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T Lehy

Publications and source records attributed to T Lehy.

At least 73 records · Page 4Linked to original sources

[Histologic aspect of the human gastric mucosa: relation to gastrin and somatostatin cells and the intraluminal secretion of these peptides].

Fifty-eight subjects including controls, patients with duodenal ulcer, non-operated or treated with a superselective vagotomy underwent endoscopic fundic and antral biopsies. Histologic classification of the two mucosae was performed. We examined the relationship between the histologic grade of gastritis in the two mucosae, then between the histologic aspect of the antral mucosa and antral gastrin-and somatostatin-cell densities, the basal intraluminal secretion of gastrin and somatostatin. There was a significant correlation between the histologic aspect of fundic or antral mucosa and the age of patients, except in the case of vagotomized patients. Fundic and antral histologic patterns were also correlated in each patient, except for vagotomized. Gastrin and somatostatin cell densities showed no variation in function of the degree of inflammation of non atrophic gastritis. These cell densities showed a tendency to decrease in atrophic gastritis, especially when intestinal metaplasia was present. Intraluminal gastrin secretion was increased in patients with mild atrophic gastritis (p less than 0.05 to p less than 0.02) in comparison with those whose histology was roughly normal. It was also increased in severe atrophic gastritis. The highest intraluminal secretion of somatostatin was observed in patients with mild atrophic gastritis while this secretion fell noticeably in those showing severe atrophic gastritis, as compared to the other groups. This work seems to suggest a relationship between intraluminal peptides and the evolution of gastritis. While results are still preliminary, they do not indicate that these peptides, thus released, play any pathophysiologic role.

Adolescent↗

Epithelial cell proliferation in human fundic and antral mucosae. Influence of superselective vagotomy and relationship with gastritis.

Epithelial cell proliferation in the fundic and antral mucosae was studied in 19 duodenal ulcer patients, 11 patients having undergone fundic superselective vagotomy for duodenal ulcer, and 10 controls. This was achieved through in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautography. Except for increased fundic mucosal height, duodenal ulcer patients did not differ from controls for all parameters studied. In vagotomized patients, as compared to the other two groups, the labeling index was significantly enhanced in the innervated antral mucosa where atrophic gastritis developed, but there was no change in the labeling index and no worsening of mucosal inflammation in the denervated fundic mucosa. The only abnormality in the latter was a striking expansion, towards the surface, of the proliferative area within the fundic pit. The labeling indices and the degree of gastritis in gastric mucosae are significantly correlated in control and duodenal ulcer patients. After superselective vagotomy, this correlation still existed in antral mucosa (r = 0.88, P less than 0.001) but not in fundic mucosa. If findings in antral mucosa, after superselective vagotomy, seemed related to gastritis lesions, those in fundic mucosa were not and may indicate an alteration due to the vagotomy per se.

Adolescent↗

Endocrine cell populations in the colon and rectum of cat, dog, and monkey: fine structure, immunocytochemistry, and distribution.

Comparative and quantitative ultrastructural studies of endocrine cells from the large bowel of European cat, beagle dog, and the monkey Callitrix jacchus were performed. The cat and monkey exhibited a roughly similar distribution of colonic endocrine cells with a frequency increasing toward the distal. On the contrary, the highest endocrine cell frequency in the dog colon was in the cecum. In the dog and monkey, enterochromaffin (EC) cells were predominant in all segments. In the cat, non-EC cells were predominant in the proximal colon. For each colonic segment, relative percentages of EC and non-EC cells appeared on the whole to be roughly stable between individuals of the same species. Three subtypes of EC cells were distinguished in each species. Non-EC cells were characterized by large variation in size and electron densities of their granules: Mean granule size per cell extended from 210 to 850 nm in cat, 310 to 770 nm in dog, and 130 to 470 nm in monkey. In each species, statistical analyses indicated that the non-EC cell population was composed of two or more subpopulations. Some similarities were found between colonic endocrine cells of the monkey and man, whereas obvious differences appeared between the two carnivorous mammals. Immunocytochemical studies demonstrated the presence of cells containing enteroglucagon, somatostatin, or a pancreatic polypeptidelike substance in the colon of the monkey and the rectum of the three mammals. Correlative immunocytochemical and ultrastructural studies showed that the three kinds of immunostained endocrine non-EC cells in each species had rather round granules, with great electron densities. Some subpopulations, morphologically distinguished, did not react to any of the antisera used. This suggests either the existence of secretory cycle in some endocrine cells or, perhaps, the presence of peptides still unknown in this part of the gut.

