Anti-idiotypic treatment of BALB/c mice induces CRIa-bearing suppressor cells with altered Igh-restricted function

The ABA-specific antibody response of A/J mice (Igh Ie) is dominated by the CRIa idiotype. In contrast, BALB/c mice (Igh Ia) do not produce CRIa-bearing anti-ABA antibodies after antigenic challenge. We have shown previously that treatment with rabbit anti-CRIa (R-anti-CRIa) induces the expression of "CRIa-like" anti-arsonate antibodies in BALB/c mice. In the present report, we demonstrate that R-anti-CRIa treatment enables BALB/c mice to respond to A/J ABA-specific first-order suppressor molecules (TsF1). Manipulated BALB/c also produced CRIa bearing ABA-specific immune response. Thus, R-anti-CRIa treatment induces a change in the characteristic Igh restriction pattern typically seen in this system. These data suggest that Igh restriction in the ABA-specific T suppressor cell pathway is the result of CRIa+ dominance in the T suppressor cell response of A/J mice. The effectiveness of idiotypic manipulation in inducing the expression of a given idiotype at both the B cell and T suppressor cell levels is discussed.     

Hundred and eighty years of fleet dynamics in the Belgian sea fisheries

Understanding the impact of fisheries on the commercial fish stocks requires detailed catch statistics and data on the dynamics of fleet and catch effort, at least before industrial fishing started. Most time-series on the fleet dynamics start after the 1980s, at times when major changes in fleet characteristics had already taken place. In the present paper, the results of the integration of data on fleet size (from 1830), tonnage (from 1842) and engine power (kW, from 1912) of the Belgian sea fisheries fleet are presented. The decrease in fleet size and changes in overall tonnage and engine power since the beginning of the reconstructed time-series, are quantified. The data show that the decrease in fleet size (?85 %) and in overall engine power (?5 %) was compensated by an increase in average tonnage per vessel (×10 increase) and in average engine power per vessel (×6 increase). The overall fishing effort of the fleet expressed as the total number of days spent at sea has decreased by approximately ?84 % between 1938 and 2010, while the average amount of fish landed per day per vessel (1,000 kg in 2008–2010) has at least doubled in the same period. The data reconstruction provides a unique view on the dynamics in the sea fisheries fleet of Belgium over 180 years and the political and social events associated to these changes.     

Brain-State-Dependent Modulation of Neuronal Firing and Membrane Potential Dynamics in the Somatosensory Thalamus during Natural Sleep

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Phylogenetic relationships within the Mysidae (Crustacea, Peracarida, Mysida) based on nuclear 18S ribosomal RNA sequences

Species of the order Mysida (Crustacea, Peracarida) are shrimp-like animals that occur in vast numbers in coastal regions of the world. The order Mysida comprises 1,053 species and 165 genera. The present study covers 25 species of the well-defined Mysidae, the most speciose family within the order Mysida. 18S rRNA sequence analysis confirms that the subfamily Siriellinae is monophyletic. On the other hand the subfamily Gastrosaccinae is paraphyletic and the subfamily Mysinae, represented in this study by the tribes Mysini and Leptomysini, consistently resolves into three independent clades, and hence is clearly not monophyletic. The tribe Mysini is not monophyletic either, and forms two clades of which one appears to be closely related to the Leptomysini. Our results are concordant with a number of morphological differences urging a taxonomic revision of the Mysidae.     

