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Blood groups as genetic markers in glaucoma.

A series of 474 mixed cases of glaucoma was assessed to determine whether there were any genetic differences between different types of glaucoma. A careful distinction was made between chronic open angle glaucoma (COAG), acute and chronic angle closure glaucoma, ocular hypertension, low tension glaucoma, patients with large cup disc ratios, and various types of secondary glaucoma including pseudoexfoliation of the lens capsule, uveitic and traumatic glaucoma. Using ABO blood groups, Rhesus groups, ABH secretion or non-secretion, and phenylthiourea tasting we identified certain differences. The differences from normal were significant decrease in Rh-negative patients in chronic closed angle glaucoma (p less than 0.05), a decrease in ABH secretors in ocular hypertension (p less than 0.01), and fewer HB secretors in patients with COAG (p less than 0.02). There was a significant decrease in AH secretors and increase in HB secretors in both pseudoexfoliation with raised intraocular pressure compared with COAG (p less than 0.01) and in secondary glaucomas as a group compared with COAG (p less than 0.01). Tasters of phenylthiourea were more common in traumatic and uveitic glaucoma than in normal controls (p less than 0.05). These results suggest that secondary glaucoma develops in different subjects from COAG, while patients who develop a rise in intraocular pressure proceed to cupping and field loss if they have a certain genetic constitution. The groups of patients are too small for the differences to be of great prognostic value.

Blood Group Antigens↗

Transient hemiageusia in cerebrovascular lateral pontine lesions.

Knowledge of human central taste pathways is largely based on textbook (anatomical dissections) and animal (electrophysiology in vivo) data. It is only recently that further functional insight into human central gustatory pathways has been achieved. Magnetic resonance imaging studies, especially selective imaging of vascular, tumoral, or inflammatory lesions in humans has made this possible. However, some questions remain, particularly regarding the exact crossing site of human gustatory afferences. We present a patient with a pontine stroke after a vertebral artery thrombosis. The patient had infarctions in areas supplied by the anterior inferior cerebellar artery and showed vertical diplopia, right sided deafness, right facial palsy, and transient hemiageusia. A review of the sparse literature of central taste disorders and food preference changes after strokes with a focus on hemiageusia cases is provided. This case offers new evidence suggesting that the central gustatory pathway in humans runs ipsilaterally within the pons and crosses at a higher, probably midbrain level. In patients with central lesions, little attention has been given to taste disorders. They may often go unnoticed by the physician and/or the patient. Central lesions involving taste pathways seem to generate perceptions of quantitative taste disorders (hemiageusia or hypogeusia), in contrast to peripheral gustatory lesions that are hardly recognised as quantitative but sometimes as qualitative (dysgeusia) taste disorders by patients.

Adult↗

Taste receptors in the gastrointestinal tract III. Salty and sour taste: sensing of sodium and protons by the tongue.

Taste plays an essential role in food selection and consequently overall nutrition. Because salt taste is appetitive, humans ingest more salt than they need. Acids are the source of intrinsically aversive sour taste, but in mixtures with sweeteners they are consumed in large quantities. Recent results have provided fresh insights into transduction and sensory adaptation for the salty and sour taste modalities. The sodium-specific salt taste receptor is the epithelial sodium channel whereas a nonspecific salt taste receptor is a taste variant of the vanilloid receptor-1 nonselective cation channel, TRPV1. The proximate stimulus for sour taste is a decrease in the intracellular pH of a subset of acid-sensing taste cells, which serves as the input to separate transduction pathways for the phasic and tonic parts of the sour neural response. Adaptation to sour arises from the activation of the basolateral sodium-hydrogen exchanger isoform-1 by an increase in intracellular calcium that sustains the tonic phase of the sour taste response.

Animals↗

Calcium deprivation alters gustatory-evoked activity in the rat nucleus of the solitary tract.

Calcium-deprived rats develop a compensatory appetite for substances that contain calcium. To investigate the role of gustatory factors in calcium appetite, we recorded the extracellular activity of single neurons in the nucleus of the solitary tract of calcium-deprived and replete rats. The activity evoked by a broad array of taste stimuli was examined in 51 neurons from replete rats and 47 neurons from calcium-deprived rats. There were no differences between the groups in the responses of all neurons combined. However, neurons with sugar-oriented response profiles gave significantly larger responses to 3, 10, and 100 mM CaCl(2) in the calcium-deprived group than did corresponding cells in the replete group. This difference in taste-evoked responding may underlie an increase in the palatability of CaCl(2) and, in turn, contribute to the expression of calcium appetite.