Animals↗

Trophic effect of some regulatory peptides on gastric exocrine and endocrine cells of the rat.

The effects of somatostatin and bombesin on gastric cells of the rat were demonstrated by measurement of epithelial cell proliferation after injection of tritiated thymidine and by quantification of cell populations. An 8 h-infusion of somatostatin transiently reduced labelling and mitotic indices in fundic and antral mucosae of normal rats and inhibited the growth stimulating effect of gastrin for a longer period of time. Three weeks administration of long-acting somatostatin preparation in combination with gastrin to normal rats, or alone to rats with chronic endogenous hypergastrinaemia, significantly antagonized the trophic effect of gastrin on the parietal cell population. An 8 day administration of bombesin by subcutaneous injection significantly increased the labelling index of antral gastrin cells compared to controls but did not change the labelling index of antral somatostatin cells. Quantification of the total antral gastrin cell population in bombesin-treated rats demonstrated a significant gastrin cell hyperplasia, which was correlated to the increase in gastrin content found in antral tissue. We conclude that cell kinetic and morphometric methods are complementary tools for the study of in vivo trophic effects of hormones.

Animals↗

[Gastric secretory, ultrastructural and pH changes during prolonged treatment with omeprazole in a severe form of Zollinger-Ellison syndrome].

Omeprazole, a powerful and long-lasting gastric anti-secretory benziimidazole derivative has been used to treat a particularly severe case of Zollinger-Ellison syndrome with familial type I multiple endocrine involvement. Before treatment with omeprazole, the patient's basal acid secretion, ranging from 50 to 100 mmol/h, had been poorly controlled by cimetidine (doses of up to 2,400 mg/d), ranitidine (doses of up to 1,200 mg/d) and even by ranitidine (1,200 mg/d) combined with pirenzepine (150 mg/d). Upon oral administration of four 20-mg capsules of omeprazole twice daily, rapid healing of the diffuse mucosal ulcerations of the upper GI tract as well as control of diarrhea were achieved. Clinical benefit accompagnied dramatic and sustained reductions in gastric acid secretion as demonstrated by repeated basal output measurements and 24-hour intragastric pH recording. The biodisponibility of omeprazole improved as gastric intraluminal acidity was reduced. The effects of omeprazole on pepsin output appeared to be mainly related to the reduction of gastric secretory volume. After more than one year of treatment, neither clinical nor biological side-effects were noted. However, repeated ultrastructural studies of fundic gastric mucosa revealed two types of alterations: a) a pattern of hyper-stimulated parietal cells with turgescent intra-cellular micro-canalicus invested by numerous microvilli; b) in about a fourth of the parietal cells, cytoplasmic modifications resembling auto-phagosomia and mitochondrial reduction in number and morphological transformation. Poorly understood to date, these alterations call for regular histological control of the gastric mucosa in patients with Zollinger-Ellison syndrome submitted to long-term administration of large doses of omeprazole.

Adult↗

[Influence of rectal preparation by enema on cell proliferation in the normal rectal mucosa in man].

In order to study the potential influence of rectal enemas on epithelial cell proliferation, two groups of 13 patients without any disease of the digestive tract were compared, one group having received two warm enemas (Normacol) prior to proctoscopic examination. Cell proliferation was studied by in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautographic analysis of the number and position of labeled nuclei in the glands. The mean number of labeled cells per gland and the mean labeling index were significantly higher in group i (with enemas) than in group II (without enema). In group I there was an extension of the proliferative compartment towards the surface with less than 50 p. 100 of labeled cells located in the lower third of glands. Intraindividual variations of labeling index from gland to gland were more important in group I than in group II. In group I, eight out of 13 patients had rectal glands with elevated labeling indices (15 p. 100) in contrast to one patient in group II. Our results suggest that proliferation abnormalities observed in group I are related to enema administration and indicate that this type of rectal preparation should preferably be excluded whenever cell kinetic parameters are studied in the rectal mucosa.

