Dual capacity of a human olfactory receptor.
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Adult↗
Biomedical subjects
Thomas Hummel
Publications and source records attributed to Thomas Hummel.
Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies.
Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the developing mushroom body (MB). This correlates with the precise spatiotemporal pattern of Dscam protein expression. We demonstrate that MB neurons express different arrays of Dscam isoforms and that single MB neurons express multiple isoforms. Two different Dscam isoforms differing in their extracellular domains introduced as transgenes into single mutant cells partially rescued the mutant phenotype. Expression of one isoform of Dscam in a cohort of MB neurons induced dominant phenotypes, while expression of a single isoform in a single cell did not. We propose that different extracellular domains of Dscam share a common function and that differences in isoforms expressed on the surface of neighboring axons influence interactions between them.
Alternative Splicing↗
Responsiveness of human nasal mucosa to trigeminal stimuli depends on the site of stimulation.
There is evidence that functionally different areas can be distinguished within the nasal mucosa with regard to stimulation site and stimulus properties. The aim of the present study was the comparison of electrophysiological and psychophysical measures obtained in response to mechanical and chemosomatosensory stimulation of two different regions of the nasal mucosa. A total of 40 volunteers participated in this study (age range 21-36 years). Chemosomatosensory event-related potentials (ERPs) were recorded using gaseous CO2 as stimulant, while somatosensory ERPs were recorded in response to intranasal mechanical stimuli (air puffs). Stimuli were released to the anterior portion and to the posterior portion of the nasal cavity. A significant interaction between stimulus properties and site of stimulation could be detected after analysis of ERP parameters and intensity ratings. Thus, the chemosensory stimulus was perceived as stronger in the anterior portion of the nasal cavity whereas this was not the case for mechanosensory stimuli. In addition, mechanosensory stimuli were found to evoke ERPs with shorter latencies. These results underline the idea that the respiratory mucosa should not be seen as a homogeneous tissue. It exhibits varying sensitivities to trigeminal stimulation depending on stimulus quality and site of stimulation. Hence, perception of chemosensory stimuli seems to be most accurate in the anterior portion of the nasal cavity, while sensitivity to mechanical stimuli appears to be highest in the posterior portion. In addition, these differences within the respiratory mucosa may contribute to differences in the perception of orthonasal and retronasal odorous stimulation.
Adult↗
Olfactory dysfunction and daily life.
The objective of the present study was to investigate the hypothesis that subjects with parosmia suffer more in their daily life than patients who experience only quantitative olfactory loss. Two hundred five outpatients of the Smell and Taste Clinic and 25 healthy controls were included. The newly developed Questionnaire of Olfactory Disorders (QOD) was administered in combination with other psychometric tests (Beck Depression Inventory, "Befindlichkeitsskala" and the Short Form-36 Health Survey) along with an olfactory test ("Sniffin' Sticks"). Results of the QOD were found to be an appropriate and valid measure of the impact of olfactory dysfunction on daily life. Patients with parosmia and quantitative olfactory dysfunction show higher rates of daily life complaints when compared to patients suffering from quantitative olfactory impairment only (QOD-PS: P=0.005). In addition, hyposmic and anosmic patients indicated significantly more complaints compared to patients with normosmia. Further, female patients seemed to suffer more from olfactory dysfunction than male patients. In conclusion, the assessment of the degree of qualitative olfactory dysfunction may be possible by the use of instruments based on questionnaires regarding daily life problems.
Adult↗
Afferent induction of olfactory glomeruli requires N-cadherin.
Drosophila olfactory receptor neurons (ORNs) elaborate a precise internal representation of the external olfactory world in the antennal lobe (AL), a structure analagous to the vertebrate olfactory bulb. ORNs expressing the same odorant receptor innervate common targets in a highly organized neuropilar structure inside the AL, the glomerulus. During normal development, ORNs target to specific regions of the AL and segregate into subclass-specific aggregates called protoglomeruli prior to extensive intermingling with target dendrites to form mature glomeruli. Using a panel of ORN subclass-specific markers, we demonstrate that in the adult AL, N-cadherin (N-cad) mutant ORN terminals remain segregated from dendrites of target neurons. N-cad plays a crucial role in protoglomerulus formation but is largely dispensible for targeting to the appropriate region of the AL. We propose that N-cad, a homophilic cell adhesion molecule, acts in a permissive fashion to promote subclass-specific sorting of ORN axon terminals into protoglomeruli.
Animals↗
Detection of presymptomatic Parkinson's disease: combining smell tests, transcranial sonography, and SPECT.
