Biomedical subjects

H J Grill

Publications and source records attributed to H J Grill.

At least 37 records · Page 2Linked to original sources

PubMed1998

Differential characteristics of two new tumorigenic cell lines of human breast carcinoma origin.

Permanent human tumor cell lines are an important tool for the study of breast cancer. Two new breast cancer cell lines (BrCa-MZ-01 and BrCa-MZ-02) were isolated from a solid tumor and a pleural effusion, respectively. One cell line was established from a medullary carcinoma, the other from a ductal carcinoma. These cells exhibit ultrastructural and immunohistochemical features of epithelial cells of mammary origin. Intermediate filament and cytokeratin typing showed a clear predominance of the simple-epithelial cytokeratins CK 8, CK 18 and CK 19, although the expression was reduced in comparison to the hormone receptor-positive reference cell lines MCF-7 and ZR-75-1. Both cell lines produced slow-growing tumors after subcutaneous (s.c.) transplantation of 1 x 10(7) viable tumor cells into nude mice. The cell line BrCa-MZ-01 expresses the estrogen and progesterone receptor, whereas the cell line BrCa-MZ-02 remains negative. Both cell lines are positive for secretion of platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), whereas interleukin-6 (IL-6) is only secreted by the cell line BrCa-MZ-02.

Aged↗

PubMed1998

Serotonin receptors in the caudal brainstem are necessary and sufficient for the anorectic effect of peripherally administered mCPP.

The role of caudal brainstem 5-HT receptors in mediating the anorectic effect of the direct 5-HT2C/1B agonist, mCPP [1-(3-chlorophenyl)piperazine dihydrochloride], was evaluated. We demonstrated, first, that systemic injections of mCPP yielded a dose-related suppression of intra-oral intake of 12.5% glucose in intact rats and in chronically maintained supracollicular decerebrate rats. The results of the decerebrate experiment suggest that 5-HT receptors in the caudal brainstem are sufficient for mediating the drug's intake effect. We also showed a dose-related intake suppression when mCPP was delivered to the fourth ventricle of intact rats, with potent suppression obtained at doses well below threshold for systemic administration. Whether and to what extent the 5-HT2C/2A antagonist, mesulergine reverses the intake suppression that follows systemic or 4th i.c.v. injection of mCPP was examined. Fourth i.c.v. co-administration of mesulergine (60 microg) and mCPP (40 microg) eliminated the approximately 50% intake suppression observed when mCPP was delivered alone, a result that affirms the receptor selectivity of the 4th i.c.v. agonist effect. We showed, further, that 4th i.c.v.mesulergine (60 microg) completely reversed the intake suppression produced by systemic mCPP (2 mg/kg). The latter result indicates that stimulation of 5-HT receptors in the caudal brainstem is necessary for the intake suppression produced by systemic administration of this 5-HT agonist in the intact rat.

Animals↗

PubMed1997

Contribution of caudal brainstem to d-fenfluramine anorexia.

Of the central 5-HT substrates that may mediate the anorexic actions of systemically administered d-fenfluramine (d-FEN), those in the forebrain have received the most attention. As a counterpoint to this forebrain focus, we evaluated the contribution of caudal brainstem substrates to the anorexic action of d-FEN. Two experimental protocols were employed. In one we compared the feeding response (intra-oral intake of 12.5% glucose) of intact and chronic supracollicular decerebrate (CD) rats to systemic administration of d-FEN. In the other, d-FEN was administered via fourth intracerebroventricular (ICV) injection to determine whether a dose-related suppression of intra-oral intake could be obtained. A dose-dependent suppression of intra-oral intake was obtained in the CD rat treated with d-FEN (0-8 mg/kg, delivered IP 20 min before testing). The threshold dose was two to three times higher in CD rats than in their intact controls, but the dynamic range of the dose-response curves of the two groups were overlapping with similar slopes of decline and with comparable maximal intake suppression. Fourth ICV administration of d-FEN in the intact rat yielded a dose-related suppression of intra-oral intake. Intake was also suppressed by fourth ICV d-FEN (30 mg) when rats drank 12.5% glucose solution from a spout. The reduced intra-oral intake following fourth ICV d-FEN treatment was partially attenuated by the systemic administration of the serotonin antagonist metergoline (0.4 mg/kg; IP). The CD results demonstrate the sufficiency of caudal brainstem receptors in mediating intake suppressive responses to systemic d-FEN. The fourth ICV results suggest further that 5-HT receptors in the caudal brainstem play a significant role in normal meal size control in the neurologically intact rat.