Adult↗

Epithelial cell proliferation in the rectal stump of patients with ileorectal anastomosis for ulcerative colitis.

Epithelial cell proliferation in the rectal stump after ileorectal anastomosis for ulcerative colitis was studied in 19 patients. This was achieved through in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautographic analysis of the number and position of labelled nuclei in the crypts. Rectal biopsies from nine unoperated patients with ulcerative colitis and from 10 controls, were processed simultaneously. Except for one, all patients were clinically in remission. The crypt length and number of labelled cells per crypt column were found to be similar in the rectal mucosa from the three groups of subjects. The mean labelling index, although low 8.9%, was higher (p less than 0.05) in operated patients compared with controls; but the dispersion of individual values was similar in both groups. There was an extension of the proliferative compartment towards the surface in 88% of unoperated patients and in 60% of operated patients. In addition, there was a shift of the major zone of proliferation from the lower to the middle third of the crypt in 17% of operated patients and from the lower to the upper third of the crypt in 14% of unoperated patients. No correlation was found between the labelling index and either the age of patient, the duration of disease or the period elapsed after ileorectal anastomosis. Interestingly, among operated patients with a colitis for over 10 years, 42% had a quite normal proliferative pattern with a corresponding mean postoperative period of 7.5 years.

Adolescent↗

Chronic administration of bombesin stimulates antral gastrin cell proliferation in the rat.

Bombesin tetradecapeptide, administered in gelatin twice daily for 1 wk, significantly increased the antral gastrin content in rats by stimulating antral gastrin cell proliferation. The labeling index of gastrin cells after five daily injections of [3H]thymidine given during bombesin treatment was significantly enhanced as compared with controls, while no modification in the pattern of antral somatostatin cell labeling was revealed. Total antral gastrin cell population at the end of bombesin treatment also increased significantly. Morphometric measurements at the electron microscope level showed that the mean size of gastrin cell in the bombesin-treated group was the same as in the control group. The size of gastrin secretory granules and their number per cell did not change. The present findings demonstrate that chronic administration of bombesin induces gastrin cell hyperplasia in the rat.

Animals↗

Self-replication of somatostatin cells in the antral mucosa of rodents.

The possibility that antral somatostatin cells have a self-replicating activity has been studied in three species of rodents: mice, rats and guinea-pigs, after a flash tritiated thymidine injection. The immunocytochemical staining of somatostatin cells, using specific antiserum, was combined with radioautographic procedures. The labelling index for somatostatin cells--and for gastrin cells identified on serial sections--was established after counting a large number of cells at the optical microscope level, on parallel tissue strips removed throughout the entire antrum. A significant percentage of the somatostatin cell population synthesized DNA. Values were similar for the three species of rodents ranging from 0.8 to 1.1%, that is slightly higher than the percentage of labelled gastrin cells, which was 0.67-0.7%. After a 36-hr continuous infusion of radioactive precursor in one rat, the labelling index observed remained low; 2.33% for somatostatin cells and 1.68% for gastrin cells. Colchicine injection in mice allowed the observation of mitotic figures in well differentiated somatostatin cells. Four hours after that injection, the mitotic index was estimated roughly at 0.3%. Thus, evidence has been presented that in rodents a fraction of the antral somatostatin cell population is capable of dividing, similar to the situation in gastrin cells.

Animals↗

Streptozotocin treatment in pancreatic cholera (Verner-Morrison) syndrome.

A case of pancreatic cholera (Verner-Morrison syndrome) associated with a pancreatic endocrine tumor and hepatic metastases is presented. VIP and HPP plasma levels, initially elevated, were accurately followed in various conditions: during corticosteroid therapy, after pancreatic tumor excision, during and after streptozotocin therapy (1.5 g/m2) by repeated intraarterial route). Only streptozotocin therapy resulted in a reduction of the stool volume with concomitant decrease in VIP plasma levels. However, the size of the hepatic metastases was unchanged and HPP plasma levels remained elevated. It is suggested that VIP represents the tumoral secretion and HPP a marker of the residual malignant tissue.

