Nogo-A inhibition induces recovery from neglect in rats

Neglect is a complex human cognitive spatial disorder typically induced by damage to prefrontal or posterior parietal association cortices. Behavioral treatments for neglect rarely generalize outside of the therapeutic context or across tasks within the same therapeutic context. Recovery, when it occurs, is spontaneous over the course of weeks to months, but often it is incomplete. A number of studies have indicated that anti-Nogo-A antibodies can be used to enhance plasticity and behavioral recovery following damage to motor cortex, and spinal cord. In the present studies the anti-Nogo-A antibodies IN-1, 7B12, or 11C7 were applied intraventricularly to adult rats demonstrating severe neglect produced by unilateral medial agranular cortex lesions in rats. The three separate anti-Nogo-A antibody groups were treated immediately following the medial agranular cortex lesions. Each of the three antibodies induced dramatic significant behavioral recovery from neglect relative to controls. Severing the corpus callosum to destroy inputs from the contralesional hemisphere resulted in reinstatement of severe neglect, pointing to a possible role of interhemispheric mechanisms in behavioral recovery from neglect.     

Destruction of the auditory thalamus disrupts the production of fear but not the inhibition of fear conditioned to an auditory stimulus

The auditory thalamus is part of a neural circuit that mediates the expression of fear to auditory stimuli. Bilateral lesions of the auditory thalamus prevent the expression of fear to an auditory stimulus paired with shock. The present study assessed whether bilateral lesions of the auditory thalamus would also disrupt the inhibition of fear to an auditory stimulus paired with the absence of shock. Rats were given bilateral lesions of the auditory thalamus followed by Pavlovian conditioned inhibition training in which a light was paired with shock and a noise and light compound was presented in the absence of shock. Fear and the inhibition of fear were measured with the fear-potentiated startle effect. Lesions of the auditory thalamus did not disrupt the ability of the noise to inhibit the expression of fear to the light. However, these lesions did disrupt the ability of the noise to produce fear-potentiated startle after it had been subsequently paired with shock. These results suggest that although the auditory thalamus is an essential part of a neural circuit that mediates the expression of fear to auditory stimuli, it is not an essential part of the circuit that mediates the inhibition of fear to auditory stimuli.     

Brazilian–Portuguese version of defensive style questionnaire-40 for the assessment of defense mechanisms: construct validity study

Abstract

The aim of this study is to analyze the reliability and validity of the Brazilian–Portuguese version of the Defensive Style Questionnaire (DSQ). Participants were evaluated by clinical interview and the Mini-International Neuropsychiatric Interview. Reliability was assessed by factor analysis and Cronbach's alpha. The 3-factor model's replication was tested using confirmatory factor analysis (CFA). Controls were reevaluated after 4 months to assess test–retest reliability. Subsamples were also evaluated using the Minnesota Multiphasic Personality Inventory and Defensive Functioning Scale (DFS). Factor analysis of the various defense mechanisms produced a distribution of mechanisms among the factors that was largely similar to previous analyses based on the original instrument. The 3-factor model was supported by CFA. The test–retest evaluation showed sufficient intraclass correlation for all factors. Patients used more immature and neurotic defenses than controls. There was a correlation between DFS and immature defenses. Individuals with pathological personality traits scored higher on the immature and neurotic factors than those without. The Brazilian–Portuguese version of the DSQ-40 has psychometric features that allow the use of this instrument in our culture.     

The effect of a gas leak around the endotracheal tube on the mean tracheal pressure during mechanical ventilation

Infants requiring mechanical ventilation are usually intubated with uncuffed endotracheal tubes, which permit gas to leak between the tube and the trachea. This gas leak may alter the mean pressure transmitted to the trachea by changing the pattern of airway flow and modifying the resistive behavior of the endotracheal tube. To test this hypothesis, we measured mean tracheal pressure, gas flow through the endotracheal tube, and resistance of the tube in rabbits ventilated with and without a leak. We also studied the effect of the tube size and the pattern of ventilation on these measurements. We found that a leak reduced the mean tracheal pressure by 15 to 21% with respect to the mean proximal airway pressure. This reduction was caused by an increased difference between inspiratory and expiratory flow through the endotracheal tube, and by the mean expiratory resistance of the tube being lower than its mean inspiratory resistance. The rabbits with smaller tubes had lower mean tracheal pressures. A ventilatory pattern of short inspiratory times and high peak pressures was associated with a proportionally greater decrease in mean tracheal pressure caused by the leak. These findings suggest that the mean proximal airway pressure, measured at the ventilator, may overestimate the mean tracheal pressure in the presence of a gas leak around the tube. Furthermore, the decrease in mean tracheal pressure caused by the leak may decrease oxygenation despite a constant mean proximal airway pressure.     

Cellular and molecular properties of 90Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro

