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Biomedical subjects

L R Johnson

Publications and source records attributed to L R Johnson.

At least 199 records · Page 11Linked to original sources
PubMed1983

Ultrastructural study of transganglionic degeneration following dental lesions.

Transganglionic degeneration in the trigeminal main sensory nucleus (MSN) and pars interpolaris (PI) was studied in cats following dental lesions. At early survival times, three types of terminal alteration were seen in both MSN and PI: (1) flocculent degeneration, (2) neurofilamentous hyperplasia and, (3) glycogen accumulation. With longer survival times, the magnitude of these terminal alterations increases. Electron dense degeneration was only seen in the ventral half of PI. Phagocytosis of the altered terminals was also observed. The study suggests a plausible explanation for the variations observed in the CNS projection of primary afferents with degeneration and with HRP transport studies.

Animals↗
PubMed1983

Development of sensitivity to different secretagogues in the rat stomach.

Acid and pepsin secretion and gastric mucosal histidine decarboxylase activity were measured in rats of various ages between 5 and 40 days after injection of saline, pentagastrin, histamine, or carbachol. Basal acid secretion first appeared on day 15. At this time carbachol significantly stimulated both acid and pepsin secretion. Gastrin and histamine did not stimulate acid or pepsin secretion until day 20. Histidine decarboxylase activity first appeared on day 10 and was first increased by pentagastrin on day 18. Injection of 8-day-old rats with corticosterone prematurely induced acid secretion on day 12 in response to all three stimulants and pepsin secretion in response to carbachol only. These studies provide a comprehensive picture of the development of gastric mucosal sensitivity to the three naturally occurring stimulants and indicate that adrenal glucocorticoids play an important role in that development.

Aging↗
PubMed1983

Contraction and [3H]QNB binding in collagenase isolated fundic smooth muscle cells.

Smooth muscle cells from the guinea pig gastric fundus were isolated by successive collagenase digestions. Tritiated quinuclidinyl benzilate [( 3H]QNB) was used to study the binding characteristics of the muscarinic cholinergic receptors on these cells. Each cell bound 8.3 X 10(-19) mol of QNB, and a concentration of QNB of 0.19 nM was required to label one-half of the binding sites. This suggests a concentration of about 500,000 muscarinic cholinergic receptors per smooth muscle cell. The muscarinic cholinergic receptor antagonists atropine and scopolamine inhibited QNB binding with a 50% inhibiting concentration (IC50) in the nanomolar range, whereas the agonists acetylcholine (ACh), oxotremorine, and carbamylcholine had IC50S in the micromolar range. Hill coefficients (nH) for antagonists approached unity, but agonists displayed fractional nH. Exposure of cells to cholinergic muscarinic agonists resulted in dose-dependent decreases in cell length. The concentration of agonist required to induce half-maximal contractions (ED50) was 8.3 X 10(-12) M for ACh and 6.3 X 10(-13) M for oxotremorine. Atropine (10(-9) M) decreased the sensitivity to ACh, increasing the ED50 for ACh-induced contractions to 1.2 X 10(-10) M. These results suggest the existence of muscarinic receptor heterogeneity for cholinergic agonists but not for antagonists.

Acetylcholine↗
PubMed1983

Regulation of antral gastrin content.

Five groups of rats were fasted for 3 days and injected with either NaCl or 5, 10, 20, or 40 micrograms/kg bombesin every 8 h. The animals were killed, and their serum and antral gastrin levels were compared with those of normally fed rats. Fasting reduced serum gastrin to 14% of control; antral gastrin was reduced to 21% of control. All doses of bombesin significantly increased serum gastrin in fasted rats, and 20 and 40 micrograms/kg significantly increased antral gastrin. A group of normally fed rats was also compared with one fed a liquid diet for 7 days. Half of each of these was injected with 20 micrograms/kg bombesin (3 times/day) and the other half with NaCl. Bombesin significantly increased serum and antral gastrin in the rats fed solid food. The liquid diet lowered serum and antral gastrin to 17 and 59% of control values, respectively. Bombesin injection totally prevented these decreases. These data indicate that food in the gastrointestinal tract is not required for either gastrin release or synthesis. Furthermore, the data suggest that gastrin synthesis is regulated primarily by gastrin release or by direct stimulation by bombesin rather than by specific food products.

