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Biomedical subjects

H Ahlman

Publications and source records attributed to H Ahlman.

At least 217 records · Page 12Linked to original sources

Ultrastructural evidence for an innervation of epithelial enterochromaffine cells in the guinea pig duodenum.

The innervation of the duodenal enterochromaffine cells (E.C.) of the guinea pig was studied at the electronmicroscopic level. Pretreatment with 5-OH-dopamine was performed to visualize catecholaminergic (CA) nervous elements. Near the basement membrane of all examined E.C. in the crypts, bundles of unmyelinated nerve processes were observed, only partly ensheathed in a Schwann cell cover. At least 4 types of processes could be observed. 1) Boutons containing only small clear vesicles, probably cholinergic fibres; 2) boutons with small clear vesicles, and in addition large (greater than 200 nm) granules with a dense matrix (P-type-fibres); 3) boutons with small electron-dense vesicles, probably CA-fibres; and 4) processes with few vesicles but having the appearance of dendrites. No typical synaptic arrangements were observed, but the minimal distance between the E.C. and the nerve bundles was 150 to 250 nm, thus well within the functional limits of the "autonomic gap". Thus epithelial E.C. may be influenced by several types of nervous elements, including CA-fibres.

Adrenergic Fibers↗

Efferent innervation of the small intestine by adrenergic neurons from the cervical sympathetic and stellate ganglia, studied by retrograde transport of peroxidase.

The nervous pathways between the small intestine of cat and guinea pig and various sympathetic ganglia were investigated by the retrograde horse-radish peroxidase (HRP) technique. HRP was injected at multiple sites in the wall of the duodenum and the first third of the jejunum. At 1--5 days after the injections, the HRP reaction product was searched for in various sympathetic ganglia. Not only the coeliac and nodose ganglia, but also the superior cervical, medial cervical, stellate and thoracic ganglia contained HRP-positive nerve cells. Crushing the cervical vagal nerve prevented the occurrence of HRP-reaction in the cervical ganglia, indicating that the HRP was transported from the gut to the cervical ganglia via axons in the vagal nerve. The results demonstrate that the sympathetic ganglia in the neck (sup, and med. cerv. ganglia and stellate ggl.) send efferent fibres to the small intestine.

Animals↗

The vagal release of 5-hydroxytryptamine from enterochromaffin cells in the cat.

Enterochromaffin cells (EC) from the cat duodenum were studied before and after electrical efferent stimulation of the cervical vagi by means of electron microscopy and fluorescence histochemistry according to the Hillarp-Falck technique. From the same animals portal blood plasma was assayed for serotonin (5-HT) at various stages of the nerve stimulation. Within 15 min after the onset of vagal nerve stimulation there was a more than twofold increase of the portal 5-HT levels, which returned to normal after cessation of stimulation. There was also a pronounced reduction in the fluorescence intensity of EC demonstrating a lowered intracellular 5-HT level. Ultrastructurally there was evidence for basal exocytosis as well as for a release of osmiophilic material from the EC directly into the gut lumen after nerve stimulation. Together, these observations strongly suggest a vagally induced 5-HT release from EC in the cat.

Animals↗

Blood flow in the calves during surgery.

The volume flow in the calves was measured by means of plethysmography in 14 patients who had a cholecystectomy and in 3 patients who had a wedge biopsy of the breast. The blood flow increased 100% during abdominal surgery, while no change was observed during the extraabdominal operation. When the legs were placed horizontally during cholecystectomy clear signs of venous pooling were observed. Venous pooling in the calves increased when pillows were placed in the popliteal fossae to prevent over-stretching of the knees. Elevation of the legs 20 degrees in the hip joints decreased the venous stasis considerably. Except for intermittent effects on the circulation caused by strong retraction of the intestines, no clear-cut change in the degree of venous stasis was observed during the course of a cholecystectomy.

Adult↗

Vagal influence on serotonin concentration in enterochromaffin cells in the cat.

