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Biomedical subjects

H Ahlman

Publications and source records attributed to H Ahlman.

At least 19 recordsLinked to original sources

Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth?

The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF-I-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-I. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-I-immunoreactive component eluting in the position of rhIGF-I, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.

Adult

Effect of substance P on detrusor muscle in rats with diabetic cystopathy.

Diabetic cystopathy (DCP) is a well known complication in diabetes mellitus (DM). In the present experimental study, DM was induced in rats by streptozotocin and DCP was confirmed on cystometry. In vitro studies on detrusor strips from diabetic rats showed an increased contractile response to substance P (SP) compared with controls, indicating denervation supersensitivity. A decreased response to capsaicin in diabetic detrusor strips indicated a decreased neuronal content of SP or a diminished number of SP-containing sensory nerves. This suggests that DM induces alterations in nerves containing SP which may be at least partly responsible for sensory loss and the development of DCP.

Animals

The effects of splanchnic nerve stimulation on the plasma levels of serotonin and substance P in the portal vein of the cat.

The blood levels of serotonin (5-HT) and substance P (SP) in the portal vein were studied after splanchnic nerve stimulation in the cat. The portal levels of both substances were studied before, during and after splanchnic nerve stimulation. There was a twofold increase in 5-HT during stimulation whilst the SP concentration remained unchanged. These results suggest that the nervous control of the amine release into the portal stream and the mechanism that regulates the release of the polypeptide is not the same.

Animals

The effect of transmural field stimulation on the serotonin content in rat duodenal enterochromaffin cells--in vitro.

The effect of transmural field stimulation (TFS)--in vitro--on the sertonin (5-HT) content in enterochromafffin cells (EC) in rat duodenum was studied with a cytofluorimetric method. TFS caused a significant 25% decrease of 5-HT in EC. The presence of tetrodotoxin or d,1-propranolol in the stimulation bath antagonized the effect of TFS. In biopsies from rats pretreated with 6-OH-dopamine TFS had no effect of the 5-HT content in EC. The results of the present study strongly suggest, that the TFS induced decrease in 5-HT content is due to a direct neural, probably beta-adrenoceptor mediated, influence on the EC.

Adrenergic Fibers

The vagal control of the feline pyloric sphincter.

In acute experiments on cats in chloralose anesthesia the effects of efferent and afferent electrical stimulation of the cervical vagi on an applied constant flow of saline through the feline pylorus was studied. The motor activity of the stomach was recorded simultaneously with a volume recording technique. Efferent cervical vagal stimulation caused a decrease in the transpyloric flow and an increased gastric motor activity. In a few animals the decreased transsphincteric flow was preceded by a short period of increased flow. When the transpyloric flow was reduced by splanchnic nerve stimulation or a noradrenaline infusion, vagal nerve stimulation induced an increased flow through the pylorus indicating the presence of relaxatory fibres to the pylorus within the vagi. Electrical stimulation of the central end of the ipsilateral vagal nerve in the neck, with the contralateral vagal verve left intact, resulted in a decreased transpyloric flow and relaxation of the stomach. This response could be induced with or without intact splanchnic nerves, and disappeared when the intact contralateral vagus was cut. It is concluded that the vagi mediate both excitatory and inhibitory fibres to the pyloric sphincter in the cat. A vago-vagal excitatory reflex to the pylorus can be elicited by afferent vagal nerve stimulation together with a vago-vagal relaxatory response of the stomach.

Afferent Pathways

The effect of propranolol on the serotonin concentration in the portal plasma after vagal nerve stimulation in the cat.

Efferent cervical vagal nerve stimulation in the cat caused a marked increase of the portal plasma 5-HT concentration. This increase was more than two-fold within 15 min of stimulation. After cessation of stimulation portal plasma 5-HT returned to basal levels within 10 min. Treatment with the beta-adrenoceptor antagonist propranolol, in various doses (0.1-2 mg/kg b.wt.), did not abolish but significantly reduced the response to vagal stimulation, particularly during the final part of the stimulation period. The results confirm the existence of a beta-adrenoceptor-mediated release of 5-HT, but also suggest that other mechanisms for 5-HT release may be involved in the response on vagal nerve stimulation.

Adrenergic beta-Antagonists

Substance P-, VIP-, and enkephalin-like immunoreactivity in the human vagus nerve.

The human vagus nerve has been investigated for the presence of substance P (SP), vasoactive intestinal polypeptide (VIP), and enkephalin (ENK) using immunohistochemistry. After 0.5-4 hr of nerve ligation during surgical operations two right thoracic main truncs, two anterior subdiaphragmal trunks, and four anterior nerves of Latarjet were found to contain accumulation of immunoreactive material in nerve fibers above the ligation. Very high numbers of SP-, medium numbers of ENK-, and low number of VIP-immunoreactive fibers were seen. The relative proportions were similar at all levels studied. These data thus indicate the presence and axonal transport of SP-, ENK-, and VIP-like peptides in the human vagus nerve. Our observations in humans correlate well with results obtained from other species. Thus gastrointestinal vagal sensory mechanisms may be mediated by SP (and possibly VIP) and some motor mechanisms by ENK.

Endorphins

Cancer risk in extensive ulcerative colitis.

Two hundred thirty-four patients with extensive ulcerative colitis from the city of Göteborg, Sweden have been followed up and the cumulative risk of development of cancer of the large bowel was estimated. These patients constitute all persons in this region who developed an extensive ulcerative colitis between 1951 and 1974. All patients were followed up until December 1975. The mean observation time was 8.5 years, median value six years. Fifteen patients developed carcinoma of the large bowel. Five of the 15 patients were still alive in December 1975. The expected number of colorectal carcinomas in a matched reference group was 0.49. The cumulative incidence of carcinoma 25 years after the onset of colitis for the whole group of patients was 34% and for those who developed the disease before 25 years of age it was 43%.

Adult

The release of serotonin from rat duodenal enterochromaffin cells by adrenoceptor agonists studied in vitro.

The serotonin (5-HT) content of enterochromaffin cells (EC) was studied by a cytofluorimetric method in biopsies from rat duodenal mucosa after in vitro incubation with different adrenoceptor agonists and antagonists and acetylcholine (ACh). Noradrenaline (NA), Adrenaline (A) and Isoprenaline (IP) caused a decrease of 5-HT in EC down to 40--60% and for NA and A this effect was concentration-dependent. The effect was antagonized by d,1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine indicating that the 5-HT release from EC is probably mediated via a true beta-adrenoceptor mechanism possibly of the beta2 type. ACh also decreased the 5-HT content of EC but was much less potent than the adrenergic substances. Dopamine (DA) had no effect.

Acetylcholine

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