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Biomedical subjects

J Gibbs

Publications and source records attributed to J Gibbs.

At least 19 recordsLinked to original sources
PubMed1992

Enkephalin is a competitive antagonist of cholecystokinin in the gastrointestinal tract, as predicted from prior conformational analysis.

Prior calculations based on ECEPP (Empirical Conformational Energies for Peptides Program) of the low energy minima for cholecystokinin (CCK) and Met-enkephalin have demonstrated that significant structural features of these two peptides are identical. This result suggested the possibility that Met-enkephalin, as well as other enkephalin analogues of similar structure, could associate with receptors for CCK. To test this theoretical result, we examined the ability of Met-enkephalin and its analogues to bind to peripheral CCK receptors in the rat gastrointestinal tract; in particular, we measured the ability of the opiate peptide to inhibit the effects of CCK in a physiological assay system which we have previously characterized: CCK-induced contraction of the isolated rat pyloric sphincter. We find that Met-enkephalin is an antagonist of the CCK-8-induced contraction, with a IC50 of 110 nM. Furthermore, antibodies against CCK were found to cross-react with Met-enkephalin and its analogues in a manner which suggests a distinct structure-activity relationship. These experimental results strongly support the theoretical results of conformational analysis showing structural similarity between enkephalin and CCK. They further suggest that enkephalins could modulate the response of CCK systems under physiological conditions.

Amino Acid Sequence↗
PubMed1992

The 5-HT1A agonist 8-OH-DPAT attenuates the satiating action of cholecystokinin.

To investigate the dependence of the satiating action of cholecystokinin (CCK) on serotonergic action at central 5-HT receptors, we examined the effect of systemic pretreatment with 8-OH-DPAT (a 5-HT1A agonist that decreases central 5-HT synthesis and release via an action at somatodendritic autoreceptors in the brainstem raphe) on the suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CKK-8). 8-OH-DPAT significantly attenuated the satiating action of CKK-8. This result is consistent with the hypothesis that peripherally acting CCK recruits central serotonergic processes to elicit normal satiety.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Devazepide antagonizes the inhibitory effect of cholecystokinin on intake in sham-feeding rats.

3S(-)-N-(2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl) -1H-indole-2-carboxamide (devazepide), a potent and selective cholecystokininA (CCKA) antagonist, has been shown to reverse the inhibitory effect of exogenously administered CCK-8 on food intake. In all tests, however, the inhibition of food intake could have been due not only to the CCK-8 administered but also to synergistic interactions between administered CCK-8 and endogenous satiety signals, such as glucagon or CCK released from the small intestine, elicited by the postingestive effects of the test diet. To eliminate these possible interactions, we investigated the effect of devazepide on the inhibitory effect of CCK-8 on the intake of a milk diet during 30 min of sham feeding, a procedure that minimizes or eliminates the postingestive satiating effect of food. Under these conditions, devazepide was a potent antagonist of the inhibitory effect of CCK-8 (16 mumol/kg, IP): The approximate ED50 was 625 ng/kg (1.3 nmol/kg) and the threshold dose was between 62.5 and 625 ng/kg.

Animals↗
PubMed1992

False diagnosis of epilepsy in children.

Epilepsy is frequently diagnosed incorrectly through a failure to obtain an adequate history and placing inappropriate emphasis on the electroencephalogram (EEG). We describe four children with common, nonepileptic events who were diagnosed initially as having epilepsy.

Adolescent↗
PubMed1992

Are gut peptides a new class of anorectic agents?

In the past 20 years, the mechanisms of the satiating effect of food that terminate a meal have been investigated intensively in rodents and in humans. This research has revealed that three peptides, cholecystokinin, pancreatic glucagon, and bombesin, released by ingested food from the gastrointestinal tract decrease meal size in a specific, dose-related manner without signs of acute toxicity or tolerance. In humans, the three peptides decrease meal size without decreasing the reported pleasure or satisfaction of the meal. Although their chemical structure and specific effect justify calling these peptides a new class of anorectic agents, not enough work has been done to evaluate their efficacy for weight loss in obese humans or their safety when administered for months.

Animals↗
PubMed1992

Congenital Horner syndrome associated with non-cervical neuroblastoma.

