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Biomedical subjects

J R Mason

Publications and source records attributed to J R Mason.

At least 55 records · Page 3Linked to original sources

A dose-escalation study of carboplatin/cyclophosphamide/etoposide along with autologous bone marrow or peripheral blood stem cell rescue.

Twenty patients have received 21 courses of high-dose cyclophosphamide (6 g/m2 over 4 days), etoposide (1,800 mg/m2 over 3 days), and carboplatin (800 to 1,600 mg/m2 by continuous infusion over 96 hours) and autologous bone marrow or peripheral blood stem cell rescue. The maximum tolerated dose of this regimen included these doses of cyclophosphamide and etoposide with a total of 1,600 mg/m2 carboplatin. Acute renal failure was the dose-limiting toxicity and, at the maximum tolerated dose, was observed in two patients of 14 evaluable courses. Nonhematologic toxicity was otherwise modest, and the overall response rate was 70% in patients with a wide variety of solid hematologic neoplasms.

Acute Kidney Injury↗

Glucose control of staphylococcal enterotoxin A synthesis and location is mediated by cyclic AMP.

The regulation of staphylococcal enterotoxin A (SEA) synthesis in a defined medium was studied using continuous culture techniques. SEA production was repressed by glucose and repression could be overcome by addition of exogenous cyclic AMP. As well as this classical catabolite repression control, addition of glucose to de-repressed steady-state cultures resulted in rapid disappearance of toxin from the medium (also mediated by loss of cyclic AMP). When the toxin dissappeared from the medium, it was taken up again by the bacteria without apparent modification.

Culture Media↗

Chemical repellency in birds: relationship between chemical structure and avoidance response.

We examined how molecular structure of 24 anthranilate and benzoic acid derivatives correlated with drinking behavior in European starlings Sturnus vulgaris. The effectiveness of bird repellents was associated with basicity, the presence of an electron-donating group in resonance with an electron-withdrawing carboxylic group on a phenyl ring, and a heterocyclic ring in the same pi cloud plane as the phenyl ring. Of the benzoic acid derivatives tested in this study, methyl, ethyl, dimethyl, and linalyl anthranilate as well as anthranilic acid and 4-ketobenztriazine were repellent to birds. Water consumption was significantly reduced relative to control levels at concentrations as low as 0.05% (weight/volume) for the best repellents. Further statistical tests showed that reduction in consumption for the best repellents was absolute, not significantly different from zero consumption. Anthranilic acid isomers were moderately good repellents. The ability to generate a model predicting repellency allows for the efficient identification and development of ecologically sound, nonlethal, taxa-specific repellents to be used for the protection of wildlife in agricultural and industrial applications.

Animals↗

Cloning and expression of the plasmid-encoded benzene dioxygenase genes from Pseudomonas putida ML2.

Hybridization using heterologous dioxygenase gene probes indicated the presence of the genes encoding the enzyme benzene dioxygenase on a 112 kb plasmid from Pseudomonas putida ML2. They were identified as benzene dioxygenase genes (bed ABC1C2) by cloning in Escherichia coli and analysis of expression by Western blotting using antibodies raised to the four polypeptides of purified benzene dioxygenase.

Cloning, Molecular↗

A comparison of the discriminatory ability and sensitivity of the trigeminal and olfactory systems to chemical stimuli in the tiger salamander.

Trigeminal receptors can respond to a wide variety of chemical stimuli, but it is unknown whether these receptors mediate discrimination between chemical stimuli matched for equal perceptual intensity. The present electrophysiological and behavioral experiments address this issue using tiger salamanders, Ambystoma tigrinum, and four compounds (amyl acetate, cyclohexanone, butanol, and d-limonene). In addition, the relative sensitivities of the trigeminal and olfactory systems to these compounds are compared. In electrophysiological cross-adaptation experiments (amyl acetate vs cyclohexanone; butanol vs d-limonene), there was complete cross adaptation such that only concentrations above the background (cross-adapting) stimulus concentration elicited responses, suggesting that chemical stimuli may stimulate trigeminal receptors nonspecifically. In behavioral experiments (amyl acetate vs cyclohexanone; butanol vs d-limonene), only animals with intact olfactory nerves could discriminate between perceptually equivalent concentrations, that is concentrations that elicited the same level of responding. Both electrophysiologically and behaviorally, the trigeminal system exhibited higher thresholds than the olfactory system. We conclude that trigeminal chemoreceptors, at least in salamanders, are unable to discriminate between these two pairs of compounds when matched for equal perceptual intensity, and that trigeminal chemoreceptors are less sensitive than olfactory receptors.