Animals↗
PubMed1983

Acute effects of volcanic ash from Mount Saint Helens on lung function in children.

To evaluate the acute effects of volcanic ash from Mt. St. Helens on the lung function of children, we studied 101 children 8 to 13 yr of age who were attending a 2-wk summer camp for children with diabetes mellitus in an area where about 1.2 cm of ash had fallen after the June 12, 1980, eruption. The outcome variables used were forced vital capacity, forced expiratory volume in one second, their ratio and mean transit time. Total and respirable dust levels were measured using personal sampling pumps. The children were tested on arrival and twice (early morning [A.M.] and late afternoon [P.M.]) every second or third day during the session. A within-day effect was measured by the P.M./A.M. ratio for the lung function variables; a between-day effect was measured by the change in the P.M. measurements over the 2 wk of camp. We found no strong evidence of either a within-day or a between-day effect on lung function, even in a subgroup of children who had preexisting lung disease or symptoms, despite daytime dust/ash levels that usually exceeded the Environmental Protection Agency's significant harm level for particulate matter.

Adolescent↗
PubMed1983

Regulation of the mucosal gastrin receptor.

The gastrin receptor in rat oxyntic gland mucosa is highly regulated. This regulation has so far only been found to be directed at the total numbers of receptors present. The affinity of the receptor is not altered significantly by agents which affect receptor numbers. Homospecific regulation occurs in that gastrin upregulates its receptor over long periods of time. Upregulation, however, appears to be preceded by a brief period of downregulation. During development corticosterone triggers the synthesis, or at least the appearance of gastrin receptors. Receptor development is maintained by solid food and presumably the gastrin it releases, but the change in diet which occurs at weaning does not in itself induce development. In female rats, estrogens prevent the increase of gastrin receptor levels to those found in males. These results with the gastrin receptor emphasize the importance of studying receptor concentrations as well as hormone levels to the total understanding of an endocrine response. They also suggest that the receptors of the other gastrointestinal hormones are likely to be regulated and that this regulation will probably be important in understanding some of the diseases of the gastrointestinal tract.

Adrenal Cortex Hormones↗
PubMed1983

Muscarinic cholinergic receptors in the piebald mouse model for Hirschsprung's disease.

The contracted segment of terminal large intestine in both Hirschsprung's disease in humans and in the piebald-lethal strain of mice with congenital megacolon may result from muscarinic cholinergic receptor denervation supersensitivity. This hypothesis was tested by direct binding studies using the muscarinic receptor ligand, tritiated quinuclidinyl benzilate. There were no differences in either the receptor density, dissociation constant, or agonist/antagonist Hill coefficients in the proximal, middle, or distal colon of mice with congenital megacolon as compared with normal littermates. These data do not support the concept of denervation supersensitivity. The data support the suggestion that absence of the inhibitory neurons of the enteric nervous system accounts for the hyperexcitability of the musculature of the aganglionic terminal segment and the obstructive constriction of the segment.

Animals↗
PubMed1982

Distribution of (3H)QNB binding in dog gastric smooth muscle pre- and post vagotomy.