Purification and properties of a phospholipase A2/lipase preferring phosphatidic acid,bis(monoacylglycerol) phosphate,and monoacylglycerol from rat testis

Phospholipase A(2) (PLA(2)) was purified to homogeneity from the supernatant fraction of rat testis homogenate. The purified 63-kDa enzyme did not require Ca(2+) ions for activity and exhibited both phosphatidic acid-preferring PLA(2) and monoacylglycerol lipase activities with a modest specificity toward unsaturated acyl chains. Anionic detergents enhanced these activities. Serine-modifying irreversible inhibitors, (p-amidinophenyl) methanesulfonyl fluoride and methylarachidonyl fluorophosphonate, inhibited both activities to a similar extent, indicating a single active site is involved in PLA(2) and lipase activities. The sequence of NH(2)-terminal 12 amino acids of purified enzyme was identical to that of a carboxylesterase from rat liver. The optimal pH for PLA(2) activity (around 5.5) differed from that for lipase activity (around 8.0). At pH 5.5 the enzyme also hydrolyzed bis(monoacylglycerol) phosphate, or lysobisphosphatidic acid (LBPA), that has been hitherto known as a secretory PLA(2)-resistant phospholipid and a late endosome marker. LBPA-enriched fractions were prepared from liver lysosome fractions of chloroquine-treated rats, treated with excess of pancreatic PLA(2), and then used for assaying LBPA-hydrolyzing activity. LBPA and the reaction products were identified by microbore normal phase high performance liquid chromatography/electrospray ionization ion-trap mass spectrometry. These enzymatic properties suggest that the enzyme can metabolize phosphatidic and lysobisphosphatidic acids in cellular acidic compartments.     

A prospective cluster-randomized trial to implement the Canadian CT Head Rule in emergency departments

Background

The Canadian CT Head Rule was developed to allow physicians to be more selective when ordering computed tomography (CT) imaging for patients with minor head injury. We sought to evaluate the effectiveness of implementing this validated decision rule at multiple emergency departments.

Methods

We conducted a matched-pair cluster-randomized trial that compared the outcomes of 4531 patients with minor head injury during two 12-month periods (before and after) at hospital emergency departments in Canada, six of which were randomly allocated as intervention sites and six as control sites. At the intervention sites, active strategies, including education, changes to policy and real-time reminders on radiologic requisitions were used to implement the Canadian CT Head Rule. The main outcome measure was referral for CT scan of the head.

Results

Baseline characteristics of patients were similar when comparing control to intervention sites. At the intervention sites, the proportion of patients referred for CT imaging increased from the “before” period (62.8%) to the “after” period (76.2%) (difference +13.3%, 95% CI 9.7%–17.0%). At the control sites, the proportion of CT imaging usage also increased, from 67.5% to 74.1% (difference +6.7%, 95% CI 2.6%–10.8%). The change in mean imaging rates from the “before” period to the “after” period for intervention versus control hospitals was not significant (p = 0.16). There were no missed brain injuries or adverse outcomes.

Interpretation

Our knowledge–translation-based trial of the Canadian CT Head Rule did not reduce rates of CT imaging in Canadian emergency departments. Future studies should identify strategies to deal with barriers to implementation of this decision rule and explore more effective approaches to knowledge translation. (ClinicalTrials.gov trial register no. NCT00993252)More than six million instances of head and neck trauma are seen annually in emergency departments in Canada and the United States.¹ Most are classified as minimal or minor head injury, but in a very small proportion, deterioration occurs and neurosurgical intervention is needed for intracranial hematoma.^2,3 In recent years, North American use of computed tomography (CT) for many conditions in the emergency department, including minor head injury, has increased five-fold.^1,4 Our own Canadian data showed marked variation in the use of CT for similar patients.⁵ Over 90% of CT scans are negative for clinically important brain injury.^6–8 Owing to its high volume of usage, such imaging adds to health care costs. There have also been increasing concerns about radiation-related risk from unnecessary CT scans.^9,10 Additionally, unnecessary use of CT scanning compounds the Canadian problems of overcrowding of emergency departments and inadequate access to advanced imaging for nonemergency outpatients.Clinical decision rules are derived from original research and may be defined as tools for clinical decision-making that incorporate three or more variables from a patient’s history, physical examination or simple tests.^11–13 The Canadian CT Head Rule comprises five high-risk and two medium-risk criteria and was derived by prospectively evaluating 3121 adults with minor head injury (Figure 1) (Appendix 1, available at www.cmaj.ca/cgi/content/full/cmaj.091974/DC1).⁶ The resultant decision rule was then prospectively validated in a group of 2707 patients and showed high sensitivity (100%; 95% confidence interval [CI ] 91–100) and reliability.¹⁴ The results of its validation suggested that, in patients presenting to emergency departments with minor head trauma, a rate of usage of CT imaging as low as 62.4% was possible and safe.Open in a separate windowFigure 1The Canadian CT Head Rule, as used in the study. Note: CSF = cerebrospinal fluid, CT = computed tomography, GCS = Glasgow Coma Scale.Unfortunately, most decision rules are never used after derivation because they are not adequately tested in validation or implementation studies.^15–19 We recently successfully implemented a similar rule, the Canadian C-Spine Rule, at multiple Canadian sites.²⁰ Hence, the goal of the current study was to evaluate the effectiveness and safety of an active strategy to implement the Canadian CT Head Rule at multiple emergency departments. We wanted to test both the impact of the rule on rates of CT imaging and the effectiveness of an inexpensive and easily adopted implementation strategy. In addition, we wanted to further evaluate the accuracy of the rule.     

