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Biomedical subjects

M M Mozell

Publications and source records attributed to M M Mozell.

At least 19 recordsLinked to original sources

Mucosal activity patterns as a basis for olfactory discrimination: comparing behavior and optical recordings.

In over half a century numerous studies have demonstrated that different odorants produce individually different spatial patterns of neural receptor activity on the olfactory mucosa. However, the thought that these differential activity patterns could be the neural code underlying olfactory perception has not been tested directly. In the present study using operant techniques, rats were trained to differentially identify five odors from a homologous series of iso-intensive straight-chain aldehydes that differed serially by only one carbon atom, viz. hexaldehyde to decaldehyde. The rats identified each of the five odorants with greater than 90% correct identification. The degree of perceptual similarity between any pair of the five odorants was determined. Using multidimensional scaling techniques (MDS) the similarity measures yielded a two-dimensional perceptual odorant space. Optical techniques were used to record the olfactory mucosal activity patterns in response to these same five iso-intensive aldehydes. The mucosal activity elicited by each odorant revealed individually distinct band-like patterns that varied both within and across these bands. More importantly, the relative differential responsivity of the bands was related to chain length. An MDS analysis of the dissimilarity measure between all possible pairs of odorant induced activity patterns yielded a two-dimensional neurophysiologic odorant space. Further analysis indicated that the neurophysiologic and psychophysically determined odorant spaces were highly correlated (F(1,39)=23.9, P=nil). These results give additional credence to the concept that the odorant-induced mucosal activity patterns may serve as the substrate for the perception of odorant quality.

Aldehydes↗

AChemS: the beginning. Association for Chemoreception Sciences.

This paper unfolds the events, the people and the times that led up to the founding of AChemS and fashioned its character during its early formative years. It describes the path over which AChemS came, going from the original assertions and denials for the need of such an organization to its later inception and nascent development. This narration highlights such topics as the debate over the need for AChemS, the role of National Science Foundation in the founding of AChemS, the derivation of the Association's name, the choice of Sarasota and the Hyatt House as the meeting site, the generation of the programs for the early annual meetings, the adoption of the bylaws, the process of incorporation and tax deferment, and the birth of the Givaudan Lectureship. Most emphatically highlighted, however, is the enthusiasm, commitment and hard work that the members of the chemosensory research community displayed in bringing AChemS to fruition.

Congresses as Topic↗

A numerical model of nasal odorant transport for the analysis of human olfaction.

The transport and uptake of inspired odorant molecules in the human nasal cavity were determined using an anatomically correct three-dimensional finite element model. The steady-state equations of motion and continuity were first solved to determine laminar flow patterns of odorous air at quiet breathing flow rates. The air stream entering the ventral tip of the naris traveled to the olfactory slit, and then passed through the slit in nearly a straight path without forming separated recirculating zones. The fraction of volumetric flow passing through the olfactory airway was about 10%, and remained nearly constant with variation in flow rate. The three-dimensional inspiratory velocity field was used in the solution of the uncoupled steady convective-diffusion equation to determine the concentration field in the airways and odorant mass flux at the nasal walls. The mass-transfer boundary condition used at the nasal cavity wall included the effects of solubility and diffusivity of odorants in the mucosal lining, and the thickness of the mucus layer. The total olfactory flux of odorants, that is highly correlated with perceived odor intensity, was determined as a function of all transport parameters in our model. Increase in nasal flow rate at a constant inlet concentration resulted in an increase in total olfactory uptake for all odorants. However, with increase in flow rate, the fractional uptake, i.e., total olfactory flux normalized by convective flux at the inlet, decreased for poorly soluble odorants, while it increased for highly soluble odorants. The pattern of flux (or imposed patterning) across the olfactory mucosa, that carries information concerning odor identity, was also determined as a function of transport parameters. There was an overall decrease in odorant flux as the location on the olfactory surface was varied from the anterior towards the posterior and from the inferior towards the superior ends. The flux pattern became more uniform, i.e., the steepness of the flux gradients across the olfactory surface decreased, as the mucus solubility of the odorants decreased. Different odorants generated discernibly different flux patterns across the olfactory mucosa that may contribute to the encoding of odor quality. Variation of total olfactory flux with time after cessation of airflow was determined by solving the unsteady diffusion equation in the air-phase. The flux decreased approximately exponentially with time. The rate of decay decreased as solubility and diffusivity decreased, but was very rapid over a wide range of the parameters, with time constants of less than 0.5 s for most odorants, implying a rapid decrease in perceived odor intensity with cessation of nasal airflow.