PURPOSE: Anti-EGFR antibody cetuximab (C225) is used in combination with radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene-triamine-pentaacetic acid (CHX-A″-DTPA) and radiolabeling with (90)Yttrium affect the molecular and cellular function of cetuximab and improve its combined effect with external-beam irradiation (EBI). METHODS: The following cell lines were used: HNSCC UT5, SAS, FaDu, as well as A43, Chinese hamster ovary cells (CHO), and human skin fibroblast HSF7. Binding affinity and kinetics, specificity, retention, and the combination of (90)Y-cetuximab with EBI were evaluated. RESULTS: Control cetuximab and CHX-A″-DTPA-cetuximab blocked the proliferation activity of UT5 cells. In combination with EBI, CHX-A″-DTPA-cetuximab increased the radiosensitivity of UT5 to a similar degree as control cetuximab did. In contrast, in SAS and HSF7 cells neither proliferation nor radiosensitivity was affected by either of the antibodies. Binding [(90)Y]Y-CHX-A″-DTPA-cetuximab ((90)Y-cetuximab) to EGFR in HNSCC cells occurred time dependently with a maximum binding at 24?h. Retention of (90)Y-cetuximab was similar in both HNSCC cell lines; 24?h after treatment, approximately 90% of bound activity remained in the cell layer. Competition assays, using cell membranes in the absence of an internalized fraction of cetuximab, showed that the cetuximab affinity is not lost as a result of conjugation with CHX-A″-DTPA. Cetuximab and CHX-A″-DTPA-cetuximab blocked EGF-induced Y1068 phosphorylation of EGFR. The lack of an effect of cetuximab on EGF-induced Akt and ERK1/2 phosphorylation and the inhibition of irradiation (IR)-induced Akt and ERK1/2 phosphorylation by cetuximab were not affected by DTPA conjugation. (90)Y-cetuximab in combination with EBI resulted in a pronounced inhibition of colony formation of HNSCC cells. CONCLUSIONS: Conjugation of CHX-A″-DTPA to cetuximab does not alter the cellular and biological function of cetuximab. (90)Y-labeling of cetuximab in combination with EBI may improve radiotherapy outcome.     

Increased platelet Fc receptor expression in diabetes is limited to those with type 2 disease and low LDL cholesterol levels

A potential role for the platelet Fc gammaRIIA immunoreceptor (FcR) in collagen-mediated platelet activation associated with diabetes has recently been described. This study was undertaken to prospectively determine which diabetes patient population (type 1, type 2, or both) was more likely to over express platelet FcR and to determine what clinical or laboratory features characterized this population. One hundred and twenty type 2 diabetes, 135 type 1 diabetes, and 275 control patients participated in this cross-sectional study. Relative FcR expression was assessed by flow cytometry of antibody-labeled platelets. FcR expression was higher in type 2 diabetes than in type 1 diabetes or control subjects [mean+/-S.D.=15.17+/-4.66 versus 10.28+/-3.11 (p<0.05) and versus 10.33+/-2.59 (p<0.05), respectively]. This relationship was independent of sex, BMI, HDL cholesterol, triglycerides, blood pressure, glucose control, fibrinogen, and smoking. An inverse association between platelet FcR expression and plasma LDL cholesterol levels was also observed along with a modest correlation with age. Among type 2 patients there was inverse and no correlation between FcR expression and LDL levels and age respectively. Increased platelet FcR expression in type 2 diabetes may play a role in arterial vasoocclusive complications associated with this population. It is hypothesized decreased FcR expression could potentially represent a form of compensatory biological response to an adverse lipid profile in which sensitivity of platelets to collagen may be relatively down regulated in type 2 diabetes.     

Simultaneous quantification of chest wall distortion by multiple methods in preterm infants

Three methods for volume partitioning were simultaneously used to study 8 preterm infants: (1) miniature magnetometers, which measured the anteroposterior diameter of the chest wall and abdomen, (2) mercury-in-rubber strain gauges, which measured circumference changes, and (3) an inductance plethysmograph (Respitrace), which reportedly measures volume changes of a coil of fine wire placed around the chest and abdomen. Volume changes of the chest wall and abdomen were calibrated against lung volume changes measured with a pneumotachograph using a multiple linear regression (MLR) method, and the partitioning was checked by airway occlusion. The abdominal signals of the 3 systems were similar. The chest wall signals from the strain gauges and inductance plethysmograph were also similar but differed from those of the magnetometers (in 2 of the infants) primarily due to differences in the phase relationship of the signals. The 95% confidence limits for estimates of changes in lung volume by the MLR method in most infants was +/- 5% using all 3 systems. The airway occlusion check, however, could not corroborate the accuracy of volume partitioning by the magnetometers in half the infants. The minute volume displacement of the diaphragm was the same for the strain gauges and the inductance plethysmograph, ranging from 48 to 127% of the pulmonary minute ventilation, and was significantly underestimated by the magnetometers (p less than 0.001). These results suggest that distortion of the sternal portion of the chest wall, as detected by the magnetometers, represents less volumetric loss than the volume lost for the entire chest wall due to paradoxical breathing.(ABSTRACT TRUNCATED AT 250 WORDS)     

The visualization of the anterior spinal artery and its blood-stream direction during brachial vertrebral angiography

Summary The authors have reviewed 75 cases of vertebral angiography performed by retrograde brachial injection of contrast-medium. In 18 cases the anterior spinal artery was visualized. The blood-stream direction in the ascending and descending branches of the radicular arteries was estimated.

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Die Darstellung der Arteria spinalis anterior und die Richtung des Blutstromes in diesem Gefäß während der Brachialis-Angiographie

Zusammenfassung In einer Serie von 75 Fällen Vertebralis-Angiographien mit einer retrograden Injektion des Kontrastmittels in die arteria brachialis, haben die Autoren in 18 Fällen die Sichtbarmachung der arteria spinalis anterior festgestellt. Es wurde ein Versuch gemacht, die Blutstromrichtung in dem aufsteigenden und absteigenden Ast der arteria radicularis anterior zu schätzen.

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La visualisation de l'artère spinale antérieure et de sa direction du courant sanguin pendant l'angiographie vertébrale

Résumé Les auteurs ont passé en revue 75 cas d'angiographie vertébrale pratiquée par injection de produit de contraste par voie humérale rétrograde. L'artère spinale antérieure a été visualisée dans 18 cas. La direction du courant sanguin dans les branches ascendantes et descendantes des arteres radiculaires a été estimée.