A study of phosphorylated ERK1/2 and COX‐2 in early stage (T1–T2) oral squamous cell carcinomas

Background: Histomorphological grading at the invasive front of oral squamous cell carcinomas (OSCCs) may provide useful prognostic information. In the present study, we investigated the presence and prognostic value of activated phosphorylated extracellular signal‐regulated kinases 1 and 2 (p‐ERK1/2) and cyclo‐oxygenase‐2 (COX‐2) both at the invasive front and in central/superficial parts of OSCCs. Methods: Using immunohistochemistry, we assessed the presence of p‐ERK1/2 and COX‐2 in 53 early stage OSCCs. Clinical data were recorded prospectively. The end point was disease‐free survival. Results: p‐ERK1/2 staining was present in almost all tumours. The staining was mostly nuclear in the cells of the invasive front and either nuclear or nuclear/cytoplasmic in central/superficial tumour parts. COX‐2 was observed in almost all tumours (98%) and the staining was often restricted to focal areas. Most tumours were COX‐2 negative at the invasive front. The lowest P‐value in survival analyses was P = 0.06 for p‐ERK1/2 at the invasive front. COX‐2, the histomorphological grading systems and TNM stage were of no prognostic value. Conclusion: p‐ERK1/2 was present in almost all tumours and p‐ERK1/2 may be a prognostic marker at the invasive front of OSCCs. In early stage OSCCs, most tumours did not express COX‐2 at the invasive front.     

Value of venous ultrasonic tomography in the screening for unusual emboli-causing foci

In certain cases of pulmonary embolism, phlebography of the lower extremities remains normal. The study of 219 consecutive cases of pulmonary embolism shows the advantage of venous ultrasonic tomography which, alone, enables to screen the embolic focus in 10% of the cases, either because the phlebographic data are insufficient (5%), or because the embolic focus cannot be reached with phlebography (5%), especially in deep femoral and internal saphenous thromboses. On the other hand, popliteal venous aneurysms, which represent 1% of all embolic foci in this study, are always discovered by ultrasonography. Therefore this technique appears absolutely necessary for the diagnosis of an embolic venous focus.     

Cobalamin status and its biochemical markers methylmalonic acid and homocysteine in different age groups from 4 days to 19 years

BACKGROUND: Recent data indicate that cobalamin and folate status, including the metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo marked changes during childhood, particularly during the first year. METHODS: Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were determined in a cross-sectional study of 700 children, ages 4 days to 19 years. RESULTS: During the first 6 months, serum cobalamin was lower than and plasma MMA, tHcy, and serum folate were higher than the concentrations detected in the other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy concentrations were >0.78 and >75 micro mol/L, respectively. In older children (>6 months), serum cobalamin peaked at 3-7 years and then decreased, median plasma MMA remained low (<0.26 micro mol/L), median plasma tHcy was low (<6 micro mol/L) and increased from the age of 7 years on, and serum folate gradually decreased. Plasma MMA was inversely associated with cobalamin (r = -0.4) in both age groups, but across the whole range of cobalamin concentrations, MMA was markedly higher in infants (< or =6 months) than in older children. Plasma tHcy showed a strong negative correlation to cobalamin (r = -0.52) but not to serum folate in infants < or =6 months. In older children, tHcy showed the expected association with both cobalamin (r = -0.48) and folate (r = -0.51). CONCLUSIONS: In infants 6 weeks to 6 months, concentrations of the metabolic markers MMA and tHcy were higher than in the other age groups and strongly correlated to cobalamin, whereas in older children, both makers showed correlations to cobalamin and folate concentrations documented in adults. Whether this metabolic profile in infants is explained by impaired cobalamin status, which in turn may have long-term effects on psychomotor development, remains to be addressed in intervention studies.     

Comparison of enhancement of the vestibular perilymph between gadoterate meglumine and gadobutrol at 3-Tesla in Meniere's disease

Purpose

To compare the degree of enhancement of the perilymph between two macrocyclic gadolinium-based contrast agents (gadobutrol and gadoterate meglumine) in patients with Meniere's disease at 3-T magnetic resonance imaging (MRI).

Pontine reticulospinal projections in the neonatal mouse: Internal organization and axon trajectories

We recently characterized physiologically a pontine reticulospinal (pRS) projection in the neonatal mouse that mediates synaptic effects on spinal motoneurons via parallel uncrossed and crossed pathways (Sivertsen et al. [2014] J Neurophysiol 112:1628–1643). Here we characterize the origins, anatomical organization, and supraspinal axon trajectories of these pathways via retrograde tracing from the high cervical spinal cord. The two pathways derive from segregated populations of ipsilaterally and contralaterally projecting pRS neurons with characteristic locations within the pontine reticular formation (PRF). We obtained estimates of relative neuron numbers by counting from sections, digitally generated neuron position maps, and 3D reconstructions. Ipsilateral pRS neurons outnumber contralateral pRS neurons by threefold and are distributed about equally in rostral and caudal regions of the PRF, whereas contralateral pRS neurons are concentrated in the rostral PRF. Ipsilateral pRS neuron somata are on average larger than contralateral. No pRS neurons are positive in transgenic mice that report the expression of GAD, suggesting that they are predominantly excitatory. Putative GABAergic interneurons are interspersed among the pRS neurons, however. Ipsilateral and contralateral pRS axons have distinctly different trajectories within the brainstem. Their initial spinal funicular trajectories also differ, with ipsilateral and contralateral pRS axons more highly concentrated medially and laterally, respectively. The larger size and greater number of ipsilateral vs. contralateral pRS neurons is compatible with our previous finding that the uncrossed projection transmits more reliably to spinal motoneurons. The information about supraspinal and initial spinal pRS axon trajectories should facilitate future physiological assessment of synaptic connections between pRS neurons and spinal neurons. J. Comp. Neurol. 524:1270–1291, 2016. © 2015 Wiley Periodicals, Inc.     

Effect of leukotriene D4 on nasal mucosal blood flow, nasal airway resistance and nasal secretion in humans

The possible role of leukotriene D4 (LTD4) in nasal allergy was investigated in healthy volunteers. Nasal blood flow, nasal airway resistance, nasal discharge and nasal itching and sneezing were examined. LTD4 was found to induce a dose-response related increase in nasal mucosal blood flow as measured by laser-Doppler flowmetry. Histamine exhibited similar effects on blood flow in the same concentration range. Nasal airway resistance as recorded by rhinomanometry, increased in a dose-related manner after topical LTD4. Nasal secretion was obtained by nasal lavage and estimated from a dilution principle. Topical LTD4 did not increase the amount of nasal secretion, whereas a dose-related increase was found after topical histamine. LTD4 did not cause itching, sneezing or other irritative symptoms. In conclusion, LTD4 may play a role in nasal allergy by increasing blood flow and nasal airway resistance. Itching, sneezing and discharge, however, are apparently not caused by LTD4 but can be accounted for by the release of histamine or other mediators.     

Global test for high-dimensional mediation: Testing groups of potential mediators

We address the problem of testing whether a possibly high-dimensional vector may act as a mediator between some exposure variable and the outcome of interest. We propose a global test for mediation, which combines a global test with the intersection-union principle. We discuss theoretical properties of our approach and conduct simulation studies that demonstrate that it performs equally well or better than its competitor. We also propose a multiple testing procedure, ScreenMin, that provides asymptotic control of either familywise error rate or false discovery rate when multiple groups of potential mediators are tested simultaneously. We apply our approach to data from a large Norwegian cohort study, where we look at the hypothesis that smoking increases the risk of lung cancer by modifying the level of DNA methylation.