The Annals of otology, rhinology, and laryngology, 2003
Although complete or near-complete olfactory loss has been extensively documented and described, ... more Although complete or near-complete olfactory loss has been extensively documented and described, few published reports have documented severe generalized gustatory loss (across qualities and neural fields) with rigorous psychophysical testing, and none have explored the prevalence or causes of such losses in a large clinical population. This study retrospectively reviews our chemosensory clinic's experience of 1,176 patients evaluated for complaints of chemosensory dysfunction in order to address these issues. Our series confirms that despite the complex, bilateral innervation and regenerative capacity of the gustatory system, severe generalized taste loss does occur as a clinical entity, albeit rarely: only 0.85% (n = 10) of our patients evidenced such a deficit, as compared to 32% (n = 371) who were found to have a profound olfactory deficit. Combinations of systemic and/or acute events may underlie many cases of severe taste loss, and in half of our cases, these patients evid...
Transduction mechanisms were investigated in human olfactory neurons by determining characteristi... more Transduction mechanisms were investigated in human olfactory neurons by determining characteristics of odorant-induced changes in intracellular calcium concentration ([Ca2+]i). Olfactory neurons were freshly isolated from nasal biopsies, allowed to attach to coverslips, and loaded with the calcium-sensitive indicator fura-2. Changes in [Ca2+]i were studied in response to exposure to individual odors, or odorant mixtures composed to distinguish between transduction pathways mediated by adenosine 3'5'-monophosphate (c& mix A) or inositol 1,4,5-trisphosphate (InsP3; mix B). Overall, 52% of biopsies produced one or more odorant-responsive olfactory neurons, whereas 24% of all olfactory neurons tested responded to odorant exposure with a change in [Ca2+]i. As in olfactory neurons from other species, the data suggest that odorant exposure elicited calcium influx via second-messenger pathways involving cAMP or InsP3. Unlike olfactory neurons from other species that have been tested...
We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulat... more We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in 2 age groups of younger (≤ 45 years) and older (≥ 60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to 2 odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects' absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in peripheral cellular specificity may impact odor discrimination and olfactory adaptation in the elderly. It is also possible that chronic adaptation as a result of reduced specificity contributes to observed declines in absolute sensitivity.
Protein kinases A and C have been postulated to exert multiple effects on different elements of s... more Protein kinases A and C have been postulated to exert multiple effects on different elements of signal transduction pathways in olfactory receptor neurons. However, little is known about the modulation of olfactory responses by protein kinases in intact olfactory receptor neurons. To further elucidate the details of the modulation of odorant responsiveness by these protein kinases, we investigated the action of two protein kinase inhibitors: H89, an inhibitor of protein kinase A, and N-myristoylated EGF receptor, an inhibitor of protein kinase C, on odorant responsiveness in intact olfactory neurons. We isolated individual olfactory neurons from the adult human and rat olfactory epithelium and measured responses of the isolated cells to odorants or biochemical activators that have been shown to initiate cyclic AMP or inositol 1,4,5-trisphospate production in biochemical preparations. We employed calcium imaging techniques to measure odor-elicited changes in intracellular calcium that occur over several seconds. In human olfactory receptor neurons, the protein kinase A and C inhibitors affected the responses to different sets of odorants. In rats, however, the protein kinase C inhibitor affected responses to all odorants, while the protein kinase A inhibitor had no effect. In both species, the effect of inhibition of protein kinases was to enhance the elevation and block termination of intracellular calcium levels elicited by odorants. Our results show that protein kinases A and C may modulate odorant responses of olfactory neurons by regulating calcium fluxes that occur several seconds after odorant stimulation. The effects of protein kinase C inhibition are different in rat and human olfactory neurons, indicating that species differences are an important consideration when applying data from animal studies to apply to humans.
Acceptance of and expressed preference for varying levels of salt (NaCl) were assessed among chil... more Acceptance of and expressed preference for varying levels of salt (NaCl) were assessed among children 3-6 years of age. 20 children received 0, 0.17, and 0.34 M NaCl in aqueous solution, and 20 received these same NaCl concentrations in a soup broth. In both groups, children were asked to ingest as much as they wanted to each stimulus during brief, sequential presentations and to indicate which stimulus they preferred in a series of paired-comparison presentations. A striking, context-specific reaction to the taste of salt was observed on both measures. Children in this age group strongly rejected even the moderate level of salt in water relative to unsalted water. In contrast, the most highly salted soup was well accepted and preferred to either unsalted or moderately salted soup by the majority of children.