Action Potentials↗

Carbon disulfide: a semiochemical mediating socially-induced diet choice in rats.

Gas chromatography/mass spectrometry revealed the presence of both carbon disulfide (CS2) and carbonyl sulfide (COS) on rat breath. Behavioral experiments indicated that rats exposed to an unfamiliar diet moistened with CS2, like rats exposed to an unfamiliar diet placed on the fur of an anesthetized rat, subsequently exhibited enhanced preference for the unfamiliar diet. Rats in experimental groups: (a) interacted for 30 min with a wad of cotton batting powdered with one of two unfamiliar foods (either Diet A or Diet B) and moistened with a dilute, aqueous CS2 solution, (b) ate Diets A and B in succession and finally, (c) were injected with LiCl. In a subsequent choice between Diets A and B, these rats exhibited a preference for whichever of the foods had been present on the cotton batting during (a). Rats in control groups were treated identically to those in experimental groups, except that the diet-coated cotton batting to which they were exposed was moistened with distilled water rather then CS2 solution. Rats in control groups were not affected in their later diet choice by the food present on the cotton batting during (a). These data are consistent with the hypothesis that CS2 is a semiochemical that mediates social influence on diet selection in rats.

Animals↗

Benzene dioxygenase in Pseudomonas putida. Subunit composition and immuno-cross-reactivity with other aromatic dioxygenases.

The terminal oxygenase component of benzene dioxygenase from Pseudomonas putida strain ML2 was shown to contain two subunits, of Mr 54,500 and 23,500, by SDS/polyacrylamide-gel electrophoresis. The native Mr of the terminal oxygenase was estimated to be 168,000 +/- 4000. Polyclonal antibodies raised against each of the subunits cross-reacted with two polypeptides in cell-free extracts from toluene-grown Pseudomonas putida strain N.C.I.B. 11767. The Mr values of these polypeptides were similar to those reported for the subunits from the terminal dioxygenase component of toluene dioxygenase. These polypeptides were present only when this strain was grown on toluene. No cross-reactivity was observed with subunits of the naphthalene dioxygenase or benzoate dioxygenase systems.

Cross Reactions↗

Caffeine enhancement of saccharin but not cyclamate flavor avoidance.

The present experiments were designed to assess whether caffeine, a substance that potentiates human perception of some artificial sweeteners, might also enhance perception of such substances by rats. In Experiment 1, rats were given varied concentrations of saccharin, cyclamate, and caffeine in 2-choice tests. 'Indifference thresholds' for these substances were 3.9 X 10(-4) M, 1 X 10(-3) M, and 1.6 X 10(-7) M, respectively. In Experiment 2, concentrations of saccharin and cyclamate just above and below indifference were used as stimuli in a flavor avoidance learning (FAL) paradigm. 'Suprathreshold' concentrations of saccharin and cyclamate produced reliable FAL while 'subthreshold' concentrations did not. In Experiment 3, rats were exposed to a low concentration of caffeine followed by presentations of subthreshold concentrations of saccharin or cyclamate as stimuli in a FAL paradigm. Saccharin FAL was observed but cyclamate FAL was not, suggesting that caffeine preexposure selectively potentiated detection of saccharin. In Experiment 4, animals were given saccharin or cyclamate with or without prior exposure to caffeine in a FAL paradigm. During subsequent tests, animals were presented with saccharin or cyclamate following exposure to caffeine saccharin or cyclamate mixed with caffeine saccharin or cyclamate alone. Saccharin FAL was observed following caffeine preexposure, but mixing with caffeine had no effect. These findings of selective potentiation are consistent with previous studies of human sensitivity after caffeine preexposure. Moreover, the present results support the notion that inhibitory A1 adenosine receptors are involved in modulating the perceived intensity of some flavors.