Animals↗

PubMed1997

Intake suppression after hepatic portal glucose infusion: all-or-none effect and its temporal threshold.

The effects of hepatic portal infusions of isotonic glucose on glucose intake (3.2%) were evaluated with use of the intraoral intake test, which, unlike traditional tests, permits delivery of portal infusions in explicit temporal relationship to intake onset in nondeprived rats. Continuous or discontinuous portal infusions (0.1 ml/min) of isotonic glucose or saline were initiated 0, 30, 60, or 120 min before meal onset. Jugular infusions of isotonic saline or glucose and portal infusions of isotonic saline were without effect. For all effective portal glucose infusions, intake was suppressed by approximately 30% of baseline values. Because the duration (and quantity) of effective portal glucose infusions varied by a factor of 10, we conclude that intraoral intake suppression under these conditions is all or none in nature. Whether an intake suppression was obtained depended more on when the infusion was delivered than on how much was infused. Thus 1.5 ml of isotonic glucose infused between 60 and 45 min before the intake test was effective, whereas 3.0 ml infused for the 30 min before intake was without effect. These results suggest that the liver participates in the control of future intake but not in the termination of an ongoing meal. The temporal requirement for intake suppression should be considered in analyses of the metabolic, hormonal, and/or neural mechanisms that underlie the liver's contribution to intake control.

Animals↗

PubMed1997

Reward comparison in chronic decerebrate rats.

The simultaneous contrast paradigm was used to evaluate responsiveness to a low (0.05 M) and a high (0.5 M) concentration of sucrose under two conditions in intact and chronic decerebrate rats. In one condition the low concentration was presented on one day and the high concentration on another. In the other condition presentation of the two concentration was alternated within the same daily session. In each case there was a total of 40 trials/day during which the stimulus was delivered intraorally for 2 s at a rate of 1.5 ml/min with a 30-s intertrial interval. The results showed that the intact rats always licked more for the high than for the low concentration of sucrose but that the magnitude of the effect was larger when given the opportunity to compare the two concentrations within the same daily session. The decerebrate rats produced a similar pattern, but the concentration effect was evident only when the stimuli were alternated within the same daily session. These data stand as the first evidence that the isolated caudal brain stem is adequate for the expression of a behavior that depends on comparison processes involving short-term memory.

Animals↗

PubMed1997

Effect of oral versus gastric delivery on gastric emptying of corn oil emulsions.

Several studies have shown that fluids delivered to the stomach tend to empty more rapidly than when ingested by mouth. To better characterize the "delivery route effect" for corn oil, rats received intragastric or intraoral infusions matched for concentration and for the rate and duration of stimulus delivery. We showed, first, that more than twice as much oil emptied by the end of 12-min intragastric versus intraoral infusions but that the emptying curves remained roughly parallel for 1 h after infusion offset. Remaining experiments therefore focused on stimulus parameters of relevance to emptying control during stomach fill. Emptying during intragastric infusions approximately doubled with doublings of oil concentration (25-50%), infusion duration (6-12 and 12-24 min), and infusion rate (0.5-1.0 ml/min). Emptying during intraoral infusions, by contrast, was entirely unaffected by these manipulations. Unlike oil emptying, glucose emptying did not vary as a function of delivery route. The nutrient specificity of the delivery route effect cannot be explained in terms of energy density, as the effect was obtained for oil but not for glucose when their energy densities were equated (50% glucose, 25% corn oil). In discussion, we suggest that the oral influence on corn oil emptying during stomach fill is a gating factor that enables the expression of inhibition derived from postgastric nutrient stimulation.

