Expert statement and assessment of medical impairment in work-related pulmonary disease

The Norwegian Societies of Thoracic Medicine and Occupational Medicine established a working group to standardise diagnostic procedures and evaluation of work-related respiratory disorders. In cases of suspected work-related diseases the physician may be asked by the National Insurance Administration or an insurance company to make a statement which will be one of the documents used to decide the patient's right to compensation benefit. We discuss the role of the physician as an independent expert. This is different from his role as clinician. The statement should include a balanced presentation of information from different sources, including health and occupational history, and the employer's information about the work environment (quantitative and qualitative exposure data). The statement must also include the results of a clinical examination and an assessment of functional status based on objective tests. The paper contains recommendations for evaluation of permanent impairment in light of the present Norwegian laws and regulations.     

Identification and analysis of wax esters by mass spectrometry

Several ions in the mass spectra of wax esters were related to the molecular structures. Assigned structures of ions were confirmed by deuterium labeling. A simple, direct method for quantititive analyses of mixtures was developed. The method involved a comparison of sets of three ions, RCO₂H⁺, RCO₂H₂ ⁺ and [R′−1]⁺ from all compounds in the mixture. The method was found applicable for mixtures of unsaturated wax esters after reduction with tetradeuterio hydrazine. Presented in part before the ISF-AOCS World Congress, Chicago, September 1970. Part III of a series of mass spectrometry of lipids. For VI see Lipids.     

A Novel Nanoprobe for Multimodal Imaging Is Effectively Incorporated into Human Melanoma Metastatic Cell Lines

To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T₁ relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.     

Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy

There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. “Adherent” cancer cell lines frequently release “free-floating” cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population. In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis.     

SIDS cases have increased levels of interleukin-6 in cerebrospinal fluid

Cerebrospinal fluid (CSF) from 20 infants who died of sudden infant death syndrome (SIDS), 7 cases of infectious death and 5 cases of violent death were examined with respect to concentrations of interleukin-6 (IL-6). The measurements were performed by ELISA. IL-6 levels in SIDS were significantly lower than in infectious death (p < 0.02), but significantly higher than in violent death (p < 0.02). Since IL-6 plays an important role in immune responses and may induce fever, the findings may suggest that immune activation plays a role in SIDS. The presence of cytokines in the central nervous system (CNS) may cause respiratory depression, especially in vulnerable infants.     

Plant availability of inorganic and organic selenium fertiliser as influenced by soil organic matter content and pH

The objective of the present study was to investigate the influence of soil organic matter content and pH on plant availability of both inorganic and organic selenium (Se) fertilisers. Further, the risk of Se leaching after application of inorganic Se fertiliser was evaluated. A new interpretation of an older field study at different sites in Southern Norway showed that organic C was correlated with grain Se concentration in wheat, barley and oats, explaining up to 60% of the variation in Se concentration. Pot experiments with a peat soil, a loam soil and a peat/loam soil mixture were conducted for the present study at a range of pH values between pH 5 and 7. Below pH 6, Se uptake from added Se fertiliser was higher in the soil types with high organic matter content than in the loam. The opposite occurred at a soil pH above 6, where Se uptake was higher in the loam than in the peat soil. A simple leaching experiment after one growing season confirmed the findings of the pot experiments that Se availability in the loam soil with a relatively low organic matter content increased with increasing pH, whereas it decreased in the peat soil. Neither Se yeast, nor pure Se methionine, used as organic Se fertiliser, resulted in any significant uptake of Se when added at concentrations similar to the inorganic Se applications.     

A field deployable, multiplexed Bragg grating sensor system used in an extensive highway bridge monitoring evaluation tests

A multiplexed optical fiber Bragg grating sensor system with a measurement bandwidth of up to 200 Hz enabling dynamic loading events, e.g., road traffic, to be observed has been designed, installed, and tested over an 18-month period on a 346-m road bridge in Norway, for design verification and structural integrity monitoring purposes. A network of 32 fiber Bragg sensors was surface bonded along with a corresponding set of resistive strain gauges for comparative tests to be made. The wavelength data were calibrated against two thermally stabilized (/spl sim/0.15 pm) reference gratings, which rejected common mode noise and provided absolute wavelength scaling. These data provides independent strain and temperature information. Long-term test results showed good linearity and repeatability of <10 /spl mu//spl epsiv/ over the test period with a precision of /spl plusmn/5 /spl mu//spl epsiv/ and a resolution of /spl plusmn/1 /spl mu//spl epsiv/. The readings from the FBG sensors were comparable to those from the foil gauge sensors to within /spl plusmn/4 /spl mu//spl epsiv/.     

Cabozantinib Is Effective in Melanoma Brain Metastasis Cell Lines and Affects Key Signaling Pathways

Melanomas have a high potential to metastasize to the brain. Recent advances in targeted therapies and immunotherapies have changed the therapeutical landscape of extracranial melanomas. However, few patients with melanoma brain metastasis (MBM) respond effectively to these treatments and new therapeutic strategies are needed. Cabozantinib is a receptor tyrosine kinase (RTK) inhibitor, already approved for the treatment of non-skin-related cancers. The drug targets several of the proteins that are known to be dysregulated in melanomas. The anti-tumor activity of cabozantinib was investigated using three human MBM cell lines. Cabozantinib treatment decreased the viability of all cell lines both when grown in monolayer cultures and as tumor spheroids. The in vitro cell migration was also inhibited and apoptosis was induced by cabozantinib. The phosphorylated RTKs p-PDGF-Rα, p-IGF-1R, p-MERTK and p-DDR1 were found to be downregulated in the p-RTK array of the MBM cells after cabozantinib treatment. Western blot validated these results and showed that cabozantinib treatment inhibited p-Akt and p-MEK 1/2. Further investigations are warranted to elucidate the therapeutic potential of cabozantinib for patients with MBM.