Animals↗

Capsaicin and its effects on olfaction and trigeminal chemoreception.

Capsaicin injections severely reduced or eliminated nasal trigeminal responses to 3 odorants (Experiment 1). However, capsaicin treated animals exhibited no deficits in locating buried food, in odor avoidance learning, or in operant odor detection and discrimination (Experiments 2 and 3). In addition, capsaicin desensitization did not affect responsiveness to salty or sour, but may have raised rejection thresholds for bitter (Experiment 4). Finally, while desensitized animals rejected menthol solution, they consumed relatively more than controls, suggesting that capsaicin may have menthol sensitivity. The present results suggest that substance P-containing fibers mediate trigeminal responsiveness to odorants and irritants but that the loss of this responsiveness does not appreciably affect smell or taste, per se.

Animals↗

Nasal trigeminal chemoreception: responses to n-aliphatic alcohols.

Odorant molecules can stimulate nasal trigeminal receptors, but the properties of such molecules which make them effective stimuli are largely unknown. In the present study, we obtained integrated multiunit responses from the ethmoid branch of the rat trigeminal nerve to a homologous series of aliphatic alcohols. Our aim was to determine whether lipid solubility might correlate with stimulus efficacy. Response thresholds (ranging from 3000 ppm for methanol to 3 ppm for octanol) decreased with increasing carbon chain length, suggesting that lipid solubility is important for stimulus effectiveness. One plausible explanation for the importance of lipophilicity is that the more lipid soluble a substance, the more easily it can penetrate epithelial layers to reach chemoreceptive trigeminal nerve endings. Since all stimuli at vapor saturation elicited responses within 0.5 s, and because diffusion of stimulus molecules through epithelium is slow, we speculate that trigeminal nerve endings lie closer to the epithelial surface than previously thought.

Alcohols↗

Olfactory responses of aquatic and terrestrial tiger salamanders to airborne and waterborne stimuli.

Electro-olfactograms (EOGs) were used to assess olfactory responding by aquatic larval and terrestrial adult tiger salamanders (Ambystoma tigrinum) to airborne volatile compounds, and volatile and non-volatile compounds in aqueous solution. Both forms of salamander showed saturation effects to presentations of airborne stimuli (Fig. 2). Saturation was not observed, however, to stimulus presentations in aqueous solution (Figs. 2, 3). When threshold values and concentration-response curve parameters were compared, non-volatile amino acids in solution were more potent stimuli for larvae while airborne volatiles were more potent stimuli for adults (Tables 1, 2). We infer that metamorphosis in the tiger salamander is accompanied by changes in olfactory response characteristics, due possibly to changes in receptor population, changes in perireceptor properties (e.g. mucus) or to changes in stimulus access.

Ambystoma↗

Effects of learned flavor avoidance on grooming behavior in rats.

In Experiment 1, rats were conditioned to avoid saccharin in tapwater by pairing it with LiCl in carboxymethylcellulose (CMC) applied to the fur. Conditioned flavor avoidance (CFA) of saccharin was then assessed in drinking and grooming tests. In Experiment 2, rats were given saccharin CMC on their fur and NaCl in water (or vice-versa) as conditioned stimuli in a CFA paradigm. Two-choice tests (saccharin vs. NaCl) followed in drinking and grooming contexts. In Experiment 3, rats were given saccharin CMC on one flank and vehicle (CMC only) on the other. After grooming, animals were injected with LiCl and then given 2-choice tests, first between saccharin and water, then between saccharin-CMC and plain-CMC, and finally, between saccharin and water. Strong CFA was exhibited in drinking tests in all 3 experiments. This was not the case in grooming tests. Rats continued to groom when tastant was applied to only one flank (Experiment 1), and exhibited only weak CFA when a different tastant was applied to each flank (Experiments 2 and 3). We conclude that grooming can be directed to minimize the ingestion of noxious substances, but that such ingestion is not sufficiently reduced to affect the efficacy of grooming as a delivery method for unpalatable substances (e.g., rodenticides, chemosterilants). We speculate that grooming represents a weakness in rodents' defenses against dietary poisoning, and that it might be used to deliver toxicants as part of crop protection schemes that make use of CFA.