The intracellular concentrations of 5-HT in enterochromaffin cells of the jejunum, midgut and ileum of the cat have been estimated by a cytofluorimetric method before and after various periods of peripheral vagal nerve stimulation. The fluorescence intensities in randomized cell samples were measured photometrically after a standard illumination time before and after nerve stimulation. A significant decrease in 5-HT concentration in the enterochromaffin cells all through the small intestine could be demonstrated, which is in support of the hypothesis of a neurogenic release of 5-HT from enterochromaffin cells, possibly caused by vagal adrenergic fibres.

Animals↗

A possible vagal adrenergic release of serotonin from enterochromaffin cells in the cat.

The intracellular concentrations of serotonin (5-HT) in enterochromaffin cells (EC) in the cat small intestine have been studied by a cytofluorimetric method before and after long-lasting efferent vagal nerve stimulation in the neck. Such stimulation induces a decrease of 5-HT in EC of the gut as observed previously. Pretreatment with atropine could not block this decrease, suggesting a noncholinergic mechanism. Pretreatment with a beta-blocking agent, propranolol, or bilateral removal of the superior cervical ganglia could, however, block this 5-HT decrease. Pretreatment with an alpha-blocking agent, phenoxybenzamine, caused an increase in the 5-HT content of EC both with and without nerve stimulation; the reason for this is obscure. The results indicate, that vagal nerve stimulation induces a neurogenic 5-HT release from EC in the gut, and that adrenergic fibres, originating in the superior cervical ganglia, mediate this release probably via a beta-receptor mechanism. Whether or not an alpha-receptor mechanism is also involved cannot be judged at present.

Animals↗

A comparison of small intestinal transit time between the rat and the guinea-pig.

The small intestinal transit was compared in rats and guinea-pigs. A radioactive test substance (polyvinylpyrrolidone labelled with I125) was given directly into the duodenum and the distribution of the isotope in the small bowel was recorded. The small intestine was removed 10 and 20 min after the injection and deep frozen. The frozen intestine was later cut in 20 segments of equal length and the amount of isotope within each of the intestinal segments was recorded by means of a gamma counter. For each animal a propulsion diagram was constructed showing the relative percentage of isotope distributed in the 20 bowel segments. After 20 min the isotope peak was found in the ileo-caecal region in the guinea-pigs whereas 50% of the isotope had passed only half of the small intestine in the rats during the same period of time. The length of the intestine in rats passed by 75%, 50% and 25% of the isotope after 20 min was the same as that found in guinea-pigs 10 min after the injection of the isotope into the duodenum. Thus, there seems to be a marked difference in propulsive activity between rats and guinea-pigs.

Animals↗

Catecholamine-containing nerve fibres in the human abdominal vagus.

The vagal nerve of man has been investigated for the presence of adrenergic nerve fibres using the histochemical fluorescence method of Hillarp and Falck. Following 30-60 min of nerve ligation during surgical operations, the right anterior main trunk (subdiafragmatic level) from one patient, and the anterior nerve of Latarget of 5 patients were found to contain unmyelinated nerve fibres with accumulations of green fluorescent material representing a catecholamine. The observations indicate the presence of adrenergic nerve fibres running caudally in the human vagal nerve, in accordance with similar findings in other mammals, e.g. cats and dogs.

Abdomen↗

The role of calcium channels and serotonin (5-HT2) receptors for tumour cell lodgement in the liver.

The effect of blockade of calcium channels and/or 5-HT receptors on the hepatic lodgement of intraportally injected fibrosarcoma cells was studied in rats. The calcium channel blocker verapamil and the 5-HT2 antagonist ketanserin each had a significant lodgement reducing effect. The pure 5-HT2 antagonist R 56413 was most effective and dose-dependent in its tumour cell lodgement reducing effect. At the highest dose tested (2.5 mg/kg body weight) R 56413 was as effective as thrombocytopenia, indicating that 5-HT is the most important platelet-released product that influences tumour cell lodgement.

Animals↗

Human pheochromocytoma cells studied in culture contain large amounts of DSIP-like material.