Absorption↗

Effect of nasal dilators on perceived odor intensity.

Subjects wearing nasal dilators rated olfactory stimuli as being more intense compared with ratings done without nasal expansion. The results support a perceptual constancy model in olfaction.

Administration, Intranasal↗

The interaction of imposed and inherent olfactory mucosal activity patterns and their composite representation in a mammalian species using voltage-sensitive dyes.

From amphibian data, two mechanisms that could underlie the encoding of odorants by the mucosal activity patterns they engender are as follows (1) receptors with similar odorant selectivities could be aggregated spatially on the mucosa (inherent patterns); (2) in analogy to gas chromatography, as odorants are drawn along the surface of the mucosa the strongly sorbed ones could be deposited preferentially upstream, whereas the weakly sorbed ones could be distributed more evenly (imposed patterns). Do both of these possible coding mechanisms operate in mammals and, if so, how do they interact in giving composite patterns (imposed + inherent)? Fluorescence changes in di-4-ANEPPS applied to rat mucosas were monitored by a 10 x 10 pixel photodiode array. To observe the inherent patterns, three odorants of varying sorbabilities first were puffed uniformly onto the entire mucosa mounted in a Delrin chamber. To bring out the imposed patterns, the chamber was then sealed to replicate anatomically the rat's nasal cavity, and these same odorants were drawn at three flow rates along the mucosal flow path. The results demonstrated for the first time the existence of imposed patterns in a mammal. The strongly sorbed odorants, unlike the weakly sorbed one, showed marked imposed patterns. Within physiological limits, increasing the flow rate decreased the magnitude of the imposed patterns. One might consider strategies that the olfactory process could use either to negate or to take advantage of the chromatographic effect, because the lability of the composite patterns with changing stimulus conditions raises questions about their role in odorant encoding.

Animals↗

Numerical simulation of airflow in the human nasal cavity.

An anatomically correct finite element mesh of the right human nasal cavity was constructed from CAT scans of a healthy adult nose. The steady-state Navier-Stokes and continuity equations were solved numerically to determine the laminar airflow patterns in the nasal cavity at quiet breathing flow rates. In the main nasal passages, the highest inspiratory air speed occurred along the nasal floor (below the inferior turbinate), and a second lower peak occurred in the middle of the airway (between the inferior and middle turbinates and the septum). Nearly 30 percent of the inspired volumetric flow passed below the inferior turbinate and about 10 percent passed through the olfactory airway. Secondary flows were induced by curvature and rapid changes in cross-sectional area of the airways, but the secondary velocities were small in comparison with the axial velocity through most of the main nasal passages. The flow patterns changed very little as total half-nasal flow rate varied between resting breathing rates of 125 m/s and 200 ml/s. During expiration, the peaks in velocity were smaller than inspiration, and the flow was more uniform in the turbinate region. Inspiratory streamline patterns in the model were determined by introducing neutrally buoyant point particles at various locations on the external naris plane, and tracking their path based on the computed flow field. Only the stream from the ventral tip of the naris reached the olfactory airway. The numerically computed velocity field was compared with the experimentally measured velocity field in a large scale (20x) physical model, which was built by scaling up from the same CAT scans. The numerical results showed good agreement with the experimental measurements at different locations in the airways, and confirmed that at resting breathing flow rates, airflow through the nasal cavity is laminar.

