Biomedical subjects

T Lehy

Publications and source records attributed to T Lehy.

At least 55 records · Page 3Linked to original sources

PubMed1990

Promoting effect of bombesin on the cell proliferation in the rat endocrine pancreas during the early postnatal period.

The present work investigated whether orally administered bombesin influences cell proliferation in the endocrine pancreatic islets of rats during the suckling period and after weaning. Four series of pups were given bombesin diluted in milk (20 micrograms/kg, 3 times daily) or milk alone for 5 days during either the first, second, third or fourth postnatal week of life. Oral administration was used because bombesin-like peptides have been identified in the breast milk of mammals. 45 min before death, animals were given a single [3H]thymidine pulse injection. Tissue sections were processed for radioautography; DNA labeling and mitotic indices were estimated after counting at least 1000 endocrine cells per rat pancreas. In control rats, the labeling and mitotic indices in pancreatic islets dropped regularly from the first week to the fourth week of life (3.6% +/- 0.2% versus 1.9% +/- 0.1% and 0.46% +/- 0.09% versus 0.08% +/- 0.02%, respectively). Orogastric bombesin administration significantly increased the DNA labeling and mitotic indices at the end of the first week (+20% and +62%, respectively) and second week of life (+37.5% and +49%, respectively) (P less than 0.05 to P less than 0.005), but did not modify these parameters for the third and subsequent weeks of life. Therefore, this study provides evidence that bombesin stimulates DNA synthesis and cell division in pancreatic endocrine cells during the developmental period.

Animals↗

PubMed1989

Growth pattern of the polypeptide-YY cell population in the upper digestive tract of the rat during the perinatal period and after weaning.

The distribution of polypeptide-YY cells within the gastric and duodenal mucosa of the rat and the development of their populations were examined daily from 3 days before birth until day 8 postpartum and after weaning, on day 25 postpartum, using a precise technique of quantification. Polypeptide-YY cells appeared in the stomach around the 19th day of gestation. They were always more numerous in the antral mucosa and particularly in the pyloric sphincter area than in the fundic mucosa. Immunogold staining at the electron-microscopic level revealed that, in the antrum, polypeptide-YY was colocalised with gastrin in endocrine cells mainly of type G and, more rarely, in cells of intestinal type IG. Comparison of the gastrin and polypeptide-YY cell populations in the same rats indicated that, except at day 6 postpartum, there were fewer gastric polypeptide-YY cells than immunoreactive gastrin cells and that polypeptide-YY cells were 8 times less numerous than gastrin cells at day 25 postpartum. Polypeptide-YY cells were clearly present in the duodenum of the 19-day-old embryo. This population increases with age until day 8 postpartum, then significantly decreases (by 87%) between days 8 and 25 postpartum. Because polypeptide-YY may inhibit secretion of gastric acid, it is possible that the presence of significant population of polypeptide-YY cells in the upper digestive tract during the first postnatal week of life may play a role (endocrine or paracrine) in the decreased acid secretion occurring in the newborn rat.

Animals↗

PubMed1989

Gastric endocrine cell behavior in Zollinger-Ellison patients upon long-term potent antisecretory treatment.

Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time. Fifteen patients had iterative biopsies. Twenty-one subjects with normal endoscopy, serum gastrin, and acid secretion served as controls. Individual fundic argyrophil cell density was above the highest control value in 77% of the patients, whatever the treatment. Argyrophil cell densities tended to be higher in women than in men. During the survey, fundic carcinoids developed in one ranitidine- and in one omeprazole-treated patient. Fundic argyrophil cell densities were correlated with serum gastrin levels (r' = 0.730, p less than 0.001). Antral somatostatin cell density was not modified in any patients as compared with controls, nor was antral gastrin cell density except in omeprazole-treated patients. In these patients, gastrin cell density and gastrin to somatostatin cell ratio were significantly higher than in all other patients or controls. Such increases may indicate true gastrin cell hyperplasia in relation to drug-induced profound acid inhibition.

Adult↗

PubMed1989

Bombesin ingestion stimulates epithelial digestive cell proliferation in suckling rats.