Tritiated quinuclidinyl benzilate [(3H) QNB] was used to characterize muscarinic cholinergic receptors in membrane fragments prepared from the circular smooth muscle of the dog stomach. In preliminary experiments the effect of protein, incubation time, temperature and pH on QNB binding were evaluated. Muscarinic cholinergic antagonists and agonists inhibited QNB binding in a concentration-dependent manner, but the nicotinic antagonist hexamethonium and adrenergic compounds were not effective in displacing QNB from binding sites. Scatchard plot analysis of binding data showed an asymmetric receptor distribution in the stomach. The cardia bound 425fmol of QNB/mg protein with a Kd of 0.05nM, the fundus 267fmol/mg protein with a Kd of 0.09nM and the antrum 147 fmol/mg protein with a Kd of 0.14nM. In a second series of experiments, binding of QNB was measured in dogs which had been vagotomized three weeks earlier. Vagotomy had no effect on the apparent Kd but disrupted the asymmetric receptor distribution seen in the normal dog such that the Bmax of the cardia fell to a value of 222fmol/mg protein.

Animals↗
PubMed1982

Characterization of the interaction between gastrin and its receptor in rat oxyntic gland mucosa.

A gastrin receptor, identified in crude membrane preparations of rat oxyntic gland mucosa, has an equilibrium dissociation constant (Kd) of approx. 4 . 10(-10)M and a binding capacity of 4 fmol/mg protein. The binding capacity was significantly lower after 2 days of fasting, parallel with a significant drop in serum gastrin levels; there was no change in Kd. In order to verify Scatchard analysis and to determine if there was a coincident alteration in the association (k+1) and dissociation (k-1) rates in the fasted rat, a kinetics study was performed. Under our conditions, there appeared to be a single set of binding sites and the binding reaction obeyed first-order dissociation, and second-order association rate kinetics. Second-order association rate kinetics were validated by demonstrating the independence of the rate constants when there were alterations in the concentrations of reactants. The average k+1 was determined to be 2 . 10(6) M-1 . s-1. The average k-1 was determined to be 1 . 10(-3) s-1. There was no significant change in the k+1 and k-1 in fed and fasted rats. Fasting decreased the number of gastrin receptors without altering the affinity of the receptor for the hormone.

Animals↗
PubMed1982

Gastric mucosal cell proliferation during development in rats and effects of pentagastrin.

Changes in cell proliferation and cell loss in the gastric mucosa were examined during the first 4 wk of life. The effect of pentagastrin on these parameters before and after weaning was also investigated. The results revealed that DNA content of mucosa and lumen increased with age. However, when luminal DNA (an assessment of cell loss) content was expressed as percent of total mucosal DNA (referred to as percent cell loss), an inverse relationship with age was observed. The rate of mucosal DNA synthesis, measured in vitro, was found to remain elevated up to the age of 15 days and then dropped dramatically within the next 5--6 days after which it decreased slowly. The rate of mucosal DNA synthesis in 5- to 15-day-old rats was found to be 10--15 times higher than in 20- to 30-day-old rats. In 10-day-old suckling young, mucosal thymidine kinase activity was also found to be higher than in 20- to 28-day-old rats. On the other hand, total incorporation of [3H]thymidine into mucosal DNA per stomach was found to be significantly greater in 21- to 28-day-old weaned rats than in the 10-day-old suckling young. Multiple injections of pentagastrin to 28-day-old rats significantly increased mucosal DNA synthesis and thymidine kinase activity by 43 and 200%, respectively, and cell loss by 30% when compared with the saline control. The hormone did not affect DNA synthesis, thymidine kinase, or cell loss in 10-day-old rats. There were considerable increases in 20-day-old rats that were not statistically significant due to the variation of the data.

Animals↗
PubMed1982

Mucosal gastrin receptor. VII. Up- and downregulation.

