[Epigastric symptoms and alcohol drinking in a mechanic].
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Abdominal Pain↗
Biomedical subjects
R Eissele
Publications and source records attributed to R Eissele.
[Gastrointestinal problems in the elderly. The stomach].
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Aged↗
Expression, intracellular localization, and gene transcription regulation of the secretory protein 7B2 in endocrine pancreatic cell lines and human insulinomas.
7B2 is a 23-kDa protein encoded by a single gene that is expressed in a variety of neuroendocrine tissues. Although its physiological role has not yet been elucidated, its presence in secretory granules suggests a function in the secretory machinery of certain neuronal and endocrine cells in various species. The present study characterizes the expression of 7B2 in endocrine pancreatic cells. We demonstrate that: (i) 7B2 is highly expressed in human insulinomas; (ii) its ultrastructural localization, associated with secretory granules of A and B cells of the islets, suggests a participation of 7B2 in the secretion of insulin and glucagon; (iii) sequences located in the first intron of the 7B2 gene are required for its transcription in either insulinoma or glucagonoma cell lines; and (iv) in a B cell-like insulinoma cell line, the transcription of 7B2 is regulated by protein kinase A and protein kinase C activators, while in an A-like insulinoma cell line, 7B2 gene transcription seems to be constitutively activated.
Animals↗
Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study.
The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas.
The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Rat gastric somatostatin and gastrin release: interactions of exendin-4 and truncated glucagon-like peptide-1 (GLP-1) amide.
The effect of exendin-4, a peptide of the secretin-glucagon family with high homology of amino acid sequence with glucagon-like peptide-1 (GLP-1), on gastric hormone release was investigated in the isolated perfused rat stomach. Exendin-4 dose dependently stimulated somatostatin release up to 9-fold at a concentration of 10(-7) M whereas gastrin release was inversely inhibited by up to 63%. These effects could partially be reduced by concomitant perfusion of truncated exendin-4, exendin(9-39)amide. Similarly, stimulation of somatostatin secretion and inhibition of gastrin release induced by GLP-1(7-36)amide was partially reversed by exendin-4 (9-39)amide. These data are consistent with the assumption that exendin-4 and truncated GLP-1amide exert their effects on gastric D and G cell by interaction with the same receptor.
Animals↗
Sodium butyrate induces neuroendocrine cytodifferentiation in the insulinoma cell line RINm5F.
The differentiating agent sodium butyrate inhibits proliferation and stimulates cell-specific hormone expression in rat insulinoma cells. In this study, we investigated the effect of sodium butyrate on neuroendocrine cytodifferentiation in the rat insulinoma subclone, RINm5F. The cells were cultured with 0.5, 1, or 1.5 mM sodium butyrate for up to 72 h. Ultrastructurally, cells cultured with 1 mM sodium butyrate revealed a more differentiated appearance with an induction of cellular compartments involved in regulated insulin secretion. Morphometric analysis showed a significant elevation of neuroendocrine granule density. The total area of the specific granules was increased after incubation with 1 mM sodium butyrate for 48 and 72 h. Proliferation of RINm5F cells was inhibited by sodium butyrate in a dose-dependent manner. DNA production ceased completely within 24 h at 1.5 mM sodium butyrate. This concentration of sodium butyrate increased the cellular insulin content 8.9-fold and the insulin production 2-fold after 72 h. The insulin release was reduced from 79 +/- 3.5% in controls to 37 +/- 5.6% of total in a 24-h incubation period after 3 days of culture with 1.5 mM sodium butyrate. Insulin mRNA levels increased to a maximum of 324% compared with controls after 48 h of culture with 1.5 mM sodium butyrate. Chromogranin A mRNA levels increased to a similar extent (368 +/- 26%), whereas sodium butyrate did not stimulate the expression of synaptophysin, a major membrane component of small neuroendocrine vesicles. In conclusion, our data suggest the selective induction of neuroendocrine cytodifferentiation by sodium butyrate in RINm5F cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Blotting, Northern↗
Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment.