Adaptation, Physiological↗

Effects of body weight and food intake on pleasantness ratings for a sweet stimulus.

A physiological role for pleasure has been suggested from observations that glucose loads reduced pleasantness ratings for sweet stimuli in normal weight but not in weight-reduced subjects. This hypothesis was reexamined in fasting and food-loaded, lean and obese subjects. Magnitude estimates of sweetness and pleasantness were obtained for seven sucrose concentrations. Indices of obesity including percent overweight, percent body fat, and body mass index were calculated. Pleasantness ratings of fasting subjects either increased up to a moderate concentration and then declined (type I hedonic response) or increased monotonically with concentration (type II hedonic response). Both types of response were found in lean and obese subjects. Within each weight group there appeared a negative correlation between pleasantness response and indices of obesity. Caloric loads reduced hedonic ratings of type II lean and obese subjects, but did not affect pleasantness response of type I lean and obese subjects. These findings indicate the presence of an hedonic monitor biased by body weight and caloric intake. The data suggest a physiological role for pleasure in regulating body weight at different set points in lean and obese subjects.

Adult↗

Neural representation of bitter taste in the nucleus of the solitary tract.

Based on the molecular findings that many bitter taste receptors (T2Rs) are expressed within the same receptor cells, it has been proposed that bitter taste is encoded by the activation of discrete neural elements. Here we examined how a variety of bitter stimuli are represented by neural activity in central gustatory neurons. Taste responses (spikes/s) evoked by bathing the tongue and palate with intensity-matched concentrations (in M) of 2 sugars (0.32 sucrose and 0.5 D-fructose), ethanol (40%), 4 salts (0.01 NaCl, 0.008 NaNO(3), 0.01 MgCl(2), and 0.05 KCl), 2 acids (0.003 HCl and 0.005 citric acid), and 10 bitter ligands (0.007 quinine-HCl, 0.015 denatonium benzoate, 0.003 l-cysteine, 0.001 nicotine, 0.005 strychnine-HCl, 0.04 tetraethylammonium chloride, 0.03 atropine-SO(4), 0.005 brucine-SO(4), 0.03 papaverine-HCl, and 0.009 sparteine) were recorded from 51 neurons in the nucleus of the solitary tract of anesthetized rats. Cluster analysis was used to categorize neurons into types based on responses to sucrose, NaCl, HCl, and quinine-HCl. Three groupings emerged: type S (responded optimally to sweets), type N (sodium-optimal), and type H/Q (responded robustly to bitters, acids, and salts). Multivariate analyses revealed that across-neuron patterns of response among bitter stimuli were strongly correlated. However, neural type H/Q, which was most responsive to bitter tastants, was not differentially sensitive to bitter stimuli and Na(+) salts, which rats perceive as distinct. Thus central neurons most responsive to bitter substances receive significant input from receptors that mediate other tastes, indicating that bitter stimuli are not represented by activity in specifically tuned neurons.

Action Potentials↗

Responses of single hamster parabrachial neurons to binary taste mixtures: mutual suppression between sucrose and QHCl.

1. Although taste experience typically arises from a mixture of gustatory stimuli, nearly all previous neurophysiological studies of the mammalian central gustatory system have focused on responses to single chemical stimuli. To begin to systematically examine CNS responses to taste mixtures, we recorded the extracellular activity of single third-order neurons in the hamster PbN to anterior tongue stimulation with binary mixtures of sucrose and QHCl. In experiment 1, neurons were tested with four concentrations of sucrose (0.001, 0.01, and 1.0 M) presented alone and mixed with 0.1 M QHCl. In experiment 2, neurons were tested with four concentrations of QHCl (0.00032, 0.0032, 0.032, and 0.1 M) presented alone and mixed with 1.0 M sucrose. 2. The response to each binary mixture was compared with the response to the more effective component (MEC) presented alone, and those that differed by more than a selected criterion (based on response variability) were identified. Of all mixture responses, 37% (59/158) involved mixture suppression (mixture response < MEC response), only 4% (6/158) were greater than the MEC, and 59% (94/158) were classified as not different than the response to the MEC. Most neurons that displayed mixture suppression did so at several mixture concentrations. 3. Sucrose suppression (mixture response < sucrose response) was prevalent among neurons most responsive to sucrose and for the mixtures that contained the stronger sucrose concentrations. Among neurons that displayed sucrose suppression, the magnitude of suppression was significantly correlated with sucrose response magnitude but not with QHCl response magnitude. These and other factors suggest that a neuron's capacity to display sucrose suppression to sucrose+QHCl mixtures is related to its sucrose sensitivity. 4. QHCl suppression (mixture response < QHCl response) was less prevalent than sucrose suppression, and the neurons that displayed QHCl suppression were almost exclusively a subset of those that displayed sucrose suppression to the same or different mixtures. This finding and the observation that one-third of all mixture responses involved mutual suppression (response to the mixture less than that to either component alone), suggest an association between the factors underlying sucrose suppression and QHCl suppression. 5. The across-neuron patterns (ANPs) of taste responses, which are thought to represent taste quality, were compared for mixtures and components. In general, the ANP for each mixture was similar to (significantly correlated with) the ANP of the more stimulatory component. However, for the mixture that evoked the greatest sucrose suppression, the mixture ANP was more similar to the ANP of the less stimulatory component.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Enduring alterations in neurophysiological taste responses after early dietary sodium deprivation.