The characterization of a bombesin-like peptide in the breast milk of some mammals might suggest that this peptide may influence, in part, the postnatal development of the digestive tract. To test this hypothesis, our experiments investigated whether oral administration of bombesin affects epithelial progenitor cell proliferation in digestive organs of suckling and weaned rats. Four series of pups were given bombesin diluted in milk (20 micrograms/kg, 3 times daily) or milk alone, for 5 days during either the first, second, third, or fourth week of life. Pups were killed after [3H]thymidine pulse labeling. DNA labeling and mitotic indices were estimated in the oxyntic, antral, colonic mucosae, and exocrine pancreas. In all tissues examined, oral bombesin significantly increased over control values the two cell proliferative parameters studied during the suckling period (P less than 0.05 to P less than 0.001). In bombesin-treated rats, maximal stimulation of these parameters occurred in the second week of life. This effect of oral bombesin on the cell kinetics disappeared in all tissues after weaning. This study confirms the growth-promoting effect of bombesin observed on the digestive system of the neonatal rat after subcutaneous administration of the peptide and shows that bombesin, when given orally to suckling rats, is sufficiently resistant to proteolysis to enable it to exert a stimulatory effect on digestive cell proliferation. However, our findings as such do not prove that milk bombesin-like peptide has a physiological influence on the developing gastrointestinal tract and pancreas.

Aging↗

PubMed1989

Gastrin processing in primary culture of gastrinoma cells.

There is a general agreement on the cell specificity of gastrin processing. In order to investigate this processing in Zollinger-Ellison (ZE) patients, we have studied in two primary gastrinoma cultures (one from a pancreatic tumor, the other from a liver metastasis) the proportion of progastrin fragments using immunochemical and immunohistological methods. In tumor extracts as well as in sera, the predominant gastrin form differed between the two patients (i.e. being G17 and G34, respectively). In the two gastrinoma cultures, RIA determinations and electron microscopic observations indicated that the proportion of progastrin increased with time while that of G17 and G34 decreased. On the other hand, as the culture time extended, an increasing proportion of nonimmunostained secretory granules was observed suggesting the presence of other gastrin precursors (e.g. Gly-extended progastrin). From these findings, we suggest that gastrinoma culture cells could be a valuable tool in the biochemical approach to gastrin processing in ZE tumors.

Cells, Cultured↗

PubMed1989

Immunohistochemical characterization of gastrinomas with antibodies specific to different fragments of progastrin.

The characterization of the tumors and their metastasis in patients with the Zollinger-Ellison syndrome is currently based on the immunohistochemical identification of gastrin cells. However, sometimes tumoral cells fail to react with common C-terminal gastrin antibodies. In order to clarify this failure, we carried out morphologic, morphometric and immunocytochemical analyses performed on light and electron microscope levels of 6 pancreatic and 1 metastatic gastrinomas, using antibodies raised against various sequences of human progastrin. On the basis, in light microscopy, of qualitative analysis of immunostaining within cells and of immunostained cell numbers, gastrin 34 residue seemed to be the prominent form in 2 of the tumor tissues, G-17 in 1 tumor which was not responsive with C terminus progastrin and N terminus G-34 antisera, and progastrin in the metastatic tissue that did not contain typical gastrin (G-like) cells. Two tumors failed to react with all antisera used. At the electron microscope level, immunogold staining revealed that progastrin was present only in the progranules and gastrin 34 in both progranules and intermediate granules. Quantitative studies performed on 3 tumors showed that, within a given tumoral cell, about 25 percent of progranules contained progastrin while 75 percent contained gastrin 34. We concluded that different forms of gastrin can be immunodetected in a gastrinoma tissue, depending on the regions, and that the distribution of progastrin fragments is variable from tumor to tumor. So, specific antibodies to different fragments of progastrin may help to the characterization of gastrinomas.

Antibodies↗

PubMed1988

Oral administration of epidermal growth factor in suckling rats stimulates cell DNA synthesis in fundic and antral gastric mucosae as well as in intestinal mucosa and pancreas.

The effect of orogastrically given epidermal growth factor (EGF) on the on the development of the digestive system was examined in suckling rats. In particular, DNA synthesis in progenitor cells of the fundic, antral and ileal mucosae and of the exocrine pancreas was analyzed through tritiated thymidine injection and histoautoradiographic study. EGF (10 or 100 micrograms/kg, 3 times daily) was instilled in pups between the 11th and the 13th day of life. Controls received distilled water in a similar manner. All rats were killed 14th after the last orogastric instillation and 45 min after one pulse injection of tritiated thymidine. The highest dose of EGF increased the antral mucosal height (P less than 0.005), the mean number of epithelial cells per crypt column in ileal mucosa, as well as the cell labeling indices of fundic, antral, ileal mucosae and of pancreatic acinar tissue (P less than 0.001) as compared with controls. The lowest dose of EGF increased the cell labeling indices of antral and ileal mucosae and of the exocrine pancreas (P less than 0.001) but did not modify that of fundic mucosa as compared with controls. It is concluded that (a) orally given EGF stimulates cell proliferation in the digestive system of suckling rats, (b) antral mucosa is more sensitive to EGF than fundic mucosa, (c) it is likely that EGF is absorbed and acts systemically on the pancreas. It remains to be determined whether EGF acts systemically or by activation of luminal receptors, on fundic, antral and ileal mucosae.