Administration, Oral↗

PubMed1997

Gastric branch vagotomy and gastric emptying during and after intragastric infusion of glucose.

The effect of gastric branch vagotomy (GVX) on the gastric emptying of glucose was evaluated during two phases of emptying control: as the stomach fills and in the postload period. GVX and control rats received a series of intragastric glucose infusions (1.0 ml/min) through indwelling gastric fistulas. In experiment 1, gastric samples were withdrawn either immediately after the offset of 9- or 18-min infusions of 12.5% glucose or at various times up to 36 min postinfusion. In experiment 2, samples were withdrawn either immediately or 30 min after termination of 12-min infusions of 12.5 or 25% glucose. After gastric fill, glucose solute emptying rate was stable over time not influenced by concentration doubling, and, surprisingly, not affected by GVX. During gastric fill, solute emptying rate doubled with concentration in both GVX and control rats. For each concentration, however, glucose emptied during fill at almost twice the rate in GVX compared with control rats. This accelerated emptying of glucose during fill in GVX rats is consistent with a gastric vagal contribution to inhibitory mechanisms (e.g., receptive relaxation) that operate as the stomach fills under normal conditions. The absence of a GVX effect on emptying after fill suggests either that gastric branch vagal efferents play little role in feedback inhibitory control of glucose emptying under normal conditions or that other systems compensate for the function previously served by vagal gastric branch efferents. Further work is required to address the possible role of the gastric vagus in feedback control of gastric emptying when nutritive fluids other than glucose are delivered.

Animals↗

PubMed1996

A new taste reactivity analysis of the integration of taste and physiological state information.

We used conjoint manipulation of taste and physiological state to address the theoretical issue of signal integration. The interaction between taste (glucose concentration) and state (food deprivation) was evaluated using the taste reactivity method in which oral motor responses elicited by direct intraoral infusion are measured. The time frame of the typical taste reactivity paradigm, where observation is limited to the infusion period, was expanded to include the postinfusion interval. In each test session, rats received a series of trials consisting of 15-s intraoral infusions and 45-s postinfusion observation intervals. Two experiments were run in which glucose concentration was varied and rats were run nondeprived and after 24 h food deprivation. In experiment 1, glucose concentrations (0, 3.2, 6.25, 12.5, and 25%) were randomly presented during each test session. In experiment 2, individual glucose concentrations (0, 6.25, or 25%) were presented during separate sessions. For both, a deprivation condition was flanked by nondeprived (baseline) sessions. Concentration-response functions were comparable in both experiments. In each experiment, the shape of the concentration-response function was dramatically different during and after infusions. During infusions, there were no increases in glucose-elicited rhythmic oral responses beyond a very dilute concentration. After infusions, the concentration-response functions appeared linear across the concentration range. In both experiments, deprivation elevated responding only in the after-infusion periods. In experiment 1, the concentration-response function was uniformly elevated (on average, 27%) by deprivation, which if taken at face value would suggest an additive combination of taste and state feedback signals. In experiment 2, however, deprivation increased responding (approximately 30%) for 6.25%, but not for 0 or 25%, suggesting a stimulus specificity of the taste-state integration. Clearly then, the taste-state profiles differed as a function of experimental design. In the GENERAL DISCUSSION, we suggest that the uniform elevation of responding to all glucose concentrations, and to water, seen in experiment 1, may be an artifact of the random presentation of all stimuli during individual sessions. Experiment 2, in which stimuli were presented in a between-sessions design, may provide a truer reflection of the underlying integrative process.

Animals↗

PubMed1995

Effect of occluding the pylorus on intraoral intake: a test of the gastric hypothesis of meal termination.