Adenoma, Islet Cell↗

Inhibitory effect of prolonged administration of long-acting somatostatin on gastrin-stimulated fundic epithelial cell growth in the rat.

The effects of a 3-week administration of long-acting somatostatin were explored (a) in young rats under both normal and long-acting gastrin stimulation and (b) in adult rats with transposition of the antrum onto the colon and, therefore, chronically stimulated with endogenous gastrin. Histomorphometric parameters of the fundic mucosa were estimated at the end of the treatment. In young rats, somatostatin alone (390 micrograms/kg/day) only lowered parietal and peptic cell densities per cubic millimeter compared to controls. That it exerted an antitropic effect under physiological conditions remains questionable. However, in cases of chronic hypergastrinemia, the same dose of somatostatin obviously antagonized the growth-promoting effect of exogenous or endogenous gastrin.

Animals↗

Correlative immunocytochemical and electron microscopic studies: identification of (entero)glucagon- somatostatin- and pancreatic polypeptide-like-containing cells in the human colon.

Correlative immunocytochemical and electron microscopic studies, using the semi thin-thin technic, were performed to identify the (entero) glucagon, somatostatin and pancreatic polypeptide-like immunoreactive cells of the human colonic mucosa. Mean granule diameter for each cell type was estimated according to two methods and histograms showing the granule size distribution were constructed. A total of 139 immunostained cells identified at the ultrastructural level were analyzed. Mean granule diameter for (entero)glucagon-containing cells was 318 +/- 11 nm but a reduction of granule size with age was noteworthy: granules were larger in the fetus (mean diameter 350 +/- 15) than in adults (mean diameter 310 +/- 10 nm). Somatostatin-containing cells, very rare in adults, were present in the fetal distal colon. Their general mean granule diameter was 354 +/- 18 nm but many cells had a mean granule diameter of more than 400 nm. A pancreatic polypeptide-like immunoreactivity was found only in (entero)glucagon-containing cells, pointing out the possible occurrence of both peptides (or of similar sequences) in the same cells. Previous ultrastructural studies dealing with a tentative classification of the human colonic endocrine cells were compared with the present data.

Adult↗

Emiocytotic granule release without intraluminal stimulus in human colonic endocrine cells of fetuses, children and adults.

In endocrine cells of the colon of adults, children and fetuses, exocytotic granule release without any specific stimulation is reported. Omega-invaginations are observed on both the lateral and basal surfaces of all types of colonic endocrine cells. Several explanations for the phenomenon are suggested: 1) emiocytosis is probably more frequent in the colon than in the proximal gut, this allows its observation without requiring an exogenous stimulus, 2) since most of the exocytotic figures are from anaesthetized subjects it is also assumed that contraction of the muscular layer induced by anaesthetics and the resulting increase in intraluminal pressure were the possible causes of granule release, 3) in non-anaesthetized subjects release may have taken place in response to a normal endogenous physiological stimulus, or to the dilation of colon during colonoscopy. Certain figures on lateral surfaces between endocrine and adjacent cells i.e., bulges of parallel plasma membranes surrounding a secretory granule, were observed. Their significance is unknown.

Adult↗

Quantitation of gastrin and somatostatin cell populations in the antral mucosa of the rat. Comparative distribution and evolution through different life stages.

Total antral gastrin and somatostatin cell populations as well as their relative distribution pattern throughout the antrum were studied in rats with advancing age from birth time to old age. Both endocrine cell populations were estimated, after staining by immunoperoxidase technique, with a quantitative method using serial parallel strips from entire stomachs. Gastrin cells were regularly found at less than 1 h of post-natal life, but were few in number (447 +/- 82) cells. Somatostatin cells, not seen at birth, were observed in all rats at seven post-natal days; then they increased in number less rapidly but more regularly than gastrin cells. During the normal adult period, corrected gastrin cell population corresponds to about 330,000-500,000 cells and corrected somatostatin cell populations to about 130,000-200,000 cells. For the whole antrum the ratio of gastrin cell to somatostatin cell populations decreases through the rat life from 6.5 at 7 days to 1.5 in old age with a stable value, 2.5, during adult period. Examination of the topographical distribution throughout the antrum of these two populations shows that, strip per strip, their numerical ratio varies. Homogeneous values for the latter occur in the middle part of antrum and, as rule, in each group they reflect the mean value calculated for the whole of the antrum.