Olfactory loss is among the early signs of Parkinson's disease (PD). We investigated whether "idiopathic" olfactory dysfunction might relate to signs of nigral degeneration. Olfactory tests were combined with transcranial sonography of the substantia nigra and single photon emission computed tomography (SPECT) imaging. Thirty patients diagnosed with idiopathic olfactory loss participated. Eleven of these patients exhibited an increased echogenicity of the SN in the transcranial sonography. In 10 of these 11 patients, SPECT scans with (123)I-FP-CIT were performed. Median uptake ratios in the basal ganglia were pathological in 5 patients, 2 patients exhibited borderline findings, and 3 patients had normal results. Considering patients with idiopathic olfactory dysfunction, noninvasive transcranial sonography seems to be helpful in identifying patients potentially at risk to develop PD. Longitudinal follow-up studies are necessary to estimate the ratio of patients with dopaminergic cell loss in the basal ganglia who will develop PD in the future.
Adult↗
Early enteral gut feeding with conditionally indispensable pharmaconutrients is metabolically safe and is well tolerated in postoperative cancer patients--a pilot study.
BACKGROUND & AIMS: Postoperative early enteral gut feeding with conditionally indispensable pharmaconutrients can contribute to minimize trauma-induced gut damage. Aim of this pilot study was the evaluation of metabolic effects and gastrointestinal tolerance of a new enteral supplement. METHODS: In a prospective open clinical trial, 20 cancer patients received the test supplement containing glutamine (as dipeptides), antioxidative (pro-)vitamins (C, E, beta-carotene), maltodextrine, tributyrine, sodium, zinc, and selenium within 2-3 h after elective gastrointestinal surgery continuously via jejunostomy tube for 3 postoperative days (500 ml/day). From postoperative day 3-5, additional enteral nutrition (1500 kcal/6270 kJ/day) was given. Metabolic effects (substrate monitoring, hematology, liver/kidney parameters) and tolerance (nausea, vomiting, flatulence, constipation, diarrhea) was assessed through the study. RESULTS: Gastrointestinal tolerance of the supplement was excellent: no adverse events related to the product were documented. Significantly increased mean plasma levels (day 3 vs. day 1) of vitamin C (13.0 +/- 7.3 vs. 62.8 +/- 29.7 micromol/l), vitamin E (13.5 +/- 6.6 vs. 20.8 +/- 9.2 micromol/l), zinc (5.6 +/- 1.9 vs. 8.6 +/- 2.3 micromol/l) and selenium (35.0 +/- 19.6 vs. 42.9 +/- 0.9 microg/l) as well as enhanced plasma glutamine levels (429.6 +/- 90.6 vs. 530 +/- 200.1 micromol/l) reflected an effective absorption of substrates supplied. Adverse effects on organ functions and hematology were not observed. CONCLUSIONS: Early postoperative gut feeding with the newly developed enteral supplement shows no adverse effects, is well tolerated in cancer patients and provides a novel method to deliver conditionally indispensable pharmaconutrients.
Aged↗
Olfaction in the fetal and premature infant: functional status and clinical implications.
This article considers olfaction as a functioning source of information for the fetus and the neonate, born on term or prematurely. It aims to present how odors are involved in the sensory continuity between the prenatal and postnatal environments and how they influence the earliest adaptive responses of newborns in the realms of self-regulation, emotional balance, feeding, and social interactions.Finally, it evaluates odors as sensory means to ameliorate the physiologic and behavioral responses of preterm infants to the adverse impacts of separation from mother, nonoral feeding, or iatrogenic distress.
Embryonic and Fetal Development↗
A new method for comparing orthonasal and retronasal olfaction.
Odors seem to be perceived differently when presented ortho- or retronasally. In this study, stimuli of controlled concentration and duration were applied in either the anterior nasal cavity or epipharynx by means of air-dilution olfactometry. Stimulus concentration was monitored in the olfactory cleft. In Experiment 1, odor thresholds to a food (chocolate) and a nonfood (lavender) odor were lower for orthonasal, compared with retronasal, stimulation. In Experiment 2, intensity ratings to suprathreshold odor concentrations were significantly higher for orthonasal than for retronasal stimulation with hydro- hydrogen sulfide, but not phenyl ethyl alcohol. Accordingly, amplitudes and latencies of olfactory event-related gen potentials to retronasal stimuli were found to be smaller and prolonged, respectively. This indicates differential processing of olfactory stimuli presented through the retronasal or orthonasal routes. )
Adult↗
The influence of training on chemosensory event-related potentials and interactions between the olfactory and trigeminal systems.