Horner syndrome may be caused by a neuroblastoma involving the cervical sympathetic nervous system. A two-year-old girl presented with Horner syndrome and a discrete, distant neuroblastoma, suggesting that these two conditions represent a more widespread dysgenesis of the sympathetic nervous system.

Child, Preschool↗
PubMed1992

Joint impairment and hand function in the elderly.

OBJECTIVE: To test the contribution of joint impairment to observed hand function (grip strength and Williams Test) in the elderly, using a multivariate model. DESIGN: Cross-sectional observational data (baseline data from an ongoing longitudinal study). SUBJECTS: Five hundred forty-one persons over age 60, including continuing care retirement community (n = 222), homebound (n = 72), and ambulatory (n = 247) respondents. Mean age at assessment 76.7, (SD = 9.0). MEASUREMENT: Independent variables included sociodemographics, physician measures of upper joint impairment, an index of comorbidities derived from physical examination or chart abstract, self-assessed arthritis pain, depression, and anxiety. The dependent variables included grip strength and a modified Williams Test [Williams Test (M)]. MAIN RESULTS: The multiple regression explained 59% (Adjusted R2 = .59) of the variance in grip strength, with joint impairment accounting for a change in R2 of .07. Upper joint impairment and grip strength accounted for 3% and 5%, respectively, of the variance in the Williams Test (M) (total amount of explained variance = 45%). CONCLUSIONS: Demographics explain most of the variance in grip strength and performance on the Williams Test (M). Controlling for demographics, musculoskeletal disease represented by joint impairment is associated with diminished grip strength. Reduced grip strength is associated with poorer performance on the Williams Test (M).

Activities of Daily Living↗
PubMed1992

Intravenous infusion of CCKA-receptor antagonist increases food intake in rats.

To test the hypothesis that endogenous cholecystokinin (CCK) released from the small intestine by ingested food produces a satiating effect by acting at CCKA-receptors, we measured the effect of slow continuous intravenous infusions of three doses of MK-329, a potent and selective CCKA-antagonist, on food intake during 2.5-h tests in 13 Sprague-Dawley male rats after 1 h of food deprivation. MK-329 increased food intake significantly and the lowest dose tested (0.5 mg.kg-1.h-1) produced the most consistent effect on cumulative intake. Part of the increased food intake under these conditions was due to a decrease in the satiating effect of food ingested at the first meal on the postprandial intermeal interval. These results are consistent with, but do not prove, the hypothesis that the satiating effect of endogenous CCK released from the small intestine by ingested food is mediated by CCKA-receptors.

Animals↗
PubMed1991

Effect of a fetal surveillance unit on admission of antenatal patients to hospital.

OBJECTIVE: To analyse the effect of a fetal surveillance unit, which undertakes a wide range of maternal and fetal tests on an outpatient or inpatient basis, on the number and length of antenatal hospital admissions. DESIGN: A comparison of the number and length of antenatal admissions six months before and five months after the opening of the unit on 1 July 1990. MAIN OUTCOME MEASURES: Admission rate, antenatal bed occupancy, and interval from admission to discharge or delivery. RESULTS: The antenatal bed occupancy rate fell by 22% from 174/100 deliveries during the six months before the unit was opened to 136/100 deliveries in the five months after it was opened. The difference in distribution of lengths of admission after the unit was opened from before was highly significant (Mann-Whitney test = 5.14, n = 752 and 679; p less than 0.0001), and this was due to shorter intervals from admission to discharge and from admission to delivery. In contrast, the antenatal admission rate did not change significantly (50/100 deliveries v 49/100 deliveries). There was no significant change in the stillbirth rate (6/1294 births v 8/1372 births; difference between rates = 0.0012, 95% confidence interval-0.0043 to 0.0067). CONCLUSION: Obstetricians are more prepared to discharge antenatal patients from hospital and, similarly, admit patients for delivery rather than for assessment if the patients are reliably monitored on an outpatient basis. If this change in practice is sustained substantial financial and social benefits will result as well as improvements in organisation, audit, teaching, and research.

Female↗
PubMed1991

Infra-additivity of combined treatments with selective D1 and D2 receptor antagonists for inhibiting sucrose reinforcement.

Selective antagonists of either the D1 receptor (SCH 23390) or of the D2 receptor (raclopride) produce a dose-related inhibition of sucrose sham feeding in the rat. We investigated the effect of combined treatments with these antagonists on sucrose sham feeding and observed infra-additivity of inhibition across a range of doses. On the basis of this observed occlusive relationship, we conclude that the relevant D1 and D2 receptor mechanisms mediating sweet taste reward do not function independently.

