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Biomedical subjects

M Grace

Publications and source records attributed to M Grace.

At least 253 records · Page 14Linked to original sources

Gastrin, gastric emptying, and gastroesophageal reflux after ranitidine.

In a double-blind study comparing ranitidine to placebo in the treatment of symptomatic gastroesophageal reflux disease (GERD), we assessed gastric emptying time, gastroesophageal reflux, and gastrin response to food. Mean half-time for gastric emptying, measured using 99mTc-sulfur colloid, was 109 minutes in GERD and 102 minutes in nine healthy asymptomatic controls. This difference was not significant, but one-third of GERD had emptying times of 2 S.D.s beyond the mean for the normal controls. The patients with GERD refluxed an average of 2.3% (0.1-10%) of the isotope in 120 minutes compared with only 0.2% (0.0-0.5%) in control subjects. Reflux scans and gastric emptying times did not change with healing of esophagitis or with symptomatic improvement from ranitidine and antacids. There was no relationship between the percentage of the test dose refluxed into the esophagus and the rate of gastric emptying. The mean fasting gastrin concentration in GERD, 133 +/- 12 pg/ml, was higher than in healthy controls, 93 +/- 10 pg/ml (p less than 0.01). After stimulation with a standard meal, the integrated gastrin response (IGR) was similar in controls and GERD patients, but IGR was significantly higher after 6 weeks therapy with ranitidine. These results suggest that: 1) gastric emptying time may be prolonged in some patients with GERD, 2) basal but not food-stimulated gastrin concentrations may be abnormal in GERD, 3) reflux scans have limited use in the investigation of GERD, and 4) ranitidine therapy is associated with an increase in food-stimulated gastrin concentrations.

Adult↗

Psychotherapy with survivors of the Beverly Hills Supper Club fire.

Thirty psychotherapies with survivors of a devastating supper club fire were studied. Treatments were judged in terms of level of completeness, traumatic symptomatology, therapist experience, and therapist sensitivity to the particular disaster influenced level of completion. Nodal points, such as engagement, dosage of affect, and management of transference are described, and case illustrations provided.

Adult↗

Diet of women with Crohn's and other gastrointestinal diseases.

Our results do not support the assertion that subjects with Crohn's disease consume significantly more sugar than controls or those with ulcerative colitis. A subgroup of patients may consume a high proportion of total kilocalories as sugar. In spite of recommendations to increase their dietary fiber intake, subjects with irritable bowel syndrome did not receive significantly more fiber from food sources. Clearly more research is needed to characterize the sugar and dietary fiber intakes of patients with gastrointestinal diseases.

Adult↗

The kappa opioid receptor, ingestive behaviors and the obese mouse (ob/ob).

Recent studies have suggested a role for the kappa opiate receptor and its endogenous ligand, dynorphin, in the central regulation of appetite. In this study we found that the ob/ob mouse was mildly resistant to the ability of three kappa agonists, viz, butorphanol, tifluadom, and ketocyclazocine to induce food intake. In addition, we could find no change in ir-dynorphin levels in 7 areas for the central nervous system. These findings do not provide evidence for a role of kappa opioid feeding system in the pathogenesis of obesity in the ob/ob mouse.

Animals↗

Peer review: a simplified approach.

One hundred and thirteen grant applications were initially reviewed with only a brief outline of the applicant and the proposal and were later reviewed in more detail with the reports of outside experts. The detailed discussion and referees' reports had little impact on the original ratings.

Canada↗

The effect of vagotomy on the satiety effects of neuropeptides and naloxone.

As abdominal vagotomy blocks the satiety effect of cholecystokinin-octapeptide, we felt it would be worthwhile to examine whether the satiety effect of any of the other putative satiety neuropeptides was mediated through the vagus. We confirmed that the satiety effect of peripherally administered cholecystokinin (10 micrograms/kg) was mediated through the vagus. In addition, the satiety effect of peripherally administered TRH (8 mg/kg) also was not present in vagotomized animals. Vagotomy had no effect on the satiety effects of peripherally administered bombesin, calcitonin and naloxone. Nor did vagotomy alter the satiety effect produced by central administration of bombesin, TRH, calcitonin nor naloxone.