It is not possible to accurately predict the perceptual response to odorants and odorant mixtures without understanding patterns of suppression and facilitation that result from interactions between the olfactory and trigeminal systems. The current study extends previous findings by exploring the effect of intensive training on the interaction between these systems and also by using a different mixed chemosensory stimulus to examine whether the principles established in earlier studies generalize to different odorants. Stimuli were chosen so as to selectively activate the olfactory (H2S) and trigeminal (CO2) nerves. In addition, linalool was included as a stimulus that activated both systems. Thirty-five participants (19 men, 16 women) rated the intensity of each stimulus when presented both alone and in binary mixtures (linalool + H2S, and linalool + CO2). Chemosensory event-related potentials were obtained from three recording positions. Analysis of intensity ratings showed that linalool was significantly less intense than the other stimuli when presented alone. In binary mixtures, H2S was strongly suppressed by linalool. One week of intensive odor training produced significant and specific reductions in the intensity of linalool and H2S, both alone and in their mixture. Training with a different odor (champignol) had no effect. Chemosensory event-related potential data confirmed previous findings showing changes in topographical distribution that reflected the degree of trigeminal activity. Binary mixtures generally produced larger amplitudes than single stimuli. Latencies clearly differentiated between the three single stimuli and the binary mixtures. Changes were observed in event-related potentials that reflected those obtained for intensity ratings in that they were observed for linalool and H2S in the linalool trained group only. The amplitude of the late 'endogenous' component (P3) was significantly decreased for these odors at frontal recording sites. In summary, strong and specific training effects were observed in intensity ratings for participants trained with the test odor (linalool), but not for those trained with a different odor. This was supported by a significant decrease of amplitudes of the event-related potentials at frontal recording sites following training with the test odor only
Acyclic Monoterpenes↗
A simple and reliable method for clinical assessment of odor thresholds.
We investigated whether presenting of dilutions of phenyl ethyl alcohol at random succession according to the method of constant stimuli can replace the standard procedure of presenting a various number of dilutions in a staircase paradigm. Forty-six men and 44 women, aged 19-76 years, participated in this study. Phenyl ethyl alcohol was diluted in a ratio of 1:2, starting from 4%. Presentation of the odorant followed a three-alternative, temporal forced-choice paradigm with two blanks in addition to the odorant. Twenty dilutions were administered in a randomized order. Odor threshold was obtained by logistic regression of the correct and incorrect identifications of the probe containing the odorant. Thresholds were also calculated on the basis of the first 16 dilution steps only. Results from these procedures were compared with 'gold-standard' threshold assessment employing a three-alternative, temporal forced-choice staircase paradigm with seven reversals using 16 dilutions of phenyl ethyl alcohol. The method of constant stimuli took a shorter and less variable testing time than the staircase technique. The use of 20 dilution steps provided no better results than the use of 16 steps. The method of constant stimuli exhibited a good test-retest reliability (r = 0.7; P < 0.001) comparable to that of the staircase method and provided unbiased results highly correlated (r = 0.8; P < 0.001) with those of the staircase technique with similar inter-test variability. Applying 16 dilutions (1:2 steps) of phenyl ethyl alcohol at random succession in a three-alternative, temporal forced-choice paradigm is thus a simple and reliable procedure for the reproducible assessment of odor thresholds that may be contemplated as an alternative to the 'gold-standard' staircase method of clinical odor threshold assessment.
Adult↗
[Testing the sense of smell using validated procedures].
There is a growing interest into the investigation of smell disorders in both research and clinical practice. For psychophysical ("subjective") investigations related to the sense of smell a variety of test kits are available, namely the various "Sniffin' Sticks" kits, the UPSIT (University of Pennsylvania Smell Identification Test) or the CCSIT (Cross-Cultural Smell Identification Test). Recording of olfactory evoked potentials (OEPs) and respiration olfactometry can be used for diagnosing smell dysfunctions in a more objective way.
Humans↗
[Testing the sense of taste using validated procedures].
Psychophysical tests related to the sense of taste are usually less complex than those of the sense of smell. In addition to global tests a regional examination of the sense of taste might be indicated to search for nerve lesions. There are numerous validated psychophysical tests available based on the administration of liquid or solid substrates. The use of electrical currents (electrogustometry) is especially feasible for a rapid regional testing. The registration of gustatory event-related potentials to objectify results from psychophysical examination is possible although limited to a few centers world-wide.
Electrophysiology↗
Age-related decline of intranasal trigeminal sensitivity: is it a peripheral event?