Aging↗

Ontogeny and distribution of certain oendocrine cells in the human fetal large intestine. Histochemical and immunocytochemical studies.

In 9 fetuses, 9 to 24 weeks-old, the occurrence and relative distribution of argentaffin cells, as well as of cells immunoreactive to somatostatin (SRIF), glucagon-like polypeptide (GLI), pancreatic polypeptide (PP) and substance P (SP) were studied in five segments of the colon (appendix, cecum, ascending colon, descending colon, and rectosigmoid). For each colonic segment, data concerned with the occurrence of endocrine cells were expressed either as mean absolute numbers of specific cells per entire mucosal section, or as cell densities per mm3 of mucosa after calculation of the mucosal volume of the sections. Argentaffin, GLI, SRIF and PP immunoreactive cells are all present in relatively large numbers, scattered along the entire length of the colonic mucosa as early as the 9th-10th week of gestation, whereas substance P-containing cells occur sporadically and first appear during the 4th-17th week. Until the 20th week, with progressing embryonic development, an increase was determined in absolute numbers per section of all types of endocrine cells in all segments of the colon. This observation is clearly related to the general growth of the colonic mucosa, since cell densities per mm3 of mucosa do not greatly change or even decrease during gestation. However, it is possible that densities of argentaffin, GLI and BPP cells increase in the appendix around the 14th-17th week of gestation. Between 20th and 24th weeks, absolute numbers of cells per section remain stable or slightly increase, while cell densities tend rather to decrease in all segments. These data demonstrate that some endocrine cells are present very early in the human fetal colon, but their functional significance remains to be elucidated.

Colon↗

Effect of somatostatin on normal and gastric-stimulated cell proliferation in the gastric and intestinal mucosae of the rat.

The effects of an 8-hour infusion of somatostatin, saline, gastrin or a mixture of gastrin + somatostatin on DNA synthesis and mitotic activity of gastrointestinal progenitor cells were explored in conscious rats, using in vivo labeling with 3H-thymidine and radioautography. Infusion of somatostatin (day or night) was shown to transiently reduce nuclear uptake of 3H-thymidine and cell division in both fundic and antral progenitor cells. Cell DNA synthesis in the gastrin + somatostatin-stimulated stomach was lower than in the gastrin-stimulated stomach. In the intestine, nocturnal infusion of somatostatin decrease DNA synthesis whereas diurnal infusion decreased cell division but no effect was observed on gastrin stimulation. Evidently, somatostatin may inhibit, perhaps indirectly, the cell proliferation in digestive mucosae and antagonize the trophic activity of gastrin but only in fundic and antral mucosae.

Animals↗

Endocrine cells of the colon in Hirschsprung's and control children.

The large intestine resected from 6 Hirschsprung's patients and surgical colonic biopsies from 6 control children were examined with light and electron microscopy. The presence and the relative distribution of various endocrine cell types in both groups of mucosa were determined. In light microscope studies endocrine cell data were expressed as number of cells per unit area of mucosa using a quantitative method after argentaffin and Grimelius's argyrophilic techniques and an immunoperoxidase reaction with glucagon and somatostatin (SRIF) antisera. The results indicate that endocrine cells are apparently not involved in Hirschsprung's disease, since their number and frequency did not differ significantly between the ganglionic and aganglionic segments of Hirschsprung's patients nor between the latter and control children. Glucagon immunoreactive cells were, on the average, 5-6 times and 7-9 times more numerous that SRIF cells in the rectum and the sigmoid, respectively. Ultrastructurally, five endocrine cell types could be distinguished. The fifth type, probably a transition type, apparently disappears in adults.

Child, Preschool↗