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Biomedical subjects

G E Feurle

Publications and source records attributed to G E Feurle.

At least 37 records · Page 2Linked to original sources
PubMed1995

The role of CCK and its analogues in the organogenesis of the fetal rat pancreas.

The gastrointestinal peptide cholecystokinin (CCK) has been shown to stimulate pancreatic growth in the adolescent and adult rat. However, little is known about the role of gastrointestinal hormones in the regulation of organ formation during fetal development. We therefore examined the effects of the CCK receptor antagonist devazepide (25 micrograms/h) and an antigastrin/CCK monoclonal immunoglobulin G on the maternal and fetal rat pancreas. These substances were infused subcutaneously with minipumps in female rats during the entire period of gestation. At the end of gestation, the rats were killed and the pancreata of the dams and their litter were examined for DNA and protein. In the dams, the receptor antagonist and the antibody against CCK/gastrin had no effect. In the newborns, the CCK receptor antagonist led to a significant reduction of the protein and DNA concentration [protein in controls, 105.0 +/- 3.75 micrograms/mg pancreatic tissue; in the antagonist group, 91.9 +/- 4.2 micrograms/mg pancreatic tissue (p < 0.05); DNA in controls, 1.28 +/- 0.19 micrograms/mg pancreatic tissue; in the antagonist group, 0.48 +/- 0.06 micrograms/mg pancreatic tissue (p < 0.05) (mean +/- SEM)]. Immune neutralization of CCK/gastrin in the maternal-fetal circulation induced a reduction of the protein concentration in the fetal pancreas (85.3 +/- 3.06 micrograms/mg pancreatic tissue; p < 0.01) but had no effect on fetal pancreatic DNA. Additional experiments indicated effective concentrations of the CCK receptor antagonist in fetal pancreatic tissue and free binding sites of the circulating antibody. In conclusion, the study provides evidence that CCK and its analogues are involved in fetal pancreatic organogenesis.

Animals↗
PubMed1994

Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple's disease.

Several small studies have indicated an impaired cell mediated immune response as a possible cause for the delayed elimination of the bacteria in Whipple's disease. A specific defect, however, has not been defined. We examined the expression of cell surface molecules and mitogenic responses of peripheral blood mononuclear cells in 27 patients with Whipple's disease at different disease stages by indirect immunofluorescence and by measurement of [3H]thymidine incorporation, respectively. E-rosette formation and cutaneous reaction to seven recall antigens were determined. Matched healthy donors served as controls. We found a significantly reduced number of cells expressing the complement receptor 3 alpha-chain (= CD11b) in all patients. In florid disease, the number of activated cells (in particular CD58 positive cells) was increased and CD4/CD8 ratios were diminished. Proliferation to phytohemagglutinin and to sheep red blood cells was reduced at all stages of the disease. Serum of control persons reversed this decreased responsiveness especially in patients with active disease. Skin reaction was hypoergic in all patients. Determination of CD58 positive cells increased in patients with active disease may be useful to define the activity of the disease and the duration necessary for treatment. Transient inhibiting serum activities may impair the CD2/CD58 interaction. The reduction of cells expressing CD11b, the decreased proliferation, and the cutaneous hypoergy indicate a persisting defect of cell mediated immunity in vivo and in vitro. These defects may contribute to the impaired ability of patients with Whipple's disease to eliminate bacteria.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1994

An evaluation of antimicrobial treatment for Whipple's Disease. Tetracycline versus trimethoprim-sulfamethoxazole.