Animals↗

Rat trigeminal, olfactory and taste responses after capsaicin desensitization.

Experiment 1 showed that capsaicin injections severely reduced or eliminated nasal trigeminal responses to 3 odorants. Experiments 2 and 3 investigated whether desensitized animals could behaviorally detect and discriminate odors. Capsaicin treated animals had no measurable deficits in locating buried food, in odor aversion learning, or in operant odor detection and discrimination. Experiment 4 examined whether behavioral responsiveness to salty, sour and bitter tastes was affected by desensitization. Capsaicin injections did not affect responsiveness to salty or sour, but may have raised rejection thresholds for bitter. Broadly, the present results suggest that substance P-containing fibers mediate trigeminal responsiveness to odorants and irritants but that the loss of this responsiveness does not appreciably affect smell or taste, per se.

Animals↗

Profiling, mimicking and masking the flavor of a selected rodenticide.

In Experiment 1, rats drank strychnine solution followed by an injection of LiCl. Generalization of learned strychnine avoidance to 4 non-toxic flavors was then assessed. Additional conditioning and generalization trials followed until 24 flavors had been presented. In Experiment 2, rats were conditioned to avoid individual flavors, or flavor mixtures concocted on the basis of avoidance generalization observed in Experiment 1. Tests followed for generalization of learned avoidance from the simple flavors to the mixtures, from the mixtures to the simple flavors, and from either to strychnine. In Experiment 3, two concentrations of NaCl were mixed with strychnine or one of the flavors (SOA) used in the previous experiments. These stimuli, as well as SOA alone, strychnine alone, and each of the NaCl concentrations, were presented to rats during conditioning. Generalization followed, as in the previous experiments. In Experiment 1, strychnine avoidance generalized to 'bitter' flavors (ps less than 0.01). In Experiment 2, avoidance of flavor mixtures generalized more strongly to strychnine than did learned avoidance of simple flavors (ps less than 0.01). In Experiment 3, NaCl masked or otherwise suppressed the 'bitter' flavor of strychnine or SOA insofar as no groups conditioned with a 'bitter'-salt mixture generalized avoidance to 'bitter' alone (ps less than 0.01). Rats are therefore capable of recognizing the flavor components of strychnine. Moreover, when these components are mixed in proportion to the degree of generalized avoidance, a mimic (either in terms of flavor characteristics or perceived intensity) of strychnine is obtained. Avoidance learning appears useful in the development of rodenticide baits and pre-bait formulations.

Animals↗

Flavor avoidance expressed in grooming by pine voles (Microtus pinetorum): importance of context and hormonal factors.

Pine voles (Microtus pinetorum) were given sipper tubes containing saccharin solution, and after drinking, were injected with 0.15 M LiCl. Subsequently, two-sipper tests were given to assure the presence of conditioned flavor avoidance (CFA), and then animals were presented with saccharin in carboxymethyl-cellulose on their own fur (autogrooming), or on the fur of cagemates (allogrooming). CFA was expressed in two-sipper tests, and during allogrooming of material from a cagemate's fur, but not during autogrooming. Failure to express CFA during autogrooming was associated with high circulating levels of corticosterone and cortisol, steroids implicated in behavioral arousal. These results are consistent with previous work showing that rats and mice will ingest flavors while grooming that they would otherwise avoid. We speculate that our findings provide a plausible explanation for the successful use of grooming to increase the ingestion of unpalatable toxicants.

Adrenal Cortex Hormones↗