1. Neurophysiological taste responses from neurons in the nucleus of the solitary tract (NST) were studied in four groups of rats during chemical stimulation of the tongue with sodium and non-sodium salts, citric acid, and sucrose. The four groups of rats consisted of those fed a NaCl-deficient diet (0.03% NaCl) from day 3 postconception to at least day 50 postnatal (deprived rats), rats initially fed the NaCl-deficient diet during development and then placed on a NaCl-replete diet at adulthood for > or = 5 wk (control-deprived rats), and rats always fed the NaCl-replete diet (control rats). 2. Compared with controls, dietary NaCl deprivation instituted early in development resulted in highly attenuated average response frequencies to sodium salts (as much as 50%) but not to nonsodium salts and nonsalt stimuli. Concomitantly, most NST neurons in deprived rats responded "best" to NH4Cl and few responded best to NaCl. This is in contrast to that observed in controls, where the same proportion of neurons responded best to NaCl and best to NH4Cl. 3. Taste responses in recovered rats exhibited a hyperresponsiveness to many sodium salts compared with controls. That is, sodium salts elicited average response frequencies significantly greater (as much as 100%) than that obtained in controls. The proportions of neurons responding best to NaCl or to NH4Cl were opposite to that in deprived rats. In recovered rats, the proportion of neurons that responded best to NaCl was much greater than that which responded best to NH4Cl. 4. Rats deprived of dietary NaCl only as adults responded like controls. Therefore the environmental manipulations must occur during early periods of development. 5. These findings show that early dietary manipulations of sodium and subsequent replacement of dietary sodium have neurophysiological effects relatively selective for sodium-elicited taste responses. Furthermore, because recordings in recovered rats were obtained > or = 5 wk after feeding the NaCl-replete diet, it appears as though early NaCl deprivation permanently alters the functional organization of the NTS. Although it is likely that alterations in peripheral neural activity play a role in the functional development of NTS neurons responsive to taste stimuli, other non-activity-related factors may also be important.

Age Factors↗

Voltage dependence of the rat chorda tympani response to Na+ salts: implications for the functional organization of taste receptor cells.

1. Voltage-clamp and current-clamp data were obtained from a circumscribed region of the anterior rat lingual epithelium while simultaneously monitoring the afferent, stimulus-evoked, neural response from the same receptive field. 2. Chorda tympani (CT) responses at constant Na(+)-salt concentration were enhanced by submucosa negative voltage clamp and suppressed by positive voltage clamp. The complete CT response profile, including the time course of adaptation, was not uniquely determined by NaCl concentration alone. The response could be reproduced at different NaCl concentrations by applying a compensating voltage. 3. The form of the concentration and voltage dependence of the CT response indicates that the complete stimulus energy is the Na+ electrochemical potential difference across receptor cell apical membranes, and not Na+ concentration alone. This is the underlying principal behind the equivalence of chemical and electric taste for Na+ salts. 4. CT responses to sodium gluconate (25 and 200 mM) and 25 mM NaCl produced amiloride-insensitive components (AIC) of low magnitude. NaCl at 200 mM produced a significantly larger AIC. The AIC was voltage-clamp independent. The relative magnitude of the AIC was positively correlated with the transepithelial conductance of each salt. This suggests that the large AIC for 200 mM NaCl results from its relatively high permeability through the paracellular pathway. 5. Analysis of the CT response under voltage clamp revealed two anion effects on Na(+)-salt taste, both of which act through the paracellular shunt. 1) Anions modify the transepithelial potential (TP) across tight junctions and thereby modulate the cell receptor potential. This anion effect can be eliminated by voltage clamping the TP. 2) Sufficiently mobile anions facilitate electroneutral diffusion of Na+ salts through tight junctions. This effect is observed especially when Cl- is the anion and when the stimulus concentration favors NaCl influx, allowing Na+ to stimulate receptor cells from the submucosal side. Because the submucosal intercellular spaces are nearly isopotential regions, this effect is insensitive to voltage clamp of the TP. The large AIC associated with this anion effect is due to the low permeability of amiloride.