Adult↗

A mass transport model of olfaction.

A theoretical model of olfaction involving all the major mechanisms in the mass transport of odorant molecules from inspired air to the olfactory receptors is developed. The mechanisms included are: (i) convective bulk flow of odorant molecules to the olfactory region of the nasal cavity by inhaled air, (ii) lateral transport of odorant molecules from the flowing gas stream in the olfactory region onto the olfactory mucus surface, (iii) sorption of odorant molecules into the mucus at the air-mucus interface, (iv) diffusion of odorant molecules through the mucus layer, and (v) interaction of odorant molecules with the olfactory receptor cells. The model is solved to yield the olfactory response as a function of various physical variables such as the inspiratory flow rate, the mass transfer coefficient, the initial concentration of odorant molecules in the inhaled air, the length of the olfactory mucosa, the thickness of the olfactory mucosa, and the air-mucus partitioning (or solubility in the mucus) of odorant molecules. It was determined that the flow rate of the odorant carrier gas, length of the olfactory mucus surface, and the solubility of odorant molecules in the olfactory mucus should play important roles in determining the odor intensity for these odorants. The model predicts that, given adequate mucus surface for sorption, increase in the flow rate results in an increase in perceived odor intensity for the readily sorbed or highly soluble odorants (such as carvone) and a decrease in odor intensity for the poorly sorbed or insoluble odorants (such as octane). With a substantial decrease in the mucus surface for sorption, increase in the flow rate results in a decrease in perceived odor intensity for all odorants. The theoretical results show good agreement with various experimental data obtained from both psychophysical and electrophysiological studies of olfaction using animals and human subjects.

Absorption↗

Velocity profiles measured for airflow through a large-scale model of the human nasal cavity.

An anatomically accurate, x20 enlarged scale model of a healthy right human adult nasal cavity was constructed from computerized axial tomography scans for the study of nasal airflow patterns. Detailed velocity profiles for inspiratory and expiratory flow through the model and turbulence intensity were measured with a hot-film anemometer probe with 1 mm spatial resolution. Steady flow rates equivalent to 1,100, 560, and 180 ml/s through one side of the real human nose were studied. Airflows were determined to be moderately turbulent, but changes in the velocity profiles between the highest and lowest flow rates suggest that for normal breathing laminar flow may be present in much of the nasal cavity. The velocity measurements closest to the model wall were estimated to be inside the laminar sublayer, such that the slopes of the velocity profiles are reasonably good estimates of the velocity gradients at the walls. The overall longitudinal pressure drop inside the nasal cavity for the three inspiratory flow rates was estimated from the average total shear stress measured at the central nasal wall and showed good agreement with literature values measured in human subjects.

Adult↗

The recording of odorant-induced mucosal activity patterns with a voltage-sensitive dye.