The Annals of otology, rhinology, and laryngology, 2003
Although complete or near-complete olfactory loss has been extensively documented and described, ... more Although complete or near-complete olfactory loss has been extensively documented and described, few published reports have documented severe generalized gustatory loss (across qualities and neural fields) with rigorous psychophysical testing, and none have explored the prevalence or causes of such losses in a large clinical population. This study retrospectively reviews our chemosensory clinic's experience of 1,176 patients evaluated for complaints of chemosensory dysfunction in order to address these issues. Our series confirms that despite the complex, bilateral innervation and regenerative capacity of the gustatory system, severe generalized taste loss does occur as a clinical entity, albeit rarely: only 0.85% (n = 10) of our patients evidenced such a deficit, as compared to 32% (n = 371) who were found to have a profound olfactory deficit. Combinations of systemic and/or acute events may underlie many cases of severe taste loss, and in half of our cases, these patients evid...
Transduction mechanisms were investigated in human olfactory neurons by determining characteristi... more Transduction mechanisms were investigated in human olfactory neurons by determining characteristics of odorant-induced changes in intracellular calcium concentration ([Ca2+]i). Olfactory neurons were freshly isolated from nasal biopsies, allowed to attach to coverslips, and loaded with the calcium-sensitive indicator fura-2. Changes in [Ca2+]i were studied in response to exposure to individual odors, or odorant mixtures composed to distinguish between transduction pathways mediated by adenosine 3'5'-monophosphate (c& mix A) or inositol 1,4,5-trisphosphate (InsP3; mix B). Overall, 52% of biopsies produced one or more odorant-responsive olfactory neurons, whereas 24% of all olfactory neurons tested responded to odorant exposure with a change in [Ca2+]i. As in olfactory neurons from other species, the data suggest that odorant exposure elicited calcium influx via second-messenger pathways involving cAMP or InsP3. Unlike olfactory neurons from other species that have been tested...
We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulat... more We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in 2 age groups of younger (≤ 45 years) and older (≥ 60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to 2 odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects' absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in peripheral cellular specificity may impact odor discrimination and olfactory adaptation in the elderly. It is also possible that chronic adaptation as a result of reduced specificity contributes to observed declines in absolute sensitivity.
Protein kinases A and C have been postulated to exert multiple effects on different elements of s... more Protein kinases A and C have been postulated to exert multiple effects on different elements of signal transduction pathways in olfactory receptor neurons. However, little is known about the modulation of olfactory responses by protein kinases in intact olfactory receptor neurons. To further elucidate the details of the modulation of odorant responsiveness by these protein kinases, we investigated the action of two protein kinase inhibitors: H89, an inhibitor of protein kinase A, and N-myristoylated EGF receptor, an inhibitor of protein kinase C, on odorant responsiveness in intact olfactory neurons. We isolated individual olfactory neurons from the adult human and rat olfactory epithelium and measured responses of the isolated cells to odorants or biochemical activators that have been shown to initiate cyclic AMP or inositol 1,4,5-trisphospate production in biochemical preparations. We employed calcium imaging techniques to measure odor-elicited changes in intracellular calcium that occur over several seconds. In human olfactory receptor neurons, the protein kinase A and C inhibitors affected the responses to different sets of odorants. In rats, however, the protein kinase C inhibitor affected responses to all odorants, while the protein kinase A inhibitor had no effect. In both species, the effect of inhibition of protein kinases was to enhance the elevation and block termination of intracellular calcium levels elicited by odorants. Our results show that protein kinases A and C may modulate odorant responses of olfactory neurons by regulating calcium fluxes that occur several seconds after odorant stimulation. The effects of protein kinase C inhibition are different in rat and human olfactory neurons, indicating that species differences are an important consideration when applying data from animal studies to apply to humans.
Acceptance of and expressed preference for varying levels of salt (NaCl) were assessed among chil... more Acceptance of and expressed preference for varying levels of salt (NaCl) were assessed among children 3-6 years of age. 20 children received 0, 0.17, and 0.34 M NaCl in aqueous solution, and 20 received these same NaCl concentrations in a soup broth. In both groups, children were asked to ingest as much as they wanted to each stimulus during brief, sequential presentations and to indicate which stimulus they preferred in a series of paired-comparison presentations. A striking, context-specific reaction to the taste of salt was observed on both measures. Children in this age group strongly rejected even the moderate level of salt in water relative to unsalted water. In contrast, the most highly salted soup was well accepted and preferred to either unsalted or moderately salted soup by the majority of children.
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Papers by Beverly Cowart