The serum level of pepsinogen I (PG I) and pepsinogen II (PG II), and the PG I/PG II ratio were compared with the surface area of the fundic mucosa, as determined endoscopically by the Congo red staining method. Reduction in the area of the fundic mucosa due to gastritis was associated with stepwise reduction in the PG I levels and the PG I/PG II ratios. Reduction in the area of the fundic mucosa was also associated with decreases in the basal acid output, maximal acid output (MAO), the basal pepsin output and the stimulated pepsin output. The best sensitivity and specificity levels for the diagnosis of normal mucosa and severe gastritis were obtained with the PG I/PG II ratio and the MAO. A retrospective study of 58 patients with gastric cancer and 162 cancer-free patients showed that a PG I/PG II ratio identified 86.2% of all carcinomas and 87.5% of early carcinomas. Although this test gave a positive rate of 36% among the cancer-susceptible age group controls, its use would lower the cost of mass screening by targeting a smaller test population.
These experiments examined the hypothesis that isolation-rearing and strain influence hedonic mechanisms. In experiment 1, voluntary consumption of ethanol and water was monitored in the home cage of Fawn Hooded (FH) and Wistar rats. FH rats were found to consume more ethanol at low concentrations than Wistar rats, independent of rearing condition, and isolation-reared rats were found to consume more of high ethanol concentrations, independent of strain. In experiment 2, isolation-reared rats were found to consume more sucrose, independent of concentration, than socially reared rats. In experiment 3, Fawn Hooded rats were found to be more sensitive to low concentration solutions of saccharin, and to consume less of the high concentration solutions, while isolation-rearing was found to enhance consumption of high concentrations. Thus, hedonic processes are independently modulated by strain and rearing conditions, although the effects of isolation-rearing appear to be exacerbated in Fawn Hooded rats.
Bombesin-related peptides have a large number of physiological functions as well as having an autocrine growth mechanism for the regulation of small cell lung cancer cells. In the present study we have synthesized 21 des-Met amide or alkylamide analogues of bombesin and compared their abilities to function as bombesin receptor antagonists in guinea pig pancreatic acini and Swiss 3T3 cells with those of the previously most potent antagonist described, [Leu13 psi(CH2NH)Leu14]bombesin (analogue I). All des-Met analogues functioned as antagonists. Bn(1-13)NH2 was approximately equipotent to I (Ki = 60-80 nM) whereas Bn(6-13)NH2 was 30-fold less potent (Ki = 1800 nM). Formation of an ethylamide, Bn(6-13)ethylamide, increased the potency 30-fold such that this octapeptide was equipotent to I. The addition of a D-Phe6 moiety to I did not change potency but caused a 30-fold increase in potency of Bn(6-13)NH2 and a 8-fold increase in the potency of Bn(6-13)ethylamide (Ki = 16 nM). Additional studies of both NH2- and COOH-terminal alterations in Bn(6-13)NH2 demonstrated that the most potent antagonist was [D-Phe6]Bn(6-13)propylamide (PA), having IC50's of 1.6 nM and 0.8 nM for bombesin-stimulated amylase release and Swiss 3T3 cell growth, respectively. Detailed studies of the most potent amide analogue, [D-Phe6]Bn(6-13)NH2, and alkylamide analogue, [D-Phe6]Bn(6-13)PA, demonstrated that these analogues functioned as competitive antagonists and that their action was selective for the bombesin receptor. These results demonstrate that, as with CCK- and gastrin-related peptides, the C-terminal amino acid is important for initiating a biologic response but not essential for determining receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
Voluntary ethanol (EtOH) consumption is increased by isolation-rearing in several rat strains. The following experiments examined the effects of isolation-rearing on basal and ethanol-stimulated behavior in Fawn Hooded rats, an alcohol-preferring rat strain, compared to Wistar rats. Locomotor activity and anxiety were examined under both conditions. Basal locomotor activity was higher in isolated subjects of both strains in low light conditions, but under bright light conditions, this difference was only observed in Wistar rats. Locomotor stimulant effects of EtOH were only observed in isolation-reared rats. In the elevated plus maze, Fawn Hooded rats were more anxious than Wistar rats under low light conditions, but under bright light conditions, Wistar socials were less anxious than all of the other groups. Administration of 1.5 mg/kg EtOH produced an anxiolytic response in the elevated plus maze under bright light conditions in Fawn Hooded rats, but to a lesser degree Wistar rats, particularly Wistar isolates. In conclusion, although both strain and isolation-rearing had effects on locomotion and anxiety as well as the stimulatory and anxiolytic effects of EtOH, these effects appeared to be independent.
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