Search PubMed⌕ Search

Biomedical subjects

L R Johnson

Publications and source records attributed to L R Johnson.

At least 217 records · Page 12Linked to original sources
PubMed1981

Mucosal gastrin receptor. V. Development in newborn rats.

We determined the development of the oxyntic gland mucosal gastrin receptor in rats killed at various times from 5 to 60 days after birth. Rats were weaned on the 18th day after birth. Newborn animals had no detectable gastrin binding, high serum gastrin levels (800-1,200 pg/ml), low antral gastrin levels (0.5-2.0 micrograms/g tissue), or high pH of gastric contents (pH greater than 5.0) and did not respond to pentagastrin. At the time of weaning, serum gastrin dropped to 600 pg/ml and reached adult levels (300 pg/ml) on day 40. Antral gastrin increased to 7.5 micrograms/g tissue on day 20 and reached adult levels (20 micrograms/g tissue) on day 22. Specific binding of gastrin was first detected on day 20 and reached the adult level of 4 fmol/mg protein on day 60. Pentagastrin significantly stimulated acid secretion on day 20 and DNA synthesis on day 25. Prevention of weaning through day 25 decreased the magnitude but did not prevent or delay the onset of the above changes. These results indicate that 1) the absence of a gastrin response in newborn rats is due to a lack of gastrin receptors, 2) development of gastrin receptor and biological sensitivity to gastrin appear at the time of weaning, and 3) the development that occurs with weaning is enhanced but not triggered by the shift to solid food.

Aging↗
PubMed1981

Mucosal gastrin receptor. VI. Induction by corticosterone in newborn rats.

Serum and antral gastrin levels as well as specific binding of [125I]gastrin-17 to a 270-30,000 g oxyntic gland mucosa crude membrane preparation were measured in rats between 5 and 40 days of age. Rats were normally weaned at day 18, although weaning was prevented in some animals until day 25. The results of these studies confirmed our previous data showing that mucosal gastrin receptors and antral gastrin levels begin to increase at the time of normal weaning and reach adult levels within a few days. Although the shift from liquid to a solid diet enhances the response, it is not essential for it and does not trigger it. In addition, the current studies demonstrated that injection of corticosterone caused a premature increase in both gastrin receptor and antral gastrin levels. Once maturation had occurred, however, corticosterone had no further effect. Adrenalectomy delayed but did not prevent the maturational changes in gastrin receptors and antral gastrin levels. Normal serum gastrin concentrations were necessary for the number of gastrin receptors and the amount of antral gastrin to reach normal levels.

Adrenalectomy↗
PubMed1981

Diaphragm paralysis and ventilatory failure in chronic proximal spinal muscular atrophy.

Ventilatory failure occurred in a patient suffering from proximal neurogenic muscular atrophy resembling the adult form of Kugelberg-Welander syndrome. Diaphragmatic paralysis was diagnosed when patient was found to be unable to generate a transdiaphragmatic pressure difference on deep inspiration. Post-mortem examination revealed nearly complete replacement of the diaphragm by fat and fibrous tissue. Although uncommonly reported in the medical literature, ventilatory failure secondary to diaphragm dysfunction should be added to the list of complications encountered in the clinical setting of chronic proximal spinal muscular atrophy.

Adult↗
PubMed1981

Effect of dietary bulk on small intestinal morphology and cell renewal in the rat.

Feeding an elemental diet (Vivonex) to rats over 9 days causes a decrease in the rate of cell renewal and a reduction in villus size in both the jejunum and ileum, as compared with rats fed regular chow. The addition of bulk to elemental diet cannot prevent the reduction in villous size, but it can cause a small increase in the rate of cell renewal, which is still much lower than that in chow-fed rats. The serum gastrin level of rats fed the elemental diet is about one-third of the level found in chow-fed rats, and it is not changed by the addition of bulk.

Animals↗
PubMed1980

Brain stem degeneration patterns following tooth extractions: visualization of dental and periodontal afferents.

The terminal central nervous system distribution of those primary afferent neurons from the teeth and periodontium in cats was studied by degeneration methods. Lesions were created by combinations of tooth extractions and the brain stem was examined at 14, 30 and 60 days survival for degeneration patterns, with 30 days being the optimal survival time. Degenerating axons and terminals are seen bilaterally, but somewhat less on the side contralateral to the lesions and are concentrated in the ventral half of pars interpolaris and pars caudalis near obex. The results are discussed with regard to the current controversies concerning the primary central termination of these trigeminal neurons.