1. Fluorescence changes in the dye (WW 781) were monitored at 100 contiguous sites in a 10 x 10-pixel array on the bullfrog and salamander olfactory mucosas every 10 ms in response to odorous stimuli. The odorants were d-limonene, butanol, and amyl acetate, each presented at two concentrations with a 3:1 ratio. 2. The fluorescence signals elicited by these odorous stimuli were nearly identical in shape and time course to the electro-olfactograms (EOGs) recorded from the same animal under identical conditions. Like the EOGs, the fluorescence signals exhibited adaptation and were abolished by both Triton X-100 and ether. There was no measurable fluorescence when the tissue was not stained with the dye, and there was no change in fluorescence when, for stained tissue, nonodorized, humidified air was presented as the stimulus. 3. This technique presumably monitors the same events as the EOG, but has the advantage of simultaneously recording the odorant-induced activity from multiple sites across most of the mucosa. Thus this technique preserves subtle differences heretofore lost by other techniques both in the coarseness of their matrices and in the variability generated by trying to piece together, into one collage, results from numerous presentations given at different times. 4. In all preparations, there was a larger difference in the inherent activity patterns (derived from response magnitudes) between different odorants than between different concentrations of the same odorant. These differences were largest on the mucosa lining the floor of salamander's olfactory sac. d-limonene and butanol gave their largest responses near the internal and external nares, respectively, whereas the responses for amyl acetate were more uniform across the mucosal sheet. In contrast to the salamander, smaller differences were observed for both the roof and the floor of the bullfrog's olfactory sac. For the floor, both amyl acetate and d-limonene elicited similar patterns of response magnitude, whereas butanol differed from each of these odorants by eliciting a larger response on the anteriolateral aspect of the mucosa and a lesser response on the remainder. For the roof, different odorants produced different activity patterns, which had profiles not simply described as regions of maximal and minimal responsiveness. 5. Different inherent activity patterns based on temporal characteristics of the fluorescence responses were also observed for different odorants. Each odorant produced a different pixel-by-pixel pattern for the times at which the responses started and ended. For any given odorant, these temporal patterns paralleled the patterns given by response magnitudes.(ABSTRACT TRUNCATED AT 400 WORDS)

Ambystoma↗

Successful treatment of phantosmia with preservation of olfaction.

A 26-year-old woman had an 8-year history of phantosmia in her left nostril. The phantosmia could be eliminated by nostril occlusion or cocainization of the olfactory epithelium on the involved side. Because her symptoms and testing suggested a peripheral problem, a full-thickness "plug" of olfactory epithelium from under the cribriform plate (including all the fila olfactoria) was excised. At 5 weeks postoperatively, the phantosmia was completely gone, and her olfactory ability had returned to preoperative levels. Either the removal of abnormal peripheral olfactory neurons from the nose or the interruption of incoming signals to the olfactory bulb eliminated the phantosmia. This form of therapy for phantosmia offers an alternative to more radical procedures such as olfactory bulbectomy and may offer a significant sparing of olfactory ability.

Adult↗

Determination of carbon dioxide detection thresholds in trained rats.

Concentration-response functions for the detection of CO2 were established for six rats. The animals were tested in a wind tunnel apparatus and trained using standard operant techniques and a discrete trials, go, no-go successive discrimination paradigm. The primary conclusion to be drawn from the performance measurements is that, at least under carefully controlled conditions, rats can detect physiologic concentrations of CO2 (0-4%). Minimum detectable concentrations fell within the range of 0.04-1.7% CO2. The concentration-response function describing the detectability of CO2 for the six rats was divided into an upper and lower limb at a concentration (5%) that was approximately equal to the end expiratory CO2 levels for the rat (4.88%). High levels of performance were observed for concentrations above this point, while those below it (0.02-2.5%) represented the dynamic range of detectability. Based on a 65% performance criterion, the average threshold performance for six rats was 0.52%. Possible interpretations of these data are discussed.

Animals↗

Odorant identification in rats: an update.

In a previous report, Youngentob et al. (8) described a new and substantially different type of animal psychophysical procedure in which rats were trained to differentially report (i.e., identify) five different odorants. The present study confirms and extends the usefulness of the cross-modal association paradigm as an effective means for developing an extensive nonverbal "vocabulary" with which an animal can communicate multiple changes in sensory stimuli. Given the appropriate nonverbal means of communication, a rat has the channel capacity to differentially report (i.e., identify), at least ten different odorants. The expansion to a ten odorant identification task is discussed with respect to the analytic capabilities of the animal model for the study of olfactory quality perception.

Algorithms↗

Fish-odor syndrome presenting as dysosmia.

