Emerging roles for long noncoding RNAs in B-cell development and malignancy.

Long noncoding (lnc)RNAs have emerged as essential mediators of cellular biology, differentiation and malignant transformation. LncRNAs have a broad range of possible functions at the transcriptional, posttranscriptional and protein level and their aberrant expression significantly contributes to the hallmarks of cancer cell biology. In addition, their high tissue- and cell-type specificity makes lncRNAs especially interesting as biomarkers, prognostic factors or specific therapeutic targets. Here, we review current knowledge on lncRNA expression changes during normal B-cell development, indicating essential functions in the differentiation process. In addition we address lncRNA deregulation in B-cell malignancies, the putative prognostic value of this as well as the molecular functions of multiple deregulated lncRNAs. Altogether, the discussed work indicates major roles for lncRNAs in normal and malignant B cells affecting oncogenic pathways as well as the response to common therapeutics.

Dynamic ultrasound-guided short-axis needle tip navigation technique vs. landmark technique for difficult saphenous vein access in children: a randomised study.

Dynamic ultrasound-guided short-axis needle tip navigation is a novel technique for vascular access. After venipuncture, the needle and catheter are further advanced within the vessel lumen under real-time ultrasound guidance with constant visualisation of the needle tip in the short-axis view. This can minimise the risk of transfixing the cannulated vessel. We compared two techniques for non-visible saphenous vein cannulation under general anaesthesia in children weighing ≥ 3 kg and less than four years of age: dynamic ultrasound-guided short-axis needle tip navigation technique (ultrasound group) vs. landmark technique. Venous cannulation was performed by three experienced anaesthetists. The primary outcome measure was first-attempt success rate. Success rate within 10 min was a secondary outcome. A total of 102 patients were randomly allocated to either the ultrasound group or the landmark group. First-attempt success rate was 90% in the ultrasound group compared with 51% in the landmark group, p<0.001, difference 39%, 95% confidence interval (CI) of the difference 23-55%. Success rate within 10 min was 92% in the ultrasound group compared with 63% in the landmark group, p = 0.001, difference 29%, 95%CI of the difference 14-45%. We conclude that, when performed by experienced anaesthetists, the dynamic ultrasound-guided short-axis needle tip navigation technique improved non-visible saphenous vein cannulation in children compared with the landmark technique.

Volatile organic compounds, polycyclic aromatic hydrocarbons and elements in the air of ten urban homes.

Ten homes were monitored at regular intervals from June 1994 through April 1995 as part of a Public Health Assessment in Southeast Chicago for exposure to volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), and elements. Simultaneous 24-h indoor and outdoor samples were collected. VOCs were and analyzed using USEPA Method TO-14 with Selected Ion Monitoring Mass Spectrometry (GC/MS). PAHs were analyzed using USEPA Method TO-13 with GC/MS. Elements were collected on quartz fiber filters and analyzed by Inductively Coupled Argon Plasma (ICP) spectroscopy or Graphite Furnace Atomic Absorption (GFAA). Continuous measurements of CO2 and temperature were recorded for each indoor sample. Twenty-four h total CO2 emissions were determined from occupancy and estimated gas stove usage and were moderately correlated (R2 = 0.19) with 24 h average indoor CO2 concentrations. Modeled 24-h air exchange rates ranged from 0.04 to 3.76 air changes h-1 (ACH), with mean of 0.52 ACH. Median particle penetration was 0.89. Emission rates were calculated for each pollutant sampled. Using a detailed housing survey and field sampling questionnaires, it was possible to evaluate associations between housing characteristics and source activities, and pollutant source rates. The data indicate that several predictor variables, including mothball storage, air freshner use, and cooking activities, are reasonable predictors for emission rates for specific pollutants in the homes studied.

Vocal fold paralysis following the anterior approach to the cervical spine.

The anterior cervical approach is commonly used for access to the cervical spine. Vocal fold paralysis (VFP), a complication of this approach, is underrepresented in the literature. A review of the database of the Vanderbilt Voice Center revealed 289 patients with VFP, including 16 patients who developed paralysis as a result of an anterior cervical approach. The paralysis was on the right side in all but 1 patient. Compared to patients who developed VFP after thyroidectomy and carotid endarterectomy, patients with VFP after an anterior cervical approach have a higher incidence of aspiration and dysphagia, suggesting the presence of trauma to the superior laryngeal and pharyngeal branches as well as the recurrent branch of the vagus nerve. Two patients had partial return and 1 patient had complete return of vocal fold movement within 10 months. Of the remaining 13 patients, 8 underwent vocal fold medialization with improvement of symptoms. Two patients are 6 and 7 months postinjury and await vocal fold medialization. Two patients are 27 months and 45 months postinjury and are considering vocal fold medialization. The remaining patient was lost to follow-up. An anatomic-geometric analysis of the right and left recurrent laryngeal nerves was performed by using measurements obtained from computed tomography scans of 8 patients with idiopathic unilateral VFP, as well as experience gained through surgical and cadaveric dissections. We conclude 1) the anterior cervical approach may place multiple branches of the vagus nerve at risk; 2) because of anatomic-geometric factors, the right-sided anterior cervical approach may carry a greater risk to the ipsilateral recurrent laryngeal nerve than does the left; and 3) an understanding of the anatomy and geometry presented herein allows relatively safe exposure from either side of the neck.