Afferent Pathways↗
PubMed1980

Influence of method of feeding on stress ulcer development in the rat.

Maintenance of rats on total parenteral nutrition for 10 days increased the susceptibility of these animals to gastric ulceration and death due to cold-temperature restraint stress. Animals fed the identical diet orally were much less susceptible. Serum gastrin concentrations were increased by stress in both groups of animals despite initially low serum levels. Glucosamine synthetase specific activity was not altered by the method of feeding but tended to be decreased by restraint. These results suggest that orally administered food protects the animal from stress-induced damage by a mechanism(s) involving neither dietary composition nor gastrin.

Animals↗
PubMed1980

Stimulation of rat oxyntic gland mucosal growth by epidermal growth factor.

Epidermal growth factor (EGF) inhibits gastric acid secretion, but its effects on the growth of gut mucosa have not been examined. Fasted male rats were given six injections of EGF (10 micrograms/kg) over a 48-h period. The animals were killed and the incorporation of [3H]thymidine into various tissues was examined and compared to rats treated with NaCl, pentagastrin, and EGF plus secretin. EGF and pentagastrin significantly increased DNA synthesis of the oxyntic gland mucosa. Pentagastrin, but not EGF, stimulated DNA synthesis of duodenal and colonic mucosa as well. Neither peptide altered skin DNA synthesis. Secretin inhibited the effects of pentagastrin but not EGF. Chronic administration of EGF (5 days) caused significant increases in oxyntic gland mucosal DNA, RNA, and protein content. These results not only demonstrate that EGF is a trophic agent for the oxyntic gland mucosa but lend further support to the hypothesis that acid secretion and mitogenesis are the result of two separate mechanisms.

Animals↗
PubMed1980

Mucosal gastrin receptor. III. Regulation by gastrin.

Specific binding of 125I-labeled gastrin to rat gastric mucosal membranes was found to vary with serum gastrin levels. The dissociation equilibrium constants were not significantly different between receptor preparations. However, the binding capacities of the membrane preparations were directly correlated with serum gastrin levels. Fasting, feeding a liquid diet, and antrectomy significantly decreased serum gastrin and the concentrations of the gastrin receptor. Treatment of fasted and liquid-fed animals with pentagastrin prevented the decrease in receptors. Vagotomy increased both binding capacity and serum gastrin levels. These data indicate that gastrin stimulates the production of its own receptor. The upregulation of the gastrin receptor was evident if the binding capacity was expressed per milligram of protein, per microgram of DNA, or per amount of 125I-labeled choleragen bound to the same membrane preparation. This indicates that the biological response to gastrin is controlled in part by the regulation of the number of gastrin receptors present and that gastrin plays a role in this regulatory process.

Animals↗
PubMed1980

Effect of chemically defined diets on antral and serum gastrin levels in rats.

When rats were fed isocaloric amounts of chemically defined diets with variable amounts of protein (8-60%) or fat (0-30%) over a 10-day period, their serum and antral gastrin concentrations were, respectively, 60 and 40% lower than the levels of chow-fed rats. It was also determined that neither the low bulk content of these diets nor their inability to adequately buffer the gastric pH contributed to this response. The time course of this dietary-induced reduction in gastrin levels was investigated and it was found that the serum hormone levels were significantly reduced as early as 1-2 h after chow-fed rats were placed on these chemically defined diets. Antral gastrin levels were maintained at normal levels for 4-5 days after rats started consuming these synthetic diets and fell thereafter. With all of the chemically defined diets tested, the gastrin secretory response to a meal was significantly reduced. It therefore appears that synthetic diets lack some undefined food constituent present in chow that is required for the normal postprandial release of gastrin or, alternatively, that they contain an inhibitory factor which blocks the normal secretory response.

Animals↗
PubMed1980

Isolated parietal cells: [3H]QNB binding to putative cholinergic receptors.

The tritiated muscarinic cholinergic antagonist quinuclidinyl benzilate, [3H]QNB, was used as a direct probe for the detection and characterization of muscarinic cholinergic receptors associated with the particulate fraction of isolated and purified rat gastric muscosal parietal cells. Specific binding is saturable (Bmax = 55 fmol/mg protein, KD = 0.78 nM), shows a single population of binding sites, and has appropriate pharmacological specificity. Nanomolar concentrations of muscarinic cholinergic antagonists, such as atropine and scopolamine, inhibit [3H]QNB binding by 50%, whereas micromolar concentrations are needed for agonists, such as acetylcholine, oxotremorine, and carbamylcholine. Binding is also stereoselective as shown by the more than 1,000-fold difference in inhibitory potencies of the stereoisomers of benzetimide. Noncholinergic agents, including pentagastrin, histamine, and the H2-receptor antagonists cimetidine and metiamide, have little or no effect on [3H]QNB binding at concentrations of 100 microM. These data support the existence of specific parietal cell muscarinic cholinergic receptors with which the secretagogue acetylcholine may directly interact to initiate gastric acid secretion.