We describe a patient who had perceived an unpleasant odor or taste for at least 20 years. Several other physicians had unsuccessfully treated her for infections, mucus membrane dryness and inflammation, chronic tonsillitis, and psychiatric disorders. Her workup at the State University of New York Health Science Center at Syracuse Olfactory Referral Center included a thorough history, examinations (including endoscopic studies of her nose, pharynx, and lungs), roentgenograms, taste testing, olfactory testing, and selective anesthesia of her chemosensory areas. The perception occurred only during exhalation, and appeared to be binasal. These findings, together with her morning mucus sample having a strong fishlike odor, prompted us to suspect a metabolic problem. Further testing at the Monell-Jefferson Chemosensory Clinical Research Center, Philadelphia, Pa, confirmed that she had trimethylaminuria. It is important to consider this and other treatable conditions when evaluating individuals with olfactory complaints.

Adult↗

A method for establishing a five odorant identification confusion matrix task in rats.

Using a cross-modal association paradigm, rats were trained to associate a particular tunnel and response location with one of five different odorants (isoamyl acetate, propyl acetate, acetic acid, phenethyl alcohol, and anethole). Each of the five tunnels differed with respect to: 1) the illuminated pattern on the response key; 2) the brightness of the illuminated pattern; and 3) the somesthetic quality of the tunnel floor. Standard operant techniques were used to train trial initiating and sampling behavior at a central odorant presentation point. Following acquisition training, the animals were tested using a standard 5 X 5 confusion matrix design. The results showed for the first time that rats are capable of performing, with a high degree of accuracy, an odorant identification confusion matrix task analogous to humans. Furthermore, using multidimensional scaling techniques, these data represent the first instance in which the perceptual odor space of an animal can be determined. With the animal model in hand, we can begin to examine how, in the presence of neural dysfunction, one odorant may be correctly identified as another.

Animals↗

The biophysics of nasal airflow.

The biophysics of nasal airflow involve the measurement, analysis, and understanding of bulk airflow or momentum transport through the nasal cavity and of the exchange of mass and heat laterally between the air stream and the walls. In both of these areas, optimal progress depends on judicious, combined, and continuous use of physical models, mathematical calculations, and measurements made on human subjects. The progress that has been made to date is both fascinating and encouraging and suggests that great improvement in understanding, diagnosis, and treatment of nasal and upper airway disease will be possible in the future through closer contact and cooperation between clinicians and physical and biological scientists.

Airway Resistance↗

Olfactory mucosa/air partitioning of odorants.

The present study evaluates the contribution of the receptor cell compartment to the total mucosal odorant uptake. Using radioactive odorants, partition coefficients for normal bullfrog olfactory mucosa were compared to the partition coefficients from mucosa in which the receptor cells had been removed by cutting one of the olfactory nerves and allowing two weeks for complete degeneration. For the more water-soluble odorants (butanol and isobutyric acid), both sides sorbed the same amount of odorant, suggesting that the mucosal uptake mostly reflects uptake by the water in the mucosa. For the less water soluble odorants (octane and amyl acetate), the uncut side did sorb significantly more odorant than the cut side.

1-Butanol↗

Airflow patterns in a human nasal model.

Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model.

Catheterization↗

A quantitative analysis of sniffing strategies in rats performing odor detection tasks.

The sniffing strategies of rats performing two learned odor detection tasks were monitored with a pneumotachograph and quantitatively analyzed with respect to fifty-two characteristics. The results of this study demonstrated that the rat's sniffing varied for different odorants, different concentrations of the same odorant, and between air and odor trials. The variations resulted from changes in such descriptors as volume, duration, average flow rate, peak flow rate and sniff number. In general, a sniffing pattern began with one or two inspirations followed by alternating inspirations and expirations. Comparison of earlier and later sniffs in a bout demonstrated a growth towards both a maximum inspiratory and expiratory sniff which had the largest duration, volume, average flow rate and peak flow rate. These maximum sniffs occurred at or near the end of a bout. Although analysis of the fifty-two characteristics was quantitatively useful in determining the physiologic values and airflow patterns generated by sniffing, a single univariate response measure incorporating twelve characteristics was the best descriptor of how sniffing patterns varied with odorant stimuli.

Animals↗