Inhibition of rat passive cutaneous anaphylaxis by 3-(tetrazol-5-yl)quinolines.

Quinoline-3-carboxylic acid (3) was found to have weak oral activity in the rat passive cutaneous (PCA) assay. In an effort to increase activity, the synthesis of structurally related compounds was initiated. This led to substituted 3-(tetrazol-5-yl)quinolines, some of which are equal in potency, when given orally, to doxantrazole. Further work resulted in the synthesis of 4-oxoquinolines, one of which, 8-chloro-1,4-dihydro-4-oxo-3-(tetrazol-5-yl)quinoline (132), is 33-fold more active than disodium cromoglycate (ip) and 32-fold more active than doxantrazole (po).

Antiallergic activity of tetracyclic derivatives of quinoline-2-carboxylic acids. 1.

Substitution of 1,4-dihydro-4-oxoquinoline-2-carboxylic acid by acetyl, benzoyl, and phenylsulfonyl substituents was found to enhance activity in the rat passive cutaneous anaphylaxis assay. A further increase in activity, to equipotency with DSCG, was achieved by incorporation of the 8-benzoyl moiety into a tetracyclic structure to give 1,4-dihydro-4,11(1H,11H)-dioxoindeno[1,2-h]quinoline-2-carboxylic acid (20). In contrast, the reverse isomer 19 was found to have little activity.

Further studies on the reversibility of serum sickness cholesterol-induced atherosclerosis.

Rabbits were induced to form atheromatous cardiovascular lesions by subjecting them to treatments of a single BSA injection plus a 2-wk period of cholesterol diet, or to the diet alone. Microscopic examination of the hearts at the end of the 2-wk induction period, or after having been returned to regular diet for 5 or 8 wk, showed that lesion incidence in the cholesterol-only animall decreased markedly during the 8-wk rest period, while little change in incidence occurred in animals with lesions from the combined treatment. This finding was taken to mean that the latter type of lesion was less reversible, and therefore perhaps more pathologically significant, than the former type. It was felt that lipid deposition was not solely responsible for this prolongation, since it was present in diet-only lesions which disappeared with time, and also seemed to be disappearing from the prolonged lesions in all treatment groups. On the other hand, elastic tissue was demonstrated only in lesions arising from the combined treatment, and it is hypothesized that this feature is implicated in the prolongation of these lesions.

Effect of removal of cholesterol diet upon serum sickness-cholesterol-induced atherosclerosis.

In this report, the role of vascular allergy (i.e., hypersensitivity) in the potentiation of atherogenesis has been studied. In order to accomplish this, bovine serum albumin (BSA) was administered to rabbits in quantities sufficient to cause the occurrence of serum sickness (a type of hypersensitivity known to cause injury to the endothelial linings of certain blood vessels). This was immediately followed by the feeding of a special cholesterol-supplemented diet, which is known to be capable of initiating a high incidence of atheromatous disease in rabbits after prolonged feeding. Results indicated that those animals which received the combined treatment developed an incidence of pathology after only 2 wk of special diet which was not equaled in the diet-only control groups until they had been treated for 4 wk. This indicated that vascular allergy could potentiate lipemia-induced atherogenesis in the rabbit, and was in confirmation of an earlier study of a similar nature. Indeed, because of the relatively mild vascular injury caused by a single injection of BSA, it would seem as though vascular hypersensitivity was extremely effective in the potentiation of atherogenesis. In addition, these results may have given some indication of the degree of vascular injury necessary for the induction of irreversible atheromatous disease. While the incidence of lesions in serum sickness controls was seen to decrease with passage of time after BSA challenge, it appeared to increase after cessation of treatment in those animals which received the combined treatment of BSA plus 2 wk of cholesterol-supplemented diet. It would therefore appear that the atheromatous lesions seen as early as 2 wk after initiation of the experiment may already have been irreversible in terms of the resolution of established pathology.