Low-dose hypersensitivity in Chinese hamster V79 cells targeted with counted protons using a charged-particle microbeam

The Gray Laboratory charged-particle microbeam has been used to assess the clonogenic ability of Chinese hamster V79 cells after irradiation of their nuclei with a precisely defined number of protons with energies of 1.0 and 3.2 MeV. The microbeam uses a 1-mum. silica capillary collimator to deliver protons to subcellular targets with high accuracy. The detection system is based on a miniature photomultiplier tube positioned above the cell dish, which detects the photons generated by the passage of the charged particles through an 18-mum-thick scintillator placed below the cells. With this system, a detection efficiency of greater than 99% is achieved. The cells are plated on specially designed dishes (3-mum-thick Mylar base), and the nuclei are identified by fluorescence microscopy. After an incubation period of 3 days, the cells are revisited individually to assess the formation of colonies from the surviving cells. For each energy investigated, the survival curve obtained for the microbeam shows a significant deviation below I Gy from a response extrapolated using the LQ model for the survival data above 1 Gy. The data are well fitted by a model that supports the hypothesis that radioresistance is induced by low-dose hypersensitivity. These studies demonstrate the potential of the microbeam for performing studies of the effects of single charged particles on cells in vitro. The hypersensitive responses observed are comparable with those reported by others using different radiations and techniques. (C) 2001 by Radiation Research Society.

Cough hypersensitivity syndrome is an important clinical concept:a pro/con debate

The major etiologies of chronic cough are generally accepted to consist of upper airway cough syndrome (formerly postnasal drip syndrome), eosinophilic airway inflammation (asthma, nonasthmatic eosinophilic bronchitis), and gastroesophageal reflux disease (GERD). However, only a small percentage of patients with these very common conditions suffers from chronic cough. Furthermore, acute cough due to viral upper respiratory tract infection (URI) is almost always a transient, self-limited condition, yet in a small subgroup of patients, URI heralds the onset of chronic, refractory cough. The cough hypersensitivity syndrome has been proposed to explain the occurrence of chronic cough in a subgroup of patients exposed to the same putative triggers as the vast majority of the population in whom chronic cough does not result. Although conceptually the cough hypersensitivity syndrome may be intellectually satisfying, differences of opinion remain as to whether this newly recognized entity is of clinical significance, i.e., useful for the treatment of patients suffering from chronic cough. The Third American Cough Conference, held in New York in June 2011, provided an ideal forum for the debate of this issue between two internationally recognized authorities in the field of cough.

Attention-based modulation of tactile stimuli: A comparison between prefrontal lesion patients and healthy age-matched controls

Objectives: To investigate the role of the prefrontal cortex in attention-based modulation of cortical somatosensory processing.

Methods: Six prefrontal stroke patients were compared with eleven neurologically intact older adults during a vibrotactile discrimination task. All subjects attended to stimuli on one digit while ignoring distracter stimuli on a separate digit of the same hand. Subjects were required to report infrequent targets on the attended digit only. Throughout testing electroencephalography was used to measure event-related potentials for both task-relevant and irrelevant stimuli.

Results: Prefrontal patients demonstrated significant changes in cortical somatosensory processing based on attention compared to age-matched controls. This was evident both in early unimodal somatosensory processing (i.e. P100) and in later cortical processing stages (i.e. long-latency positivity). Moreover, there was a tendency towards a tonic loss of inhibition over early somatosensory cortical processing (i.e. P50).

Conclusions: The attention-based modulation noted for neurologically intact older adults was absent in prefrontal lesion patients.

Significance: The present study highlights the important role of prefrontal regions in sustaining inhibition over early sensory cortical processing stages and in modifying somatosensory transmission based on task-relevance. Notably these deficits extend beyond those previously shown to occur as a function of age.

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area.

Inhabiting Sound: Tactile-sonic links in musical meaning

Connections can be suggested between music’s occupation of physical space, its relative ‘presence’ (using Edward Hall’s notion of proxemics), and the various senses of movement which pervade it. Movement might be seen to operate with respect to music at a variety of levels of metaphorisation – as increasingly complex chains of analogy which point back to our early physical experience of the world. But of course music is, fundamentally, action. Humans put energy into systems - external or internal to themselves - which transduce that energy into the movement of air. At the acoustic level music is, emphatically and unmetaphorically, movement. Perhaps such simple physical perceptions form one route through which we might understand and explore shared senses of meaning and their capacity for ‘transduction’ between multiple individuals. Our (developmentally) early sensory models of the world, built from encounters with its physical resistances and affordances, might be a route to understanding our more clearly encultured and abstracted ('higher' level) understandings of music.

Neural dysfunction following respiratory viral infection as a cause of chronic cough hypersensitivity

Respiratory viral infections are a common cause of acute coughing, an irritating symptom for the patient and an important mechanism of transmission for the virus. Although poorly described, the inflammatory consequences of infection likely induce coughing by chemical (inflammatory mediator) or mechanical (mucous) activation of the cough-evoking sensory nerves that innervate the airway wall. For some individuals, acute cough can evolve into a chronic condition, in which cough and aberrant airway sensations long outlast the initial viral infection. This suggests that some viruses have the capacity to induce persistent plasticity in the neural pathways mediating cough. In this brief review we present the clinical evidence of acute and chronic neural dysfunction following viral respiratory tract infections and explore possible mechanisms by which the nervous system may undergo activation, sensitization and plasticity.