Whipple's disease is a multisystemic disorder in which almost all organ systems can be invaded by rod-shaped bacteria. Without extended antimicrobial therapy, its course is lethal. Empirically, treatment consists of tetracyclines given for one to two years. Trimethoprim-sulfamethoxazole, a compound that crosses the blood-brain barrier, has been suggested as an alternative when patients were observed with progressive cerebral involvement. There has never been a formal evaluation of the selection of antibiotics for the treatment of Whipple's disease. In the present nonrandomized, partially retrospective study, we compared the result of two treatment regimens in 30 patients, all examined personally. Twenty-two patients were treated with tetracycline and eight patients with trimethoprim-sulfamethoxazole. In five patients, therapy with tetracycline was changed to another antimicrobial agent because of treatment failure or drug intolerance. The main treatment measure was disappearance of the clinical symptoms such as weight loss, arthritis, malabsorption, fever, edema, central nervous system manifestations, lymphadenopathy, and congestive heart failure. Drug intolerance requiring a change of medication was also considered a treatment failure. We found that trimethoprim-sulfamethoxazole induced complete clinical remission in 12 of 13 treatment cycles, tetracycline in 13 of 22 treatment cycles (P < 0.05; mean difference 33%; 95% confidence interval 8% to 58%). Trimethoprim-sulfamethoxazole was also more efficacious than tetracycline in the treatment of cerebral Whipple's disease. However, trimethoprim-sulfamethoxazole did not prevent cerebral manifestations in all cases. The only deaths due to Whipple's disease occurred in patients with cerebral involvement. It is concluded that treatment with trimethoprim-sulfamethoxazole was significantly superior to that with tetracycline in inducing clinical remission of Whipple's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Schedule↗
PubMed1994

Argyrophil cell hyperplasia and a carcinoid tumour in the stomach of a patient with sporadic Zollinger-Ellison syndrome.

In the rat, hypergastrinaemia induced by drug treatment with omeprazole or potent H2-receptor antagonists leads to the development of gastric enterochromaffin-like cell carcinoids. In man, gastric carcinoids induced by hypergastrinaemia have been described only in patients with chronic atrophic gastritis type A and in patients with the multiple endocrine neoplasia syndrome type 1. This patient with Zollinger-Ellison syndrome without gastric mucosal atrophy and without evidence of the multiple endocrine neoplasia syndrome developed an argyrophil gastric carcinoid tumour. This observation indicates that hypergastrinaemia in the sporadic Zollinger-Ellison-syndrome may induce gastric carcinoids.

Adult↗
PubMed1993

Effect of jejunal infusion of different caloric loads on pancreatic enzyme secretion and gastro-intestinal hormone response in man.

It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min-1 = 14.0 kJ min-1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min-1 (5.5 kJ min-1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3.3 kcal min-1 (14.0 kJ min-1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undefined inhibitor and a feedback mechanism is postulated.

Adult↗
PubMed1992

Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion.

One of the peptides previously discovered in amphibians is the octapeptide xenopsin. As immunohistochemistry has also indicated the presence of xenopsin immunoreactivity in man, we extracted in the present investigation xenopsin-immunoreactive material from human gastric mucosa and purified it to homogeneity with several high performance liquid chromatography (HPLC) reverse phase and ion exchange chromatographic steps. The eluates were monitored with a radioimmunoassay for amphibian xenopsin. Determination of the amino acid sequence revealed a 25-amino acid peptide having 6 C-terminal amino acids in common with amphibian xenopsin. The sequence of this peptide, termed xenin 25, is M-L-T-K-F-E-T-K-S-A-R-V-K-G-L-S-F-H-P-K-R-P-W-I-L. The peptide was custom-synthesized. Mass spectrometry of the synthetic and the extracted peptide revealed identical molecular mass. Purification of 250 ml of human postprandial plasma with Sep-Pak C18 cartridges, reverse phase HPLC, and ion exchange chromatography demonstrated circulating xenin immunoreactivity at a retention time identical to xenin 25. The amount of xenin immunoreactivity at the position of xenin 25 on C18-HPLC increased significantly after a meal. A radioimmunoassay utilizing antibodies to xenin 25 and a 125I-labeled analogue of xenin 25 was used to measure immunoreactive xenin in the plasma of 10 volunteers. There was a significant rise of xenin immunoreactivity in the plasma after a meal. Intravenous infusion of the synthetic peptide in dogs stimulated exocrine pancreatic secretion beginning at a dose of 4 pmol/kg/min. The maximal effect was seen with 64 pmol/kg/min. We have detected, therefore, a new peptide, xenin 25, in human gastric mucosa; we have provided evidence for the presence of this peptide in the human circulation, and have shown a rise of plasma xenin concentrations after a meal. This peptide stimulates exocrine pancreatic secretion. Its physiologic role deserves further investigation.