Meal size does not change in response to food being restricted to the stomach by occlusion of the pylorus. This result has been used as evidence for a gastric model of meal termination where feedback arising solely from the stomach is taken to underlie satiation. Such data provide support for the gastric model, however, only if the rate of gastric emptying during ingestion in the unoccluded condition is slow, such that comparable amounts of food would be found in the stomach at the end of the meal in both the pylorus-occluded and unoccluded conditions. To evaluate this tissue directly, rats were implanted with pyloric cuffs and gastric cannulas and given an intraoral intake test of a 10.5% glucose solution with either the pylorus occluded or unoccluded. At the end of each intraoral intake test, the content of the stomach was removed via the gastric cannula and it's volume and concentration measured. Occlusion of the pylorus did not change meal size, but both the volume and grams of glucose solute found in the stomach were substantially greater in the pylorus-occluded condition. These results are not consistent with the hypothesis that the stomach is the sole source of inhibitory signals that terminate a meal. Cumulative intake would appear to be accurately tracked regardless of its distribution within the digestive tract.

Animals↗

PubMed1995

Ingestive taste reactivity as licking behavior.

In ingestive taste reactivity analysis, the rhythmic oral motor responses observed during intraoral infusion of fluids normally ingested by rats are categorized and counted. These rhythmic movements can be likened to spout-licking in several respects. Both are emitted in the same frequency range (5-8 Hz), organized in a burst/pause pattern, and serve the function of intraoral transport of fluid into position for swallowing. The parallel suggests that a temporal pattern analysis, based on the spout-licking literature, can be fruitfully applied to the rhythmic movements that attend intraoral infusion. We provide a demonstration of such an analysis using an electromyographic (EMG) recording-based method for automated event detection. Eight rats received a 37.5% glucose solution (1.0 ml/min) in a series of 120 s infusion trials (45 s intertrial intervals) that was extended until the fluid was rejected. Movement counts declined 19.1% from the first to the last complete trial. Parameters derived from the pattern analysis (number of bursts, mean burst duration, pause durations, coefficient of variation for the distribution of within-burst intermovement intervals) were affected to a greater extent. The results indicate the potential value of temporal pattern analysis for various applications of the taste reactivity paradigm.

Animals↗

PubMed1995

Fourth ventricle injection of corticotropin-releasing factor and gastric emptying of glucose during gastric fill.

The effect of corticotropin-releasing factor (CRF) administered into the fourth ventricle on the gastric emptying of a 12-ml intragastric infusion of 12.5% D-glucose was examined in nondeprived male rats. All three CRF doses tested (10, 100, and 1,000 pmol) significantly reduced (by 28, 29, and 44%, respectively) the amount of glucose emptied from the stomach at the end of the 12-min (1.0 ml/min) gastric infusion interval. The 10 pmol effective dose is the lowest yet reported to influence gastric emptying. The receptor specificity of the exogenous CRF (1,000 pmol) effect was demonstrated by its complete blockade by preinjection of alpha-helical CRF-9-41 (10 nmol) into the fourth ventricle. Injection of the antagonist alone, however, did not affect glucose emptying, indicating little activation of the targeted receptors under the present nonstressful, baseline conditions. Our results suggest that of the central CRF receptor systems that influence gastric emptying, those in the caudal brain stem, targeted by fourth ventricular injection, may be of particular importance.

Anastomosis, Surgical↗

PubMed1995

Parabrachial nucleus lesions impair feeding response elicited by 2,5-anhydro-D-mannitol.

Systemic injection of the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits a feeding response and induces c-fos activity in the parabrachial nuclei (PBN). We used bilateral ibotenic acid lesions of PBN to determine whether the activation inferred from c-fos activity was causally related to the feeding response. The relationship between the PBN lesion and feeding behavior was also examined with the glucose analogue 2-deoxy-D-glucose (2-DG). The PBN lesions interfered with the feeding response to 2,5-AM but spared the feeding response to 2-DG. Rats were also tested in a conditioned taste-aversion paradigm. Differences were observed in the relationship between lesion extent and behavioral deficit for feeding responses to 2,5-AM and taste-guided intake after taste-aversion conditioning. These data provide the first demonstration that central lesions can disrupt feeding responses to peripherally acting 2,5-AM. The results suggest that the neural substrate for this response differs from that mediating taste-aversion conditioning and from that involved in the feeding response to 2-DG.