Administration, Oral↗

PubMed1988

Action of somatostatin analogue (SMS 201-995) on the growth-promoting effect resulting from sustained achlorhydria in rat gastric mucosa, with special reference to endocrine cell behaviour.

We investigated whether a new long-acting somatostatin analogue (SMS 201-995) could antagonize the trophic effect induced by hypergastrinaemia, resulting from chronic omeprazole treatment, on the rat gastric mucosa and particularly on endocrine cell growth. SMS was administered concomitantly with omeprazole for 70 days. Gastric morphometric and cell proliferative parameters, gastric acid secretion and plasma gastrin levels were examined. New findings with omeprazole pointed out: (i) a trophic effect on the antral mucosa and (ii) that the increase observed in gastrin cell number was not due to stimulation of gastrin cell production by omeprazole but more likely to a prolongation of the gastrin cells' life span. As compared to omeprazole alone, simultaneous SMS administration significantly decreased the parietal cell (P less than 0.05) and gastrin cell (P less than 0.01) labelling indices, mucosal height of total glandular stomach (P less than 0.05) and antral mucosal height (P less than 0.05). It tended to lower fundic mucosal height and fundic argyrophil cell density (P less than 0.2 and P less than 0.1, respectively). SMS, in our conditions, did not accentuate the inhibitory effect of omeprazole on gastric acid secretion nor reduce high plasma gastrin levels. We conclude that SMS modestly counteracts the growth-promoting effect observed in rat gastric mucosa after prolonged omeprazole treatment.

Achlorhydria↗

PubMed1988

Influence of bombesin on gastrointestinal and pancreatic cell growth in adult and suckling animals.

Chronic administration of bombesin in the adult rat affects cell growth and enzyme activities in the pancreas. It also induces hyperplasia of the fundic mucosa, increases antral gastrin content, and stimulates gastrin cell proliferation in the antral mucosa. These effects could be explained by the release of hormones such as gastrin and CCK, whose trophic roles on the digestive tract are well proven. Some arguments raise the possibility that bombesin may also act directly on these organs (i.e., the presence of specific receptors for bombesin, pancreatic changes induced by bombesin and not blocked by a potent, specific CCK receptor antagonist). It may well be that both mechanisms exist simultaneously. In addition, bombesin has a growth-promoting effect on the gastric mucosa and pancreas of suckling rats when administered either subcutaneously or orogastrically. Keeping in mind that the maternal milk contains a bombesin-like immunoreactant peptide, we consider that the latter finding raises questions about the possible physiological role of such a peptide in the regulation of the postnatal development of the gastrointestinal tract.

Animals↗

PubMed1988

Gastrin secretion by gastrinoma cells in long-term culture.

Gastrinoma cells from surgical specimens of a primary pancreatic tumor and an hepatic metastasis in two patients with a Zollinger-Ellison syndrome were grown and subcultured for 7 mo. Cultured cells displayed a strong reactivity to heptadecapeptide gastrin antibody and maintained an ultrastructural appearance resembling that of the original tumor cells with the presence of secretory granules of variable size and electron density. Cultured cells also showed the ability to secrete immunoreactive gastrin, and this secretion was further concentration-dependently stimulated by secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin (10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than 0.05). This stimulation occurred in the absence of extracellular Ca2+ and was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin analogue, somatostatin-(201-995), did not alter basal gastrin release but inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP (10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early time intervals of incubation. Furthermore the phorbol ester derivative, 12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin release (10 times the basal value). We conclude that gastrinoma cells can be cultured over an extended period with maintenance of their capacity to secrete gastrin in response to various hormones and mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Bombesin↗

PubMed1988

Influence of hydrocortisone on the development of the gastric mucosa in suckling rats. Inhibitory effect on gastrin cell population.

The effect of a 6-day hydrocortisone administration on the development of gastric mucosa was investigated in suckling rats. Three doses of hydrocortisone (40, 20 and 5 mg/kg/day) were given during the 2nd week of life. Gastric morphometric parameters, and exocrine parietal cell and endocrine gastrin cell numbers were examined and gastrin content in antral tissue was determined. At the end of hydrocortisone treatment, parietal and chief cells were well differentiated. Their larger size was marked in comparison with controls, which likely explains in itself the significant increase in gastric mucosal height. Only the highest dose significantly increased antral gastrin content over control values. However, hydrocortisone, whatever the dose, reduced the apparent antral gastrin cell population by about 60% (p less than 0.001), without noticeably modifying the numerical density of parietal cells per unit of fundic surface. It is nevertheless likely that the highest dose diminished total parietal cell number since the gastric surface decreased. These results suggest that glucocorticoids affect the development of the gastrin cell population while greatly accelerating the maturation of these cells during the suckling period.