Animals↗

Flavor enhances the antidipsogenic effect of naloxone.

Naloxone suppressed ingestion of tap water following a 15 hour deprivation at doses of 20, 10 and 5 mg/kg. Addition of saccharine (0.2%), saline (0.8%), sucrose (2%) and HCl (0.1 M) to tap water resulted in an increased sensitivity to naloxone-induced suppression of water intake following the 15 hour deprivation. The volume of quinine solution (0.1%) consumed was not altered by administration of naloxone. We suggest that naloxone suppresses drinking behavior due to alterations in taste perception.

Animals↗

Tail pinch induced consummatory behaviors are associated with analgesia.

Pinching the tail of a rat results in a set of consummatory behaviors including chewing, eating and licking. In the present study, the effect of tail pinch on pain thresholds was evaluated using the hot-plate and writhing tests. Continuous tail pinch resulted in chewing and markedly lengthened the latency to hind-paw licking and jumping (hot-plate test) when compared with control rats and totally eliminated writhing behaviors. Tail pinch (which induced chewing) for one minute prior to the analgesic testing also prolonged the latency of hot plate-induced behaviors and suppressed the number of writhing behaviors. Naloxone reversed the tail pinch induced analgesia as measured by the hot-plate test, but did not reverse tail pinch-induced analgesia as measured by the writhing test.

Analgesia↗

Dynorphin-(1-13), dopamine and feeding in rats.

Intraventricular administration of the dopamine agonist, bromergocryptine, reliably induces feeding over a narrow dose range with a bell-shaped curve. Bromergocryptine (80 micrograms) induced feeding is inhibited by the dopamine antagonist, haloperidol (0.5 mg/kg) and the opiate antagonist, naloxone (10 and 1 mg/kg). The leucine-enkephalin containing opioid peptide, dynorphin-(1-13) induces feeding which is inhibited by haloperidol (0.5 and 0.1 mg/kg) and by naloxone (1 mg/kg). Of the common satiety factors tested only bombesin (10 micrograms/kg subcutaneously) inhibited both dynorphin-(1-13) and bromergocryptine induced feeding. Cholecystokinin-octapeptide (10 and 20 micrograms/kg, subcutaneously), thyrotropin-releasing hormone (10 and 20 micrograms), ICV) and calcitonin (1 unit, ICV) all failed to inhibit dynorphin-(1-13)-induced feeding. Calcitonin and CCK-8 but not TRH inhibited bromergocryptine-induced feeding. These studies have demonstrated the close interaction between dopaminergic an dopiate systems in the regulation of food intake. The concept of dopamine being primarily responsible for the initiation of chewing behavior and the opiates regulating food ingestion is compatible with the observations reported here.

Animals↗

Protein synthesis in rabbit reticulocytes: characteristics of the protein factor RF that reverses inhibition of protein synthesis in heme-deficient reticulocyte lysates.

During heme deficiency in reticulocyte lysates, the heme-regulated translational inhibitor of protein synthesis (HRI) is activated and shuts off protein synthesis. In partial reactions, HRI phosphorylates the Mr 38,000 subunit (alpha subunit) of eukaryotic initiation factor 2 (eIF-2), which forms a ternary complex, Met-tRNAf X eIF-2 X GTP. The eIF-2 alpha (P) thus formed is not recognized by two eIF-2 ancillary factors, Co-eIF-2B (which promotes the dissociation of the ternary complex at high Mg2+) and Co-eIF-2C (which reverses the inhibition of ternary complex formation), and thus, is presumably inactive in peptide chain initiation. A protein factor, designated RF, which reverses inhibition of protein synthesis in heme-deficient reticulocyte lysates, has been purified from reticulocyte cell supernatant. RF is a high molecular weight (Mr approximately equal to 450,000) protein complex composed of multiple polypeptides. An active RF preparation contains Co-eIF-2B and Co-eIF-2C activities, and these two activities in RF preparation are not inhibited by HRI and ATP--i.e., eIF-2 alpha (P) is recognized. During purification, RF remains associated with eIF-2 activity (eIF-2 X RF) and can be freed of this eIF-2 activity by CM-Sephadex chromatography. Both eIF-2 X RF and RF contain a Mr 38,000 polypeptide component that is indistinguishable from the Mr 38,000 subunit of eIF-2 by two-dimensional gel electrophoresis. It has been observed that a significant part of this Mr 38,000 polypeptide component in eIF-2 X RF and almost the entire Mr 38,000 polypeptide component in RF remain unphosphorylated after prolonged incubation with HRI and ATP. A possible role of this free Mr 38,000 polypeptide in RF action is discussed.

