Search

Circular RNAs (circRNAs) are a class of single-stranded RNAs with a contiguous structure that have enhanced stability and a lack of end motifs necessary for interaction with various cellular proteins. Here, we show that unmodified exogenous circRNA is able to bypass cellular RNA sensors and thereby avoid provoking an immune response in RIG-I and Toll-like receptor (TLR) competent cells and in mice. The immunogenicity and protein expression stability of circRNA preparations are found to be dependent on purity, with small amounts of contaminating linear RNA leading to robust cellular immune responses. Unmodified circRNA is less immunogenic than unmodified linear mRNA in vitro, in part due to the evasion of TLR sensing. Finally, we provide the first demonstration to our knowledge of exogenous circRNA delivery and translation in vivo, and we show that circRNA translation is extended in adipose tissue in comparison to unmodified and uridine-modified linear mRNAs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The authors have demonstrated that patients with bronchial asthma may react to diluent provocative challenge. The pattern of airway response to diluent was found to be reproducible. The data herewith presented suggest that the baseline airway obstruction in adult asthma is highly variable but the degree of baseline obstruction is not related to the response to diluent challenge.

The intent of this investigation was to determine the acute effect on the airways of a single dose of intravenous corticosteroid in patients with severe bronchospasm. Following the intravenous injection of corticosteroid the initial response occurred at one to two hours and peaked at four hours. Significant changes occurred at four to six hours in central airways and in smaller airways.

This study was designed to analyze the airway response to an aerosolized diluent in patients with asthma. Fifty percent of the patients responded to diluent with less than a 10% variation from baseline (non responders), but 20% of the patients responded with more than a 25% difference from baseline (responders). This study stresses the need for control data with diluent prior to bronchial challenge with a provocative agent.

In two cases of baker's asthma pulmonary hypersensitivity was found to the fungi Alternaria and Aspergillus. Provocative bronchial challenge revealed a dual response; an immediate and an Arthus type hypersensitivity to Aspergillus in the first case. A primary binding assay revealed high titres of anti-Aspergillus antibody in the serum. In the second case intradermal and bronchial challenge suggested an immediate type I hypersensitivity response to Alternaria. The suspected organisms were present in the room air of the bakeries. It is suggested that an immunological response to these airborne fungi may have contributed to the pathogenesis of baker's asthma.

Intravenous isoproterenol was infused into 7 adult asthmatic patients with refractory bronchial obstruction. Over a dose range of 0.0375 to 0.225 mug per kilogram per minute, maximal bronchodilator effect (or reversal of effect) occurred within 2 to 5 minutes of starting (or stopping) the infusion. Obstruction to airflow improved with each increment of dose. Average heart rate reached a maximum at 0.075 mug per kilogram per minute. Over the lower dose range alveolar to arterial oxygen gradients widened and heart rate increased; over the higher dose range, as heart rate plateaued, bronchodilator effect continued and oxygen gradient narrowed. When combined with adequate oxygenation and continual monitoring of cardiac rhythm and blood pressure, intravenous isoproterenol appears safe for asthmatic patients. Major advantages are (1) administration of bronchodilator to airways not reached by inhalation, (2) prompt onset and offset of effects, and (3) reversal of undesirable side effects. The use of intravenous isoproterenol may obviate the need for intubation and ventilatory assist.

The airway response to inhaled antigen was measured in asthmatic patients at 5, 10 ad 20 minutes following bronchial challenges. The over-all frequency of positive responses in the 26 individual challenges was 27%. There were no significant differences between the 5-, 10- or 20-minute responses. Patients with positive responses to bronchial challenge manifested high grade skin reactivity by intradermal tests. Positive responses to bronchial challenge occurred only at 1 X 10(-3) weight/volume (w/v) concentration of inhaled antigen. Although the degree of methacholine reactivity was related to positive antigen challenge, two subjects with a positive challenge had minimal methacholine reactivity.

Changes in lung mechanics were measured in asthmatic adults before and after a 10-day course of daily and a three-week course of alternate day adrenocortical steroid therapy. All patients improved after the 10 days of therapy. This response continued during the a.m. measurements on the alternate day regimen with further improvement through the afternoon of the treatment day. In the afternoon of the day off corticosteroid therapy there was a deterioration in flow rates.

The airway response to methacholine was measured in 27 asthmatics. Selected indices of airway response were measured at 5-, 10- and 20-minute intervals and at three concentrations of methacholine. The mean change from control was significant at all three concentrations and there were no significant differences between time intervals. High correlations were obtained between all indices of airway response to methacholine challenge.

A captive pilot whale emptied as much as 88 percent of lung gas passively, without the aid of expiratory muscles. Level or decreasing pressures in the esophagus during expiration, and in the blowhole at the onset of expiration, revealed the driving force of expiration to be solely elastic recoil. Active muscular reexpansion of the lungs ensued immediately. Expiration and inspiration were completed in about I second.