Animals↗

PubMed1995

Sodium specificity of salt appetite in Fischer-344 and Wistar rats is impaired by chorda tympani nerve transection.

Unlike other rat strains, the sodium-replete Fischer-344 (F344) strain shows no innate preference for NaCl and displays more aversive and fewer ingestive oral motor responses to orally infused NaCl when tested in sodium balance. Despite these differences, F344 rats show an increase in preference for NaCl in response to sodium depletion. The present study was designed to determine whether the salt appetite of sodium-depleted F344 rats is cation specific and whether such selectivity is mediated in part by an intact chorda tympani nerve. Sodium-depleted (10 mg furosemide) F344 (n = 13) and Wistar (n = 16) rats were permitted repeated access to nine stimuli (water, and 0.05 and 0.3 M NaCl, KCl, NH4Cl, and CaCl2), presented randomly in 10-s trials. One-half of the rats had their chorda tympani nerve sectioned (CTX). Under conditions of sodium depletion, both strains discriminated NaCl from other chloride salts. CTX significantly impaired the selectivity of the licking behavior in both strains, suggesting that sodium-specific licking is partially mediated by anterior tongue taste receptors. These findings suggest that both sodium-depleted F344 and Wistar rats are comparable in their abilities to recognize NaCl, to distinguish it from other salts, and to respond selectively to it, despite the fact that sodium-replete F344 and Wistar rats differ greatly in their NaCl preference.

Animals↗

PubMed1995

Gustatory detection thresholds after parabrachial nuclei lesions in rats.

Rats with either electrolytic (Experiment 1) or excitotoxic lesions (Experiment 2) that had been electrophysiologically centered in the gustatory zone of the parabrachial nuclei (PBN) were tested for sucrose and NaCl taste detection thresholds in a conditioned avoidance task. With 1 exception, all of these rats had previously shown severe deficits in acquiring an LiCl-based conditioned taste aversion (CTA) to sucrose, NaCl, or alanine. The rats with excitotoxic lesions also had failed to express a depletion-induced sodium appetite. Despite the uniformity of these deficits, the rats with lesions exhibited varied performance in the detectability task. Roughly 1/3 of the rats did not perform competently, 1/3 had elevated thresholds, and 1/3 showed no or only marginal impairments in taste detectability. These findings demonstrate that the elimination of CTA following PBN lesions is not necessarily linked to an impairment in taste signal detection. Thus, PBN-induced deficits on 1 taste-related task do not entirely correspond with impairments on another.

Animals↗

PubMed1994

Ingestion, gastric fill, and gastric emptying before and after withdrawal of gastric contents.

The notion that satiation signals are derived from the stomach with no additional contribution of postgastric sources (J. A. Deutsch. In: Handbook of Behavioral Neuroscience, Food and Water Intake. 1990, vol. 10, p. 151-182) was evaluated in two experiments. In experiment 1, the gastric contents were withdrawn after the rat met the satiety criterion for an initial intraoral intake test (12.5% glucose delivered at 1.0 ml/min). Ten minutes later, the intraoral infusion was continued until the rat again met the satiety criterion. We found that rats reingested an amount closely corresponding to the amount withdrawn, in agreement with previous studies using spout-licking tests. Despite a lower gastric emptying rate during reingestion than during the initial test, the amount recovered from the stomach (both volume and solute content) after reingestion was significantly less (gastric volume 16% less; gastric glucose 18% less) than that withdrawn initially. In experiment 2, a portion (8 ml) of the gastric contents was removed after the end of an initial intraoral intake test and, after 10 min, rats were again given an opportunity to ingest to satiety. The procedure was repeated for a total of three withdrawals (24 ml) and three reingestion opportunities. Rats accurately replaced the amounts withdrawn such that net intake at the end of the experiment did not differ from that ingested during the initial test. In addition, the amount recovered from the stomach after the terminal test was considerably less (gastric volume 25% less; gastric glucose 29% less) than that recovered at the end of single-test control sessions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Neurological dissociation of gastrointestinal and metabolic contributions to meal size control.