Compared to younger subjects, older people have a reduced sensitivity of the intranasal trigeminal system which responds to irritation of the nasal cavity. It is unclear whether the cause of this difference relates to age-dependent changes in the periphery of the system. The aim of the present study was the comparison of intranasal trigeminal thresholds assessed through electrophysiological measurements in eight young (four women, four men; mean age 25 years) and eight older subjects (four women, four men; mean age 62 years). The negative mucosa potential (NMP), a peripheral correlate of trigeminal activation, was recorded from the nasal mucosa in response to stimulation with varying concentrations of the mixed olfactory/trigeminal stimulants menthol and linalool. Thresholds were estimated as the strongest concentration which did not elicit a NMP response. Older subjects were found to have higher thresholds for menthol when compared to younger subjects. Furthermore, an explorative analysis indicated that the increase of response amplitudes to increasing stimulus concentrations was shallower in older subjects. These findings indicate that age related loss of intranasal trigeminal sensitivity seems to take place, at least to some degree, in the periphery of the intranasal trigeminal system.
Acyclic Monoterpenes↗
Depth of olfactory sulcus and olfactory function.
The aim of this study was to identify whether the depth of the olfactory sulcus relates to olfactory function in healthy subjects. Forty-four healthy, male volunteers (age range 22-45 years, mean age 28.3 years) were included in this study. Olfactory function was measured for phenyl ethyl alcohol odor thresholds, odor discrimination, and odor identification. Magnetic resonance imaging of the olfactory sulcus was performed immediately following olfactometry. Based on previous investigations the depth of the olfactory sulcus was measured in the plane of the posterior tangent through the eyeballs. Olfactory function correlated significantly with left-sided depth of the olfactory sulcus (r(44)=0.33, P=0.03); no such correlation was seen for the right side. In addition, olfactory sulcus depth was found to be significantly deeper on the right compared to the left side (t=5.61, P<0.001). The present results suggest that there is small, but significant relation between morphological brain structures and measures of olfactory function. Further, lateralization of olfactory sulcus depth may correlate to functional lateralization in the olfactory system. Thus, it may be carefully speculated that sensory input in the olfactory system results in cortical growth in the area of the olfactory sulcus, at least at some developmental stage.
Adult↗
Effects of olfactory function, age, and gender on trigeminally mediated sensations: a study based on the lateralization of chemosensory stimuli.
The present investigation aimed to compare trigeminal nasal function of anosmic and hyposmic patients to healthy controls. Further, we aimed to study effects of age and gender on trigeminally mediated sensations following intranasal chemosensory stimulation. Participants were 35 patients with olfactory dysfunction (n=13: functional anosmia; n=22: hyposmia; age 28-69 years, mean age 56 years). Their results were compared with 17 normosmic subjects (28-82 years, mean 52 years). To analyze effects of age and gender in healthy subjects, an additional 24 healthy subjects were included (19-27 years; mean 24 years). Olfactory function was assessed using the 'Sniffin' Sticks' test kit (butanol odor threshold, odor discrimination, odor identification). The subjects' ability to lateralize odors was investigated for benzaldehyde and eucalyptol. Patients with olfactory dysfunction had lower scores in the lateralization task than controls (P<0.001) indicating decreased trigeminal sensitivity. Among anosmic patients scores were not different in relation to different causes of olfactory dysfunction (P>0.29). There was a weak, but significant, correlation between localization of eucalyptol and duration of olfactory dysfunction (P=0.017). When investigating normosmic subjects only, no gender-related difference was apparent for lateralization scores. However, older subjects had lower scores than younger ones (P<0.01). Results of partial correlational analyses controlling for age suggested a relation between the trigeminal and the olfactory systems. In conclusion, results of the present study indicate that patients with olfactory dysfunction have lower trigeminal sensitivity compared with normosmic controls. This seems to be independent of the cause of olfactory loss. The deficit appears to improve with duration of the olfactory dysfunction, possibly indicating adaptive mechanisms. Further, the data suggest an age-related decrease of intranasal trigeminal sensitivity in healthy subjects. Analyses additionally indicate a correlation between olfactory and trigeminal sensitivity.
Adult↗
Axonal targeting of olfactory receptor neurons in Drosophila is controlled by Dscam.
Different classes of olfactory receptor neurons (ORNs) in Drosophila innervate distinct targets, or glomeruli, in the antennal lobe of the brain. Here we demonstrate that specific ORN classes require the cell surface protein Dscam (Down Syndrome Cell Adhesion Molecule) to synapse in the correct glomeruli. Dscam mutant ORNs frequently terminated in ectopic sites both within and outside the antennal lobe. The morphology of Dscam mutant axon terminals in either ectopic or cognate targets was abnormal. Target specificity for other ORNs was not altered in Dscam mutants, suggesting that different ORNs use different strategies to regulate wiring. Multiple forms of Dscam RNA were detected in the developing antenna, and Dscam protein was localized to developing ORN axons. We propose a role for Dscam protein diversity in regulating ORN target specificity.
Alleles↗
Neurological aspects of taste disorders.
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Humans↗