Animals↗
PubMed1980

Mucosal gastrin receptor. IV. Binding specificity.

We used membrane preparations of rat oxyntic gland mucosa to test the binding of various gastrin analogues to the gastrin receptor. Using [125I]15-Leu G-17 as a marker, a concentration of 4 X 10(-9) M unlabeled G-17 inhibited binding 50%. The tetra-, penta-, and hexapeptides of gastrin caused similar 50% inhibitions of binding at concentrations of 1 X 10(-7) M, 3 X 10(-8) M, and 7 X 10(-9) M, respectively. The heptapeptide caused only slightly less inhibition than G-17, whereas the decapeptide was equivalent in potency. Neither the G-17 nor G-34 that had the active tetrapeptide removed caused 50% inhibition of binding. When compared to G-17, these analogues produced only a 25% inhibition of binding at concentrations of 10(-8) M. We also failed to inhibit binding more than 25% when we used an analogue that had the amide removed from the C-terminal phenylalanine. Atropine, metiamide, and mepyramine did not alter the binding of gastrin to receptor. The results of binding specificity approximate the changes in biological potency associated with these compounds. This study adds further support that the gastrin receptor in question is responsible for the physiological effects of the hormone.

Animals↗
PubMed1980

Stimulation of pancreatic growth by intraduodenal amino acids and HCl.

Exogenous secretin and cholecystokinin (CCK) have been shown to stimulate the growth of the exocrine pancreas. To conclude that a hormone produces an effect under normal physiological conditions, one must demonstrate that the endogenous hormone also produces the action in question. To release endogenous secretin 0.01 N HCl was continuously infused into the duodenums of eight rats for 5 days. Sixteen animals were prepared with catheters inserted 1 cm below the pylorus. The other eight animals were infused with PO4 buffer, pH 7.5. The infusion rate for both groups was 2 ml/h. Animals were killed at the end of 5 days, and the oxyntic gland mucosa and pancreas were examined. Pancreatic weights, DNA synthesis, DNa, RNA, and protein content were significantly increased in rats receiving acid. An identical experiment was set up to release endogenous CCK. In this experiment eight rats received a solution containing 50 mM phenylalanine and 50 mM tryptophan. The controls received the caloric equivalent in glucose. At the end of 1 wk the pancreases of the rats infused with amino acids averaged 405 (P < 0.001) heavier than the controls. Similar increases occurred in DNA, RNA, and protein content. These studies suggest that endogenous secretin and CCK can be released in amounts sufficient to stimulate growth.

Amino Acids↗
PubMed1979

Mucosal gastrin receptor. I. Assay standardization and fulfillment of receptor criteria.

Using iodinated gastrin with demonstrable biological activity, this study has shown that optimal specific gastrin binding occurs in rat gastric mucosal 270--30,000 g membrane preparations after an incubation period of 30 min at 30 degrees C (pH 7.4) with a protein concentration of 150--200 micrograms per assay tube. The gastrin binding was shown to be saturable with an equilibrium Ka of approximately 0.25 X 10(10) M-1 and an equilibrium Kd of approximately 4 X 10(10) M. The binding capacity was approximately 4 fmol/mg protein. Specific gastrin binding was shown to be present in the oxyntic gland and duodenal mucosa and to be absent from the antral mucosa, liver, spleen, and kidney. In order to decrease the specific binding of gastrin by 50% the competitors in order of potency are 15-Leu G-17 greater than cholecystokinin greater than caerulein greater than pentagastrin; secretin did not display a response similar to the other four competitors tested, indicating that its inhibition may be non-competitive. Fasting decreased the binding capacity of the gastrin receptor and refeeding brought the receptor levels back to control range; this result parallels the decrease seen in serum gastrin after fasting and the return to normal levels with refeeding. This suggests that rat gastric mucosal gastrin receptors may exhibit autoregulation. This study is the first to meet all the criteria for establishing the existence of a mucosal gastrin receptor.

Animals↗