Animals↗

PubMed1988

Influence of hydrocortisone on the development of pancreas in suckling rats. Ultrastructural morphometric and biochemical studies.

The effect of hydrocortisone on the growth and differentiation of the pancreas was examined in suckling rats. Three doses of hydrocortisone (40, 20, 5 mg/kg/day) were administered during the second week of life. Biochemical and ultrastructural morphometric studies were performed on the pancreas at the end of the treatment. Whatever the dose used, hydrocortisone induced pancreatic hypertrophy and significantly increased enzymatic activities by 70-200% for lipase and colipase, 140-340% for trypsinogen and chymotrypsinogen and 600-1,200% for amylase. With the 20-mg/kg/day dose, ultrastructural morphometric data indicated that the increase in pancreatic weight was associated with cellular exocrine hypotrophy (diminution of cell size, and of the number of zymogen granules). They also suggest that hydrocortisone, at that dose, might enhance the excretion of secretory products. By contrast, the 5-mg/kg/day dose of hydrocortisone did not modify the acinar cell size, but significantly increased the number of granules per cell. The increase in pancreatic weight and the fact that either cellular hypotrophy or no change in acinar cell size was observed, strongly suggest that hyperplasia occurred with both doses. These results confirm that hydrocortisone is an important modulator of pancreatic development in the rat, inducing stimulation of pancreatic activities, associated with modifications in cell structure and components which vary according to the dose.

Aging↗

PubMed1987

Development of gastric argyrophil carcinoid tumors in a case of Zollinger-Ellison syndrome with primary hyperparathyroidism during long-term antisecretory treatment.

Fundic argyrophil carcinoid tumors developed in the course of a 5-year continuous treatment with high dosages of H2-antagonists in a well-documented case of Zollinger-Ellison syndrome with primary hyperparathyroidism, high basal acid output, and serum gastrin. Approximately 100 small polyps were disseminated throughout the gastric fundus exclusively, leading to total gastrectomy. Metastatic carcinoid in a lymph node and pancreatic gastrinomas also were found at surgery. Gastric endocrine cell proliferation varied from simple argyrophil cell hyperplasia to carcinoid tumors eroding the surface and infiltrating the submucosa. Ultrastructural studies showed that the tumoral proliferation was heterogeneous, and included tumors composed of enterochromaffin (EC) and typical enterochromaffin-like (EC-L) cells, and tumors in which a majority of cells exhibited dense round granules resembling those of A-like or D1/P endocrine cell types. The risk of developing gastric fundic carcinoid tumors in ZES patients submitted to long-term antisecretory treatment should be given increased attention.

Carcinoid Tumor↗

PubMed1987

Comparative development of gastrin and somatostatin cell populations in the pancreas, stomach, and duodenum of the rat during the perinatal period.

The comparative growth patterns of endocrine gastrin and somatostatin cell populations were examined in the rat, during the perinatal period, to investigate possible relationships between their development and that of gastric acid secretion, gastrin and somatostatin hormones being implicated in the regulation of acid secretion. Total cell populations were estimated daily in the pancreas, stomach, and duodenum, by using a quantitative morphological method, from 19 days postcoitum to 8 days postpartum. In the pancreas, both cell types were present at 19 days postcoitum. After increasing, gastrin cells abruptly dropped from 4 days postpartum, while somatostatin cells continued to increase. In the stomach, gastrin cells seemed to appear at 19 days postcoitum, increasing with age. Somatostatin cells appeared only after birth and could be precisely quantified from 4 days postpartum. In the duodenum, the two cell types were present in similar numbers at 19 days postcoitum and increased similarly with age. Comparison of gastrin and somatostatin cell developmental behavior with previous data on the ontogeny of acid secretion shows a parallelism between the appearance of basal H+ fluxes at 20-21 days postcoitum and the high daily multiplication of the gastrin cell number in the three organs. Additionally, the marked decrease of pancreatic gastrin cell population at 4 days postpartum and the simultaneous development of the gastric somatostatin cell population might explain, among other mechanisms, the diminution of gastric acid secretion noted after birth.

Age Factors↗

PubMed1986

Stimulating effect of bombesin on the growth of gastrointestinal tract and pancreas in suckling rats.