The gastric proton pump H+/K(+)-ATPase in the parietal cell is central to acid secretion into the stomach. We performed the following experiment to examine the pattern of expression of the alpha- and beta-subunits of the H+/K(+)-ATPase at the transcriptional level during 7 days' application of the proton pump inhibitor omeprazole, in relation to the expression of gastrin and histamine, two stimuli of gastric acid secretion. Serum gastrin concentrations and mRNA levels of antral gastrin, fundic histidine decarboxylase (HDC) and H+/K(+)-ATPase alpha- and beta-subunits were determined after 8 h, 1, 3 and 7 days. Omeprazole treatment rapidly caused an increase in the serum gastrin concentration and the antral gastrin mRNA level after 3 days. HDC mRNA expression showed a steady increase with a 5-fold induction after 1 week. However, mRNA levels of the alpha- and beta-subunits of the H+/K(+)-ATPase were unchanged during the course of omeprazole treatment. These results suggest that omeprazole inhibition of the gastric proton pump does not result in feedback activation of H+/K(+)-ATPase gene expression despite adaptive changes of the endocrine stomach.
Animals↗
[Risk for developing tumors in therapy with the proton pump inhibitor omeprazole].
The experience received hitherto with the treatment of omeprazole proves this drug as absolutely save and poor of side effects. ECL-cell hyperplasia and carcinoids which occur during application of very high doses of omeprazole in rats are not caused by a direct effect of omeprazole. These changes are induced by extremely elevated serum gastrin levels due to achlorhydria. However, these high doses of omeprazole are not applicated in man. Therefore, the results from animal studies can not be applied on humans. During long-term treatment with omeprazole in most patients only slight increases of serum gastrin levels and ECL-cell densities occur. Only a very few patients exhibit a progressive and marked increase of serum gastrin levels. These patients should be carefully monitored by endoscopy in regularly intervals. There is no current evidence to support the contention that omeprazole is genotoxic. Results from Burlinson on the potential of omeprazole to induce DNA damage proved to be unsounded and of no clinical relevance. Omeprazole produced negative results in all well established genotoxicity tests. The incidence of neoplasias in the stomach is not increased after long-term acid suppression as indicated by 15 years application of H2-blockers and even a longer period of experience with vagotomy. Hitherto, there is also no evidence that acid inhibition induced by omeprazole causes an increased rate of carcinoma of the stomach. The risk for promoting carcinomas of the colon by the mild hypergastrinaemia during treatment with omeprazole seems to be inferior. In addition the correlation between development of carcinomas of the colon respective rectum and hypergastrinaemia is discussed controversly.
Animals↗
Gastric argyrophil (enterochromaffin-like), gastrin, and somatostatin cells after proximal selective vagotomy in man.
The number, size, and volume density of endocrine cells was determined in biopsies obtained endoscopically in patients after proximal selective vagotomy (PSV; N = 31), antrectomy (N = 9), untreated duodenal ulcer (DU) disease (N = 11), and in controls (N = 15). Serum gastrin was significantly elevated after PSV (mean 60 pg/ml) compared to DU patients (29 pg/ml), controls (26 pg/ml), and after antrectomy (11 pg/ml). Volume density of fundic argyrophil (largely enterochromaffin-like) cells after PSV (0.74%) and in DU disease (0.63%) were significantly (P < 0.001) higher when compared with controls (0.37%) but lower after antrectomy (0.24%; P < 0.02). The density of argyrophil cells was not influenced by the interval following PSV or the magnitude of hypergastrinemia. Antral gastrin cells were increased after vagotomy, whereas the antral and fundic somatostatin cell numbers were reduced after PSV. It is concluded that: (1) a major role of the vagal nerve as a trophic factor for enterochromaffin-like cells could not be demonstrated after PSV, and (2) moderate hypergastrinemia after PSV did not induce proliferation of ECL cells.
Adult↗
The long-term prognosis of AA and AL renal amyloidosis and the pathogenesis of chronic renal failure in renal amyloidosis.