Amino Acid Sequence↗
PubMed1991

The site of action of neurotensin in the rat pancreas.

The tridecapeptide neurotensin, present in endocrine cells of the ileal mucosa and in nerve bodies of cerebral nuclei, may play a role in the physiology of exocrine pancreatic regulation. This assumption is based on two observations: Neurotensin appears in the blood stream after a fatty meal and neurotensin stimulates exocrine pancreatic secretion. There has, however, been controversy on the site of action of this peptide since some investigators did not observe an effect on the pancreas in vitro and suggested, therefore, an indirect, perhaps neural or even central site of action. In the present investigation, we compared the action of neurotensin on the exocrine pancreas in vivo in the anesthetized rat after intracerebroventricular (i.c.v.) injection and after i.v. infusion and in vitro after incubation of the pancreas in three different preparations: isolated dispersed acini, isolated lobuli, and isolated total pancreas. We found that i.c.v. application of neurotensin stimulated exocrine pancreatic secretion only when doses were applied that led to elevated peripheral plasma neurotensin levels. In vitro, the action of neurotensin was very weak and the optimal dose was integrity dependent; e.g., a concentration of 10(-4) and 10(-5) M neurotensin was necessary to stimulate amylase release from isolated acini, 10(-8) M neurotensin induced amylase release from isolates lobuli, and 10(-9) M neurotensin released amylase from the intact pancreas. Intravenously, neurotensin resulted in a greater amylase release over basal than in any of the in vitro experiments. We conclude that neurotensin acts directly on the pancreatic acini but that the sensitivity of the pancreas is greatly enhanced when the organ is intact and has normal neural and vascular communications.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1991

Acute small bowel ischemia without transmural infarction.

Two patients with atrial fibrillation had abrupt onset of abdominal pain and massive small bowel distension suggesting mesenterial artery embolism. One patient had dilation of the left atrium and ventricle, the other a mitral value prolapse syndrome with a dilated left atrium. Both patients were treated conservatively and gradually recovered. A small bowel series performed several weeks after the acute episode showed loss of normal mucosa and narrowing of a long segment of the small bowel. A control examination in one patient one year later, still revealed jejunal mucosal abnormalities and stenosis, features similar to those occurring in Crohn's disease. Our observations suggest that analogous to ischemic colitis, an entity of acute ischemic small bowel enteritis exists. Mesenteric ischemia apparently can induce a clinical syndrome of "regional enteritis". The radiologic features should not be confused with those of Crohn's disease.

Aged↗
PubMed1990

Distinct immunohistochemical findings in columnar epithelium of esophageal inlet patch and of Barrett's esophagus.

Immunohistochemistry was performed on biopsies of columnar mucosa from 11 patients with Barrett's esophagus and 11 patients with columnar mucosa in the cranial esophagus, the "inlet patch." Both epithelia contained endocrine cells, immunoreactive to antisera against serotonin, glucagon, somatostatin, and pancreatic polypeptide; the specialized mucosa of Barrett's esophagus contained, in addition, neurotensin-immunoreactive cells, and in the mucosa of an inlet patch we found a gastrin cell. These findings are not compatible with some of the current theories on the origin of these epithelia. The mucosa of the inlet patch has been considered to consist of heterotopic gastric mucosa. The mucosa of the adult human stomach, however, does not contain glucagon cells. These cells are only present in the early embryonic stomach, and they disappear during embryonogenesis. According to our findings, the mucosa of the inlet patch therefore represents embryonic gastric mucosa. The specialized columnar epithelium of Barrett's esophagus has been considered to have evolved from gastric mucous neck cells. However, although glucagon cells are a feature of the embryonic stomach, neurotensin-immunoreactive cells have not been found in the gastric mucosa. Our study suggests that the specialized columnar epithelium of Barrett's esophagus originates from a very immature multipotent gastrointestinal stem cell.

Aged↗
PubMed1990

Dissimilar trophic effects of cerulein and xenopsin on the rat pancreas.