Animals↗

Peptidergic regulation of stress-induced eating.

By use of the model of stress-induced (mild tail pinch) eating we have examined the interrelationships of peptides and monoamines responsible for regulating this behavior. We have shown that the synthetic opiate analog, D-Ala2-Met-enkephalinamide (1 microgram), when administered intracerebroventricularly (icv) reverses the suppressive effects of the serotonin agonist, quipazine (40 micrograms icv), the beta-agonist, isoproterenol (40 micrograms icv), and the alpha-antagonist, phentolamine (150 micrograms icv), and partially reversed the effects of atropine (2.5 mg/kg sc) and the dopamine antagonist haloperidol (0.5 mg/kg sc). The opiate antagonist naloxone (10 mg/kg sc) suppressed tail-pinch-induced eating, and this effect could not be reversed by the GABA-agonist muscimol (500 ng icv) nor norepinephrine (20 micrograms icv). The putative satiety hormones cholecystokinin-octapeptide (5 micrograms/kg sc) and bombesin (5 micrograms/kg sc) suppressed stress-induced eating. The suppressive effect of these substances was reversed by a number of known appetite stimulants viz., D-Ala2-Met-enkephalinamide, diazepam, muscimol, and propanolol. Norepinephrine reversed the suppressive effect of bombesin but not that of cholecystokinin. Based on these results we present a hypothetical model to partially explain the peptidergic-monoamine regulation of stress-induced eating.

Animals↗

Muscimol induces gastric acid secretion after central administration.

Intracerebroventricular administration of the GABA agonist, muscimol, resulted in a dose-dependent increase in gastric acid secretion in pylorus ligated rats. The maximum increase in gastric acid secretion occurred in the second hour. The GABA antagonist, bicuculline methiodide, reversed the muscimol effect on gastric acid secretion. Intracerebroventricular administration of D-alanine methionine enkephalin, bombesin and calcitonin significantly suppressed the muscimol-induced gastric acid secretion. The present study suggests that the GABAergic system plays a role in the central control of gastric acid secretion.

Animals↗

Reproductive events and family history as risk factors for breast cancer in northern Alberta.

Reproductive events and family history as risk factors for breast cancer in northern Alberta were investigated with the use of data from a computerized population-based registry. Women aged 30 to 79 years attending diagnostic breast clinics at the Cross Cancer Institute from 1971 through 1975 constituted the two study groups; 1232 women had diagnosed breast cancer (malignant disease group) and 602 women were clinically free of all types of breast disease (control group). An increased relative risk of breast cancer was found in women with a family history of breast cancer, those who gave birth to their first term infant at age 30 years or older, those in whom more than 15 years elapsed between menarche and that birth, and those with a late natural menopause. There was a decreased risk, relative to nulliparity, in the postmenopausal women who first gave birth to a term infant 5 years or less after menarche. Artificial menopause (bilateral oophorectomy), parity and age at menarche had no apparent effect on the risk. The pattern of risk factors in northern Alberta differed from that reported for other geographic areas, including other provinces of Canada, thus emphasizing the need for local studies in the planning of screening programs.

Adult↗