Investigation of the long-term prognosis and pathogenesis of chronic renal failure in 225 cases of AA and AL renal amyloidosis (perireticular and perireticular + pericollagenous amyloidosis) yielded the following results: 1) The prognosis of both AA and AL amyloidosis is poor, and is worse than all other types of glomerulopathy with the exception of rapidly progressive glomerulonephritis. 2) The probability of maintaining renal function in AL amyloidosis is no lower than that in AA amyloidosis. 3) The prognosis of both AA and AL amyloidosis is significantly worse in cases in which the renal cortical interstitium exhibits fibrosis at the time of the biopsy than in those in which it is normal. 4) In AA and AL amyloidosis, as in various types of inflammatory glomerulopathy, the relative area of the renal cortical interstitium shows a significant positive correlation with the serum creatinine concentration and a significant negative correlation with the creatinine clearance. However, the extent of interstitial amyloid deposition does not correlate with the serum creatinine concentration. Deposition of amyloid in the renal cortical interstitium has no effect on renal excretory function. 5) The long-term prognosis of renal amyloidosis is related to the severity of the glomerular amyloidosis in as much as it is generally worse in Grades III to V than in Grades I and II. However, it must be borne in mind that the incidence of interstitial fibrosis, which is decisive for the long-term prognosis, increases with the severity of glomerular changes. 6) The long-term prognosis of renal amyloidosis is worse if acute renal failure or interstitial fibrosis is present at the time of the biopsy. Patients with both acute renal failure and interstitial fibrosis have the worst prognosis. 7) Isolated glomerular amyloidosis, even if there is severe vascular amyloidosis (vas afferns), does not lead to renal insufficiency or even to a rise in serum creatinine concentration. 8) The number of T lymphocytes in the tubular epithelium in AA and AL amyloidosis is significantly greater than normal, and the number of T lymphocytes, macrophages/monocytes, and fibroblasts/fibrocytes per unit area of interstitium is also significantly increased. 9) As far as the pathogenesis of renal cortical interstitial fibrosis in renal amyloidosis is concerned, it is proposed that, in some cases, this develops from the interstitial edema that is seen in biopsy specimens of patients with renal amyloidosis and acute renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Immunoreactivity and expression of amylin in gastroenteropancreatic endocrine tumors.
Amylin was isolated from human insulinomas, but there has been only preliminary data regarding whether this peptide can also be detected in other types of gastroenteropancreatic endocrine tumors. In the present study, immunohistochemical staining of 87 gastroenteropancreatic endocrine tumors demonstrated amylin immunoreactivity in 21.8% of the neoplasmas. Thirteen of 15 insulinomas, three of 21 gastrinomas, two of 29 nonfunctioning tumors, and one of 18 carcinoids were amylin-immunoreactive. Seventeen of the 19 amylin-immunoreactive tumors were primarily located in the pancreas, but two tumors were found in the intestine. Measurements of amylin messenger RNA expression in a few tumors revealed amylin synthesis in these tumors. Amylin immunoreactivity did not correlate with invasion and metastasis. However, the rate of curative resections was significantly higher in amylin-immunoreactive tumors. These results demonstrate for the first time that amylin immunoreactivity is not restricted to insulinomas and can also occur rarely in endocrine tumors of the intestine.
Amyloid↗
Effect of gastrin receptor blockade on endocrine cells in rats during achlorhydria.
Hyperplasia of the oxyntic enterochromaffinlike cells in response to long-lasting blockade of acid secretion is closely related to hypergastrinemia. In the present study, the effect of a specific gastrin receptor antagonist on proton pump inhibitor-induced changes on serum gastrin levels, mucosal height, as well as gastrin- and enterochromaffin-like cells was investigated in rats. The proton pump inhibitor BY 308 or the vehicle methylcellulose [Methocel (controls)] was administered for 2 weeks in the presence and absence of the gastrin receptor antagonist PD 136450 (CAM 1189). BY 308 significantly increased serum gastrin levels, gastrin cell density, and antral gastrin concentration. Concomitant application of PD 136450 did not alter this response. In the oxyntic stomach, mucosal height, enterochromaffinlike cell density, labeling index of enterochromaffinlike cells, and histamine concentration were elevated after treatment with BY 308. These increases were almost completely abolished by PD 136450. Even in normogastrinemic control rats, PD 136450 significantly decreased mucosal height of the oxyntic part of the stomach and the labeling index of enterochromaffinlike cells. The results show that (a) trophic effects of drug-induced achlorhydria are mediated by gastrin; (b) even in control rats (normogastrinemic), gastrin is a trophic factor for the oxyntic mucosa; and (c) antral gastrin cell hyperplasia in states of chronic achlorhydria is not mediated by gastrin itself.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man.
A highly specific monoclonal antibody directed against the C-terminal part of glucagon-like peptide-1 (GLP-1) was raised to immunohistochemically evaluate the distribution of GLP-1 containing cells in the entire gastrointestinal tract including pancreas of rat, pig and man. In the pancreas GLP-1-immunoreactive cells were found variously shaped and predominantly located in the periphery of the islets. Ultrastructurally, GLP-1 was co-localized with glucagon in the alpha-granula of A-cells and was mainly restricted to the electrondense core. In the intestine open type cells reaching the lumen via a slender apical process were stained with the GLP-1 antibody. They occurred in all parts of the crypts but predominantly in the basal portion. The density of GLP-1 immunoreactive cells varied between species in a characteristic order: rat greater than pig greater than man. In pig and human gut a large number of cells occurred in the distal jejunum and ileum. A continuous increase of cell densities was found from the proximal to the distal colon resulting in highest numbers in the rectum. In rats the highest cell density occurred in the ileum. Again, a continuous increase of GLP-1-positive cell numbers was evident from the proximal to the distal portion of small and large bowel. GLP-1 was partly co-localized with PYY. The GLP-1 positive cells appeared electronmicroscopically as L-cells with the typical large granula. This morphological data indicates that GLP-1-releasing cells in the small intestine are appropriately positioned in the distal part to sense and respond to the presence of nutrients that have escaped the absorptive surface of the upper small intestine.