Animals↗
PubMed1991

Increased food intake after type A but not type B cholecystokinin receptor blockade.

To assess the role of cholecystokinin (CCK) receptors in mediating the satiating effect of an oral preload, overnight food-deprived rats (n = 7) were given access to a high-carbohydrate liquid diet for 40 min. At the end of 40 min, food was removed and rats were injected subcutaneously (SC) with devazepide (DVZ; 1 ng/kg-1 mg/kg), an antagonist selective for the CCK-A receptor, or its vehicle, 0.5% carboxymethylcellulose (CMC). Thirty min after injection, rats were given access to the same liquid food for 60 min. DVZ increased food intake significantly. Furthermore, the effectiveness of a very low dose of DVZ (10 ng/kg) is strong evidence that the effect of DVZ was specific for CCK-A receptors. Three of the rats that increased food intake after DVZ were also tested with L-365,260, an antagonist selective for the CCK-B receptor (10 ng/kg-100 micrograms/kg). L365,260 did not increase food intake significantly. These results confirm and extend previous reports that CCK-A receptor blockade increases food intake after an oral preload. They do not, however, demonstrate a role for the CCK-B receptor in mediating the satiating effect of ingested food under the same experimental conditions.

Animals↗
PubMed1991

Failure to detect increases in brain dopamine metabolism in rats sham feeding sucrose and corn oil.

In a recent study we found that when rats sham fed 6% sucrose, 10% sucrose, and 100% corn oil, the rank order of inhibitory potency for D-1 and D-2 receptor antagonists was 6% sucrose greater than 10% sucrose greater than 100% corn oil. In a complementary study, sham-feeding rats preferred 100% corn oil greater than 10% sucrose greater than 6% sucrose as measured by two-bottle preference tests. The preferences are evidence for the rank order of reward value of these solutions. In the present study we tested the hypothesis that the relative antagonist potencies were due to differential release of DA, dependent on the reward value of the sham-fed solution. Dopamine metabolism, estimated by the ratio of dihydroxphenylacetic acid (DOPAC) to DA, was measured in forebrain-DA terminal fields during sham feeding of 100% corn oil, 6% sucrose, and 10% sucrose. The results did not support our hypothesis: no increase in DA metabolism was observed after the sham feeding of any solution.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Type-A CCK receptors mediate the inhibition of food intake and activity by CCK-8 in 9- to 12-day-old rat pups.

To determine the type of cholecystokinin (CCK) receptor that mediates the inhibitory effects of peripherally administered CCK-8 on food intake and activity in 9- to 12-day-old rat pups, we gave injections of a type-A CCK receptor antagonist, MK-329, or of the type-B CCK receptor antagonist, L-365,260, prior to CCK-8 (IP). MK-329 reversed the inhibitory effects of CCK-8, but L-365,260 did not. This demonstrates that the inhibitory effects of CCK-8 (IP) are mediated by type-A, but not type-B, CCK receptors in pups of this age.

Animals↗
PubMed1991

Satiating effect of bombesin is mediated by receptors perfused by celiac artery.

The abdominal site or sites for the satiety action of exogenous, peripherally administered bombesin (BN) were investigated. By use of a chronic arterial catheterization technique, the effects of 1, 2, and 4 micrograms/kg BN on liquid food intake of nondeprived male rats were assessed. Comparisons were made between the effects of these doses infused into the celiac or superior mesenteric arteries or injected intraperitoneally. The satiating potency of exogenous BN was significantly enhanced by direct administration into the celiac artery, which directly perfuses the stomach, pancreas, liver, spleen, and proximal duodenum. By this route, 4 micrograms/kg BN produced greater than 60% suppression of 15-min food intake. By contrast, BN infused into the superior mesenteric artery was no more effective than intraperitoneal injection. Celiac infusion of 1 micrograms/kg BN produced a suppression (30%) of intake that was equivalent to, or exceeded, that obtained after intraperitoneal injection or superior mesenteric infusion of 4 micrograms/kg. These results strongly support an upper abdominal, and possibly gastric, site for the satiety action of peripherally administered BN.

Animals↗