Afferent Pathways↗

Taste responses of neurons in the nucleus of the solitary tract of awake rats: an extended stimulus array.

1. Fifty-seven taste neurons were isolated in the nucleus solitary tract (NST) and tested with 15 sapid chemicals. On average, NST neurons responded well to NaCl, sucrose, monosodium L-glutamate (MSG), NaNO3, and glycine (mean = 8.2-11.0 spikes/s). Mean responses to KCl, NH4Cl, HCl, malic acid, and quinine HCl (QHCl) were low (mean = 0.7-2.9). The average responses to the other stimuli (citric acid, MgCl2, fructose, maltose, and polycose) fell between these extremes (mean = 4.3-5.1). 2. On the basis of the largest response to the four standard stimuli, the neurons were classified as follows: 15 NaCl-best, 23 sucrose-best, 17 citric acid-best, and 2 QHCl-best. 3. The NaCl-best neurons responded robustly and nearly equally to the three sodium salts (mean = 15.7-20.8) but much less so and more variably to the nonsodium, chloride salts (mean = -0.1-4.6). Sucrose-best neurons responded strongly to sucrose, glycine, and MSG (mean = 13.7-17.8), but only moderately to the other sugars (fructose and maltose) and to polycose (mean = 8.4, 9.8, and 8.8, respectively). 4. Citric acid-best neurons responded moderately to citric and malic acid (mean = 9.4 and 4.7), but less so to HCl (mean = 3.1). The two QHCl-best neurons responded moderately to QHCl and MgCl2 (mean = 12.0 and 9.5), but weakly or not at all to the other stimuli (mean = -1.1-3.1). 5. Unlike parabrachial taste neurons, none of the medullary taste cells responded specifically to Cl(-)-containing chemicals. The responses that did occur to nonsodium salts were weak and variable and often occurred in either citric acid-best or QHCl-best neurons, rather than in those that responded vigorously to sodium salts. Similar relationships have been observed in anesthetized preparations. 6. A hierarchical cluster analysis for 57 neurons across 15 stimuli produced four second-order clusters that consisted primarily of NaCl-best, sucrose-best, citric acid-best, and QHCl-best neurons, respectively. Although the analysis for neurons produced only four such clusters, a similar analysis for the 15 stimuli separated the sodium salts (NaCl and NaNO3), nonsodium salts (KCL, NH4Cl, and MGCl2, sweeteners (sucrose, maltose, fructose, and glycine), acids (citric acid and malic acid), and QHCl. 7. Monosodium glutamate activated both NaCl-best and sucrose-best neurons, but the stimulus analysis clumped it with the sodium salts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Statistical analysis of neural organization.

1. The responses of 32 taste neurons in the solitary nucleus of the rat to 12 stimuli were analyzed with multidimensional scaling (MDS) and cluster analysis (CA) procedures. These analyses of empirical taste data were compared with similar analyses of two model data sets of known configuration to help clarify the implications of these methods commonly used in forming conclusions about the organization of the taste system. 2. To relate to possible conclusions about groupings in taste, both model data sets were chosen as the best possible examples of ungrouped data, the first being completely regular (in the form of a checkerboard) across the taste space, the second randomly arranged. The analysis of the present empirical data appear to be similar to the present ungrouped models, more so the random than the regular model, in the sense that all are amenable to grouping. 3. Because of the similarity of these model MDS and CA solutions to the present empirical solutions and to most published analyses of this sort, the idea is suggested that the appearance of the plots per se for empirical data does not support the conclusion of grouping. And, technically, MDS and CA do not have the statistical power to provide conclusions about issues of neural organization. 4. MDS and CA analyses have two very powerful roles relating to their ability to disclose the hidden organization of complex data sets; they may lend support for or refute theories about the data sets developed from other considerations, and may help generate theories for further consideration. The question of groupings is only one of many such issues. 5. Because data in the present and other reports are quite adequately accounted by MDS solutions of low dimensionality, it is suggested that their organization is characterized as continuous (i.e., rather than belonging to several disjoint spaces). 6. The use of correlations as distance measures in MDS and CA procedures distorts the spatial solutions, making analysis by visual inspection misleading. For example, using correlations, the true or natural spatial arrangements of data sets are probably less circular or spherical than shown in published MDS solutions. Also they are probably more evenly distributed across the space in the sense that the points are actually more concentrated toward the centers of the spaces; this may have strong influences on interpretations of the general form of the solutions. CA solutions can be influenced in analogous fashion. These problems of distortion of the solutions can be avoided with use of direct, linear estimates of distances. (ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Responses of single hamster parabrachial neurons to binary taste mixtures of NaCl with sucrose or QHCl.

