight and gross placental weight.

Presumptive Q fever myocarditis associated with Coxiella burnetii infection of a homograft valve in the outflow tract of the right ventricle: review and case report.

A man with pulmonary atresia and a subaortic ventricular septal defect had a radical surgical repair at the age of 16 years with correction of pulmonary atresia by replacement with an aortic valve homograft. This later became infected with Coxiella burnetii. He died at the age of 27 years from renal failure caused by glomerulonephritis and was found to have a most unusual form of widespread focal myocardial degeneration with dystrophic calcification. The diagnosis of Q fever was confirmed by positive serology during life and identification of the organisms in the homograft valve after death, by histology and electron microscopy. A fatal outcome from involvement of the myocardium in Q fever is very rare, and histological evidence of such involvement, other than by embolic infarction, is almost unknown. This would also appear to be the first recorded instance of coxiella colonization of a valve in the pulmonary outflow tract.

Studies on blood lymphocytes of patients with nodular poorly differentiated lymphocytic lymphoma.

T and B lymphocytes were measured in pretreatment blood samples from patients wih nodular poorly differentiated lymphocytic lymphoma (NPDLL). There were significant differences in T cell values between control groups and patients with NPDLL. In 13 out of 20 cases of NPDLL blood lymphocytes showed abnormalities of immunoglobulin light chain expression and were considered to show an abnormal clonal expansion of B lymphocytes. The abnormal clone of B cells in the blood reflected that found in lymph nodes and could be detected in the absence of bone marrow involvement or blood lymphocytosis.

Prostatic infiltration in chronic lymphatic leukaemia.

Forty six men with chronic lymphatic leukaemia (CLL) were studied for up to seven years. Six patients required surgery for prostatic outlet obstruction. Histological examination of the prostatic chippings showed variable degrees of infiltration with small mature lymphocytes in all six patients, suggestive of a leukaemic origin for the cells. Patients with chronic lymphatic leukaemia who undergo prostatectomy may have a higher incidence of leukaemic infiltration than has been previously recognised.

T and B lymphocyte markers in effusions of patients with non-Hodgkin's lymphoma.

T and B cells were sought in effusion fluids of 13 patients with lymphoma. In T cell lymphomas (four cases) morphologically abnormal cells that formed E rosettes were present. In B cell lymphomas (nine cases) morphologically abnormal cells were present in only two cases, however immunological studies showed a reduction in T cells and monoclonal light chain immunoglobulin expression in six of nine cases.

Immunophenotype analysis of malignant histiocytosis of the intestine.

Five cases of malignant histiocytosis of the intestine and one case of true histiocytic lymphoma were studied using immunohistological techniques. In paraffin sections tumour cells in all cases were shown to contain alpha-1-antitrypsin and to express the leucocyte common antigen. Four of the five cases of malignant histiocytosis of the intestine and the case of histiocytic lymphoma expressed the epithelial membrane antigen. Cryostat sections in four cases of malignant histiocytosis of the intestine showed that most tumour cells reacted with anti-T cell monoclonal antibodies. Only a minority expressed a typical monocyte macrophage phenotype.

Correlation of lysosomal enzyme abnormalities in various forms of adult leukaemia.

Lysosomal enzyme activities were studied in cells derived from the following types of leukaemia: chronic myeloid, acute myeloid, acute myelomonocytic, acute monocytic, non-T, non-B cell acute lymphoblastic, T-cell acute lymphoblastic, B-cell chronic lymphocytic and T-cell chronic lymphocytic. Activities of beta-hexosaminidase and alpha-mannosidase were significantly higher in cells from acute monocytic and acute myelomonocytic leukaemias, and somewhat higher in the other myeloid leukaemias, when compared with control granulocytes. Activities of beta-hexosaminidase, alpha-mannosidase, alpha-fucosidase, beta-glucuronidase and acid phosphatase were markedly lower in B cells of chronic lymphocytic leukaemia when compared with control or other leukaemic lymphoid cells. On isoelectric focusing abnormal patterns of beta-hexosaminidase, alpha-mannosidase and beta-glucuronidase activities were commonly found in myeloid and non-T, non-B cell leukaemias. All patients with acute myeloid leukaemia exhibited a relative decrease in the B form of beta-hexosaminidase activity. The results described show that studies on lysosomal enzymes may assist in the classification of different types of leukaemia.

Cell receptor studies on six anaplastic tumours of the thyroid.

Cell suspensions from six anaplastic thyroid tumours were studied for expression of lymphocyte and macrophage surface markers, and results were correlated with electron microscopy, clinical extent of disease, and response to radiotherapy. The clinical presentation of the disease was similar in all six patients. In five cases, many of the cells showed surface immunoglobulin. Electron microscopy was available on three of these and showed appearances in keeping with malignant lymphoma. The single case whose cells did not show surface immunoglobulin had an entirely different ultrastructure and was probably a carcinoma. This case was the only one that did not achieve complete remission with radiotherapy and the patient died from extensive local recurrence. It is concluded that receptor techniques are of value in distinguishing between malignant lymphoma and other anaplastic tumours of the thyroid, particularly when the results are correlated with histology.