Animals↗
Effect of gastrin receptor antagonists on gastric acid secretion and gastrin and somatostatin release in the rat stomach.
The effects of two recently developed gastrin receptor antagonists, PD 136450 and L-365,260, on pentagastrin-stimulated acid secretion were investigated in rats. PD 136450 at a dose of 6 mg/kg s.c. (9.6 mumol) completely abolished acid secretion induced by pentagastrin. The inhibition of 18 mg/kg PD 136450 s.c. lasted for at least 8 h and was still effective after 14 days of treatment (18 mg/kg s.c. every 8 h). Acute application of L-365,260 at a dose of 3.8 mg/kg, which is equimolar (9.6 mumol) to 6 mg/kg PD 136450 reduced acid responses slightly. However, when L-365,260 was administered intravenously at a dose of 3 mg/kg, this antagonist completely abolished the pentagastrin-stimulated acid secretion. Furthermore, the effect of PD 136450 on endogenous gastric somatostatin and gastrin releases was tested in the isolated, vascularly perfused rat stomach. PD 136450 perfused at a concentration of 1 microM slightly increased somatostatin secretion after stimulation with a high dose of isoproterenol (10(-7) M). There was no effect of PD 136450 on basal or acetylcholine-stimulated gastrin secretion.
Animals↗
Adaptation and renewal of the endocrine stomach.
At present at least seven different endocrine cell types have been identified in the stomach. According to their relative frequency and secretion products the antral gastrin producing G cell and somatostatin producing D cell and the fundic histamine producing ECL cell are the best characterized cell types. Total endocrine cell mass is controlled by various factors from inside and outside the stomach. Density of antral G and D cells depends on the presence and absence of food, on the antral pH and on additional humoral and/or neural factors. Gastrin and not gastric pH has been identified as the most important factor regulating the density of fundic ECL cells. Adaptation of gastric endocrine cells to gastric pH and to the presence, abundance or absence of humoral and neural regulators are well known phenomena though only partially understood. Antral G cells increase and antral D cells decrease during long-term achlorhydria which as a consequence leads to hypergastrinaemia. Examples are pernicious anaemia in man and drug-induced acid suppression under experimental conditions. Interestingly, achlorhydria-induced G cell hyperplasia never progresses to gastrinomas. Fundic ECL cell density increases markedly in the presence of long-lasting hypergastrinaemia independently of gastric pH. In contrast to G cells ECL cell hyperplasia may progress to rarely occurring ECLomas. However, this depends on additional conditioning factors as the presence of severe atrophic gastritis as in pernicious anaemia or a specific genetic trait present in patients with gastrinomas associated with the MEN I syndrome.
Adaptation, Physiological↗
[Importance of glomerular and tubulointerstitial changes for long-term prognosis of AA- and AL-amyloidosis. An analysis of 225 cases].
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Adult↗
Role of cholecystokinin in the control of gastric somatostatin in the rat: in vivo and in vitro studies.
Cholecystokinin (CCK) has been shown to be a powerful stimulus for somatostatin release from isolated canine fundic D-cells in short-term culture. The influence of the CCK analogue caerulein on the secretory activity of the D-cell in the intact stomach in vitro and the effect of elevated plasma levels of endogenous CCK on gastric somatostatin stores in vivo were investigated in the rat. Basal somatostatin secretion from the isolated, vascularly perfused rat stomach preparation was not affected by various doses of caerulein. Slight stimulation of somatostatin-like immunoreactivity (SLI) release by epinephrine was significantly inhibited by caerulein, whereas caerulein did not alter half-maximal stimulation of SLI secretion by isoproterenol. Rats with chronically elevated plasma CCK levels induced by experimental exocrine pancreatic insufficiency did not show any change in tissue concentrations of SLI or in D-cell number, both in the antrum and corpus. These data suggest that CCK--in contrast to dogs--is not an important modulator of gastric somatostatin in the rat.
Animals↗