The current study examines the effects of bombesin on gastrointestinal and pancreatic growth in suckling rats. During a period of 6 days, 7-day-old rats were injected twice daily with bombesin tetradecapeptide (20 micrograms/kg) in hydrolyzed gelatin or with gelatin alone. At the end of bombesin treatment, the weights of stomach, intestine, and pancreas; the heights of fundic and antral mucosae; and the density of parietal cells were significantly increased over control values. The gastrin cell population also tended to be augmented. The surface of glandular stomach, the duodenal mucosal height, and the somatostatin cell population were not modified as compared to controls. Electron morphometric analysis indicates that the increase in pancreatic weight under bombesin treatment was partly due to hypertrophy of acinar cells. This was confirmed by biochemical data that also showed that hypertrophy was associated with hyperplasia. Storage of secretory granules in acinar cells of the neonate rat pancreas under bombesin treatment seemed probable. Chymotrypsinogen and trypsinogen pancreatic contents were greatly augmented; lipase and colipase contents were not affected, whereas the amylase content tended to decrease. All these findings suggest that bombesin might be a general trophic factor for the neonatal digestive system in the rat. The mechanism of its action, however, remains to be determined.

Animals↗

PubMed1986

Growth hormone-releasing factor (somatocrinin) stimulates epithelial cell proliferation in the rat digestive tract.

The possible influence of growth hormone-releasing factor (GHRF) on epithelial cell proliferation in the digestive tract was investigated. Fasted young rats received five hourly subcutaneous injections of either GHRF or saline. They were killed 6, 12, or 18 h after the initial injection and 45 min after [3H]thymidine pulse labeling. At the time of death, blood was taken to determine circulating growth hormone and gastrin levels. After radioautography, DNA synthetic and mitotic activities were estimated in the fundic, antral, duodenal, jejunal, and colonic mucosae. Growth hormone-releasing factor significantly increased labeling indices 6, 12, and 18 h after the initial injection in fundic mucosa, and 6 and 18 h after injection in antral and duodenal mucosae. Furthermore, GHRF significantly increased mitotic indices at 12 h in fundic mucosa and at 12 and 18 h in jejunal mucosa. No effect was seen in the colon. At the three checkpoint times, circulating growth hormone showed no change, but plasma gastrin was increased in the rats treated with GHRF as compared with controls. However, whether the reported stimulatory effect of the GHRF on target cells is direct or indirect remains to be determined.

Animals↗

PubMed1986

Antral gastrin- and somatostatin-producing cells and intraluminal peptide secretion in normal subjects and duodenal ulcer patients with and without vagotomy.

The behaviour of gastrin (G) cells and somatostatin (D) cells in endoscopic antral biopsies and that of intraluminal gastrin (ILG) and somatostatin (ILS) release in the gastric juice were investigated in three groups of patients: control subjects, duodenal ulcer (DU) patients and DU patients treated by a superselective vagotomy (SSV). G and D cell densities were correlated in the three groups of subjects. The G/D cell ratio was significantly increased in SSV patients (P less than 0.001) as compared to control and DU patients. No correlation was found between gastrin or somatostatin cell densities and basal intraluminal levels of the two peptides. ILG output was significantly higher in DU patients than in control or SSV patients (P less than 0.001). ILS output was also higher in DU patients than in controls (P less than 0.001) and in SSV patients (P less than 0.05). It was also significantly augmented in SSV (P less than 0.001) as compared to control patients. ILG and ILS concentrations were only correlated in controls. Within each of the three groups of subjects, ILG and ILS release varied in function of the gastric juice pH. Our results emphasize the necessity to consider the intragastric pH as well as the physiological or pathological state to study intraluminal peptides in man.

Adolescent↗

PubMed1986

Growth hormone releasing hormone stimulates the release of gastrin in rat.

The inhibitory effect of somatostatin on gastrin release is well known. Could the growth hormone releasing hormone (GHRH), an antagonist of somatostatin on growth hormone (GH) release, have a gastrin-releasing effect on gastrin? To answer this question, two types of experiments were conducted: (1) The study of the effect of GHRH on gastrin in rats, which showed a significant and dose related release for the three doses studied: 0.12, 0.6 and 3.0 micrograms/rat. (2) The study on the recurrence of this gastrin releasing effect which has been found to be significant (1 to 5 injections at 1 hour intervals). Our data suggest that GHRH is an hypothalamic releasing factor for gastrin release. Accordingly, gastrin may mediate the observed proliferative effect of GHRH in the upper digestive tract.

Animals↗