1. Although human psychophysical responses to taste mixtures have been investigated extensively, there have been few reports on the neurophysiological coding of taste mixtures in the mammalian gustatory system. In recent studies we have investigated the responses of single third-order neurons in the hamster parabrachial nucleus (PbN) to anterior tongue stimulation with binary mixtures of heterogenous taste stimuli including sucrose+QHCl, sucrose+citric acid, and NaCl+citric acid. Some of these stimulus combinations evoked mixture suppression, or response frequencies that were less than that evoked by the more effective component (MEC) presented alone, which is analogous to the mixture suppression reported in human psychophysical studies of similar taste mixtures. In the current report we extend our investigation to include NaCl+QHCl and NaCl+sucrose mixtures. 2. The action potentials of single PbN neurons were recorded extracellularly. Four concentrations of each stimulus were employed: NaCl and sucrose at 0.001, 0.01, 0.1, and 1.0 M; QHCl at 0.00032, 0.0032, 0.032, and 0.1 M. All stimuli were tested alone and in mixture; the NaCl+sucrose and NaCl+QHCl mixtures were formed by pairing the four concentrations of each stimulus with the strongest concentration of the other stimulus. 3. For both NaCl+sucrose and NaCl+QHCl mixtures, the response frequencies evoked by the mixtures did not differ from those evoked by the MEC presented alone, whether averaged across all neurons or across subgroups of NaCl- or sucrose-best cells. Furthermore, the across-neuron patterns (ANPs) of mixture responses were similar to those of the MECs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gustatory neural coding in the monkey cortex: the quality of saltiness.

1. We analyzed the activity of single neurons in the insularopercular cortex of four alert cynomolgus monkeys in response to the oral application of four basic taste stimuli (glucose, NaCl, HCl, and quinine HCl) and fruit juice and to a range of 17 sodium and lithium salts with a variety of anions. 2. Neurons responsive to gustatory stimulation were encountered in an area of 34.5 mm3 (2.0 mm A-P x 2.5 mm M-L x 6.9 mm D-V). Taste cells composed 46 (4.5%) of the 1,028 neurons whose sensitivities were tested. Nongustatory cells included those responsive to mouth movements (20.4%), tactile stimulation in the mouth (3.4%), and visual approach of the stimulus (0.7%). The functions of the remaining 71.0% could not be determined. 3. The mean spontaneous discharge rate of these cortical taste cells was 4.4 spikes/s (range, 0.1-23.8 spikes/s). The mean breadth-of-tuning coefficient was a moderate 0.72 (range, 0.15-1.00). Inhibitory responses were nearly nonexistent. 4. There was no evidence that taste cells with similar functional characteristics were clustered within the cortex, i.e., there was no apparent topographic organization of taste qualities. 5. The 46 taste cells were divisible into three functional types, based on their response profiles to the four basic stimuli used here. The types could be characterized as sweet-, salt-, and quinine-oriented. 6. A taste space was generated from correlations among the response profiles evoked by the stimulus array. The 17 salts formed a coherent group from which the other basic stimuli were separated. Glucose was closest to the salt group, followed by quinine and HCl. 7. Within the salt group, the four halides (NaCl, LiCl, NaBr, LiBr) formed a tight cluster; the 11 stimuli with acetate, citrate, phosphate, sulfate, and tartrate anions joined with monosodium glutamate and Na bicarbonate to form two closely related clusters; Na succinate was somewhat distinct from the others, and Na carbonate was most separate. 8. The relative qualities of the salts did not relate systematically to anionic size, promotion of sodium transport, or molar conductivity. 9. The configuration of stimuli in this taste space was compared with that in a space derived from human descriptions of the relative similarities of many of these same stimuli. Using the position of NaCl as a reference, the distances to all other stimuli common to the two studies was measured.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