A series of experiments were performed to examine the long-term upregulation of the gastrin receptor and to explore the possibility of a short-term down regulation with regard to the time course of the trophic action of gastrin. Vagotomy or fasting was used to examine upregulation. Elevated serum gastrin levels observed postvagotomy are accompanied by an increase in gastrin binding capacity. Conversely, fasting caused a decline in serum gastrin and receptor levels; refeeding restored both values to normal levels. Cycloheximide was used to study the role of protein synthesis in the upregulation of gastrin receptors in vagotomized and refed rats, and it prevented the rise of gastrin binding capacity to either normal or above-normal values. This indicates that protein synthesis may play an integral part of receptor upregulation. Following the injection of gastrin-17, there was a short-term induction of downregulation. These results coupled with the maximal reduction of gastrin receptor 3 h after cycloheximide injection indicate that the gastrin receptor has a short half-life. Following the gastrin receptor interaction, the cellular response occurs at discrete periods and manifests itself as both down- and upregulation.

Animals↗
PubMed1982

Role of gastrin in gastrointestinal adaptation after small bowel resection.

Gastrin is a trophic hormone for the mucosa of the oxyntic gland area of the stomach, the proximal small intestine, and the colon. It also has trophic effects on the pancreas. All these tissues undergo hyperplasia to some extent following distal small bowel resection. This study evaluates the role of gastrin in postresectional hyperplasia by examining the growth of these tissues in antrectomized rats following intestinal resection. Antrectomy itself caused atrophy of the oxyntic gland mucosa, colonic mucosa, and the pancreas but had no effect on ileal mucosa. Resection by itself stimulated growth of all tissues and significantly increased serum gastrin levels. After resection in antrectomized animals, all tissues underwent an adaptational response. The increase in total DNA content after resection in antrectomized rats was as great in all tissues, except the colon, as it was in animals with intact antrums and normal gastrin levels. These results indicate that gastrin plays no role in the postresectional hyperplasia observed in the various tissues of the gastrointestinal tract.

Animals↗
PubMed1982

Mucosal gastrin receptor. VIII. Sex-related differences in binding.

The purpose of the current study was to determine whether gastrin binding differed between the sexes and, if so, to ascertain the factors responsible. Male and female rats were killed at various times from 15 to 60 days after birth. Binding capacities in male and female rats were equal until puberty. By day 40 there were significantly more receptors present in males than females. Females had 2.4 fmol receptor/mg prot by day 40, and this value remained constant into adulthood. In male rats the number of receptors continued to increase to 4.0 fmol/mg prot at day 60. Castration did not significantly decrease the number of receptors in male rats. Ovariectomy, however, increased the number of receptors in female rats to a value not significantly different from male controls. Ovariectomized females consumed more food and had higher serum gastrin levels. If ovariectomized rats were pair fed to the level of intact females, the number of receptors and serum gastrin levels decreased over those present in ovariectomized rats fed ad libitum but still remained significantly higher than those in intact females. Adrenalectomy of ovariectomized females caused a further increase in receptor number.

Adrenalectomy↗
PubMed1982

Effect of exogenous gut hormones on gastrointestinal mucosal growth.

Numerous GI hormones and peptides, such as gastrin, CCK, secretin, glucagon, somatostatin and EGF, have been shown to stimulate at least part of the trophic response in GI tissues. Whether any of these (or a different one) accounts for gastrointestinal adaptation is unknown. Final proof will entail the demonstration that the endogenous serum levels of one of these increases during the adaptation period to amounts significant to cause the response.

Adaptation, Physiological↗
PubMed1981

Effects of gastrointestinal hormones on pancreatic growth.

This article discusses experiments demonstrating that the gastrointestinal hormones, gastrin, secretin, and CCK (cholecystokinin), stimulate the growth of the exocrine pancreas. Exogenous gastrin, secretin, and CCK increase pancreatic weight DNA, RNA and protein content of the rat pancreas. Antrectomy, which removes most endogenous gastrin, decreases pancreatic growth. The effects of antrectomy are prevented by exogenous gastrin. Infusion of HCl into the duodenum to release secretin and infusion of amino acids into the duodenum to release CCK also stimulate pancreatic growth. These results provide evidence that the regulation of pancreatic growth is an important action of the gastrointestinal hormones.

Amino Acids↗