In vivo imaging of apoptosis in oncology: an update

In this review, data on noninvasive imaging of apoptosis in oncology are reviewed. Imaging data available are presented in order of occurrence in time of enzymatic and morphologic events occurring during apoptosis. Available studies suggest that various radiopharmaceutical probes bear great potential for apoptosis imaging by means of positron emission tomography and single-photon emission computed tomography (SPECT). However, for several of these probes, thorough toxicologic studies are required before they can be applied in clinical studies. Both preclinical and clinical studies support the notion that 99mTc-hydrazinonicotinamide-annexin A5 and SPECT allow for noninvasive, repetitive, quantitative apoptosis imaging and for assessing tumor response as early as 24 hours following treatment instigation. Bioluminescence imaging and near-infrared fluorescence imaging have shown great potential in small-animal imaging, but their usefulness for in vivo imaging in humans is limited to structures superficially located in the human body. Although preclinical tumor-based data using high-frequency-ultrasonography (US) are promising, whether or not US will become a routinely clinically useful tool in the assessment of therapy response in oncology remains to be proven. The potential of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for imaging late apoptotic processes is currently unclear. Neither 31P MRS nor 1H MRS signals seems to be a unique identifier for apoptosis. Although MRI-measured apparent diffusion coefficients are altered in response to therapies that induce apoptosis, they are also altered by nonapoptotic cell death, including necrosis and mitotic catastrophe. In the future, rapid progress in the field of apoptosis imaging in oncology is expected.     

Tumor-associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma

Background

A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC.

Methodology/Principal Findings

Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a “microglia-like” appearance on these cells which we termed “Ramified TAMs” (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells.

Conclusion

ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined.     

A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

Mouse myocardial infarction (MI) models are frequently used research tools. The most commonly applied model is coronary artery ligation. However, coronary ligation often gives rise to apical aneurysmatic infarcts of variable size. Other infarct models include cryoinfarction, which produces reproducible infarcts of the anterior wall. Thus far, this model has not been extensively described in mice. Therefore, we developed a murine cryoinfarction model and compared it with coronary ligation. Studies were performed under isoflurane anesthesia with a follow-up of 4 and 8 wk. Cryoinfarction was induced using a 2- or 3-mm cryoprobe. Two-dimensional guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and end point. At end point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histological and morphometric analyses of infarct and remote areas were performed. At 4 wk, 3-mm cryoinfarction resulted in decreased LV fractional shortening as well as decreased global LV contractility and relaxation, which was comparable with coronary ligation. No adverse remodeling was observed at this time point, in contrast with the ligation model. However, progressive LV remodeling occured between 4 and 8 wk after cryoinfarction with a further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, cone-shaped infarcts with reperfusion at the macrovascular level. These results indicate that the cryoinfarction model represents the anterior myocardial infarct with modest adverse remodeling and may thus be representative for infarcts encountered in clinical practice.