A method was developed to separate gastrointestinal (GI) and metabolic contributions to meal size and applied to intact and chronic decerebrate (CD) rats. The effect of a 10-ml milk diet preload or 24 hr of food deprivation on the consumption of a 0.1-M sucrose solution was compared with intake in a no-deprivation/no-preload condition. In the no-deprivation/no-preload condition, rats were given their normal complement of feedings but had the contents of their stomachs removed via a gastric cannula before the intake test. Compared with the no-deprivation/no-preload condition, intact and CD rats consumed significantly less after the preload, but only intact rats ate more after deprivation. Thus intact rats were sensitive to both GI and metabolic influences on intake, whereas CD rats responded to only the GI manipulation. The experiments showed that GI and metabolic contributions to the deprivation response are mediated by neural structures that are at least partly nonoverlapping. The GI component is likely to be contained within the caudal brainstem. The neural systems required for the response to the metabolic changes accompanying deprivation appear to be more widely distributed.

Animals↗

PubMed1994

A behavioral probe of the growth of intake potential during the inter-meal interval in the rat.

The rat's willingness to ingest glucose after an initial intraoral intake test was probed by beginning a 2nd intraoral intake test at variable durations (1-120 min). In Experiment 1, after an initial meal of 12.5% glucose solution averaging 26.9 +/- 1.7 ml (SEM, n = 10), the size of the 2nd (probe) meal of the same stimulus increased linearly from 4.0 +/- 0.9 ml after a 1-min delay to 15.4 +/- 2.7 ml after a 120-min delay. In Experiment 2, intraoral intake of a more concentrated (37.5%) glucose solution rose more slowly as a function of delay from 2.4 +/- 2.7 ml (SEM, n = 12) to 4.9 +/- 0.6 ml. For each glucose concentration, the linear recovery function and a slope that depends on stimulus concentration are consistent with a role for gastric emptying during the delay in intake recovery. In Experiment 3, rats ingested 12.5% or 37.5% glucose to satiety in an initial test and received, after a variable delay, either the same or the other concentration as the probe stimulus. The same volumes were ingested at each delay whether the glucose concentration of the probe stimulus was the same or was switched from that presented in the initial test. This result shows that the taste and caloric properties of the probe stimulus played no role in determining how much of it would be ingested. Rather, the satiety criterion for the probe test was reached on the basis of the volume ingested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Lesions of the central nucleus of the amygdala. I: Effects on taste reactivity, taste aversion learning and sodium appetite.

Bilateral damage to the central nucleus of the amygdala (CeAX) in the rat blunts need-induced NaCl intake and abolishes daily need-free NaCl intake when measured with a two-bottle test. Such a deficit could be the result of impaired taste function. To assess the taste function of the CeAX rat various taste stimuli were introduced directly into the oral cavity and taste-elicited oral motor responses were measured. Oral motor responses elicited by 0.62 M and 0.13 M sodium chloride, 0.3 M sucrose and 0.01 M citric acid, were similar in control and CeAX rats. Additionally CeAX and control rats acquired a taste aversion for fructose or maltose when either was paired with LiCl. Finally, in CeAX rats, like in control rats, the pattern of oral motor responses to 0.5 M NaCl was dependent on internal state; sodium depletion dramatically altered taste-elicited oral motor behavior. These results suggest that, in the rat, the deficits in NaCl intake behavior that follow CeAX do not appear to be a result of dramatic changes in gustatory function.

Amygdala↗