Delta sleep-inducing peptide (DSIP)-like immunoreactive (LI) material has been detected in nine different human pheochromocytoma tumors by immunocytochemistry. In primary tumors subjected to indirect immunofluorescence a variable number of tumor cells (25-75%) showed positive cytoplasmic labeling after incubation with DSIP antiserum. Tumor cells grown in culture were strongly labeled by the DSIP antiserum with DSIP-LI concentrated to cell bodies. Electron microscopic immunocytochemistry (immunogold labeling) of pheochromocytoma cells demonstrated DSIP-LI over the dense core of secretory granules. The presence of DSIP-LI in several HPLC fractions from conditioned culture media indicates secretion of DSIP-LI from cultured pheochromocytoma cells. The observations suggest that DSIP-LI is synthesized and stored in secretory granules before release. The different HPLC profiles from each of the tumors may reflect differences in processing or turnover of DSIP-LI in pheochromocytoma cells.

Adrenal Gland Neoplasms↗

Histamine metabolism of gastric carcinoids in Mastomys natalensis.

Pharmacological inhibition of gastric acid secretion and subsequent hypergastrinemia in Mastomys natalensis is an experimental model well suited for the study of gastric carcinoid formation. The genetic susceptibility of Mastomys to develop such tumors is a feature reminiscent of the situation in patients with the MEN-1 Zollinger Ellison syndrome, in whom tumor-induced hypergastrinemia, promotes the development of gastric carcinoids. Chronic hypergastrinemia, induced by the irreversible H2-receptor antagonist loxtidine will cause carcinoid formation in Mastomys already after four to six months. As in humans, gastric carcinoids in Mastomys are mainly composed of enterochromaffinlike (ECL) cells and have low malignant potential. Administration of exogenous gastrin to normal young animals increases the expression of histidine decarboxylase (HDC) mRNA in the oxyntic mucosa within 30 minutes. Endogenous hypergastrinemia, induced by short-time loxtidine treatment (three to 29 days) enhances the expression of HDC mRNA, histamine contents and ECL cell numbers in the oxyntic mucosa. Long-term loxtidine treatment (seven to 21 months) results in sustained hypergastrinemia and tumor formation. Tumor-bearing animals exhibited an increase in HDC mRNA and histamine content in the oxyntic mucosa as well as increased urinary excretion of the main histamine metabolite, tele-methylimidazole acetic acid (MeImAA). Subsequent to cessation of loxtidine treatment for two weeks, all parameters of histamine metabolism were normalized in tumor-bearing animals. These results indicate that gastric carcinoids developing during hypergastrinemia are well-differentiated neoplasms whose histamine synthesis and metabolism is regulated by plasma gastrin.

Animals↗

Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.

The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied.

Animals↗

Somatostatin receptors on neuroendocrine tumors--a way to intraoperative diagnosis and localization.

Intraoperative radionuclide detection using 111In-DTPA-D-Phe1-octreotide was evaluated in five patients with midgut carcinoids and in three patients with recurrent medullary thyroid carcinoma. Three different time intervals (24, 48 and 120 hr) from injection of the radiopharmaceutical to surgery were used. At surgery, suspect tumors were measured by probe in situ and ex vivo after excision. All tissue specimens and blood samples withdrawn during surgery were measured for 111In activity, and tissue/blood activity concentration ratios were calculated. In situ measurements were valuable especially in neck surgery, where the probe was helpful not only in localization of tumors but also in the control of tumor clearance. Ex vivo measurements were helpful in diagnosing tumor tissue. All five patients with midgut carcinoids were somatostatin receptor-positive, while only three out of seven patients with medullary thyroid carcinoma were receptor-positive. The tissue/blood activity concentration ratios and probe measurement ratios were in general higher in patients with midgut carcinoid than in patients with medullary thyroid carcinoma. Of particular interest were the high tissue/blood concentration ratios in all receptor-positive patients at all time intervals studied. This fact suggests a potential role for radiolabelled octreotide in radiotherapy of these tumor types.

Carcinoid Tumor↗