Cholecystokinin (CCK), gastrin, cerulein, and other analogs are known to stimulate the growth of the rat pancreas. In the present study, we compared the trophic action of a member of this gastrin/CCK family, the amphibian peptide cerulein, with a member of the structurally unrelated neurotensin/xenopsin group, the amphibian peptide xenopsin. For this purpose, 0.56 nmols/kg cerulein, 1.0 nmols/kg xenopsin, or normal saline were injected intraperitoneally three times a day in 28 rats for 3 d. Pancreatic weight, DNA, and incorporation of 3H-thymidine into DNA were determined. In another study, pancreatic weight, DNA, and the polyamines, putrescine, spermidine, and spermine, were determined after a single dose of 2.7 nmol/kg cerulein, 4.5 nmol/kg xenopsin, or saline. The polyamines were measured by reverse-phase HPLC and post-column derivatization. Cerulein increased pancreatic weight, stimulated 3H-thymidine incorporation into DNA, and raised putrescine concentrations significantly, but led to a significant reduction of pancreatic DNA concentration. Xenopsin also stimulated 3H-thymidine incorporation into DNA, but did not affect pancreatic weight, DNA concentration, or the polyamines during the 4 h of the experiment. These findings suggest that cerulein, in the dose and intervals applied, initiated hyperplasia and induced hypertrophy of the pancreas, whereas xenopsin only initiated hyperplasia. These results, together with the dissimilar secretory effects of the two peptide families, may be the expression of a dissimilar mode of action. However, it cannot be excluded that, since cerulein is more potent than xenopsin, the differences also are owing to dosage. We conclude that cerulein and xenopsin, which both have trophic effects on the pancreas, may act by different mechanisms.

Animals↗
PubMed1990

Arteriovenous shunting and cholestasis in hepatic hemangiomatosis associated with metoclopramide.

Diffuse hemangiomatosis of the liver became apparent in a 22-year-old woman while she was receiving medication with metoclopramide and experiencing the well-known adverse effect of the drug, hyperprolactinemia with secondary amenorrhea and galactorrhea. The hemangiomatosis was demonstrated by ultrasonography, computerized tomography, arteriography, and laparotomy with biopsy. When arteriovenous shunting became life-threatening and severe abdominal pain and cholestasis developed, the patient's name was placed on the waiting list for liver transplantation. However, after stopping the medication with metoclopramide, abdominal pain disappeared, cholestasis decreased, and the arteriovenous shunts in the liver closed completely. This course of disease represents either a spontaneous or a drug-induced activation and regression of hepatic hemangiomatosis. However, the long-term metoclopramide medication indicates a potential role of this drug in the promotion of hepatic angiogenesis. Hepatic angiomatosis in the adult seems to be neither a static nor a steadily progressive disorder but a process with active and regressive phases probably induced by a transient imbalance of angiogenic and angiostatic factors. Such a course should be kept in mind when major surgery or liver transplantation for hepatic hemangiomatosis is planned. It seems prudent to obtain a thorough drug history of all patients with hepatic hemangiomatosis. Whether hepatic hemangiomatosis can be drug induced or not, further investigation of the factors involved in hepatic angiogenesis is warranted.

Adult↗
PubMed1990

Morphometry and function of islet cells after different forms of drainage at pancreatic transplantation in rats.

The survival of endocrine cells of the islets is crucial for a successful transplantation of the pancreas in the treatment of diabetes mellitus. In the present investigation, we compared the effect of four techniques of whole pancreas transplantation in rats on the endocrine cells of islets of Langerhans. Impairment of the endocrine function of the pancreas with a decrease in the k value was seen after 6 months in the group with duct ligation, and after 12 months in the groups with latex and ethibloc occlusion. An open pancreatic duct maintains a more stable endocrine function than in duct-ligated or occluded grafts. Fasting plasma insulin and somatostatin were elevated in transplanted rats. Whichever method of transplantation we chose, the cell ratio remained unchanged compared with the control group, even after 12 months. Therefore, only intact islet architecture enables a normal endocrine pancreatic function.

Animals↗