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H Ahlman

Publications and source records attributed to H Ahlman.

At least 163 records · Page 9Linked to original sources
PubMed1985

Involvement of platelet-released 5-HT in tumor cell lodgement.

Adherence of circulating tumor cells in the microvasculature (lodgement) is a key event in metastasis formation, once cells released from a primary neoplasm have reached the bloodstream. Platelets appear to be involved in tumor cell lodgement, since thrombocytopenia significantly reduces the number of lodged tumor cells. Platelets activated by tumor cells are known to release 5-HT, and therefore the present study was focused on the influence of this amine on hepatic lodgement of intraportally injected fibrosarcoma cells in rats. Lodgement was quantified by labeling of tumor cells with [5-125I]iodo-2-deoxy-uridine. 5-HT levels were simultaneously determined using liquid chromatography with electrochemical detection (LCED) from hepatic areas with lodged tumor cells, as seen in vital microscopy. Injection of tumor cells increased hepatic 5-HT levels twofold (614 +/- 64 micrograms/g) compared with the levels found in rapidly killed (284 +/- 22 micrograms/g) or saline-injected animals (231 +/- 75 micrograms/g). In thrombocytopenia lodgement was reduced by 47% and hepatic 5-HT levels by 52% in comparison with tumor cell-injected controls. Peripheral blockade of 5-HT2 receptors with ketanserin (0.6 mg/kg sc) also reduced lodgement by 28% and hepatic 5-HT levels by 36%, strongly indicating involvement of platelet-released 5-HT in the lodgement process. Immunocytochemical studies of hepatic tissue in untreated rats demonstrated presence of 5-HT only in mast cells, while as early as 15 min after tumor cell injection 5-HT immunopositive nerves were also seen. This implies an active uptake of circulating 5-HT by neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The influence of cholinergic and adrenergic blockade on the portal release of substance P in the cat.

The effect of efferent electrical stimulation of the divided thoracic vagus nerves on the release of substance P-like immunoreactivity (SPLI) into the portal vein was studied in anesthetized cats. Under basal conditions portal SPLI levels were fairly constant. During the first 5 min of vagal stimulation there was a significant increase of the portal plasma levels of SPLI. Since we have demonstrated that infracardiac vagal stimulation causes only minor changes in small intestinal bloodflow, a true vagal neurogenic release of SPLI seems likely. We have shown that SPLI is exclusively localized within feline gut neurons (not the enterochromaffin (EC) cells). Thus, SPLI released into the portal circulation probably represents overflow of transmitter into the circulation. Neither blockade of cholino- or adrenoceptors nor ganglionic blockade influenced the enhanced release of SPLI induced by vagal stimulation, suggesting activation of SP neurons via nonclassical receptors.

Animals↗
PubMed1985

Influence of ketanserin on 5-hydroxytryptamine-induced cerebrovascular spasm in the cat.

In an experimental cat model the leptomeningeal vasculature was studied by a vital microscopic brain window technique. The brain window was connected to a thermostat-regulated pool of Elliot's solution. By air-drying (10 min) of the arachnoid mesothelium access for drugs, applied into the pool, was established to the adventitia of the leptomeningeal vasculature. Application of 5-hydroxytryptamine (5-HT) (10(-6)-10(-4) M) caused dose-dependent contractile responses (morphometry of outer vessel diameter) of both arteries and veins of three different sizes (large, 200-300 microns; medium, 50-150 microns; small, 30-50 microns). A well-reproducible contractile response was obtained at challenge with 5-HT (10(-4) M) from the various vascular beds with most pronounced effects on the arterial side. If the animals were pretreated with peripheral blockade of serotonergic (5-HT2) receptors (ketanserin 0.3 mg/kg i.v.), challenge with 5-HT (10(-4) M) elicited no significant vascular responses on either the arterial or venous sides. Vital microscopy further visualized capillary beds after ketanserin pretreatment that were not seen under control conditions.

Animals↗
PubMed1985

Serotonin and carcinoid tumors.

The enterochromaffin (EC) cell system is distributed throughout the entire gastrointestinal tract. Enterochromaffin cells are the major source of intestinal serotonin (5-HT), but separate subpopulations of EC cells may synthesize and store peptides as substance P (SP), motilin, and enkephalin as well. Of special interest is that 5-HT and SP, which may coexist in EC cells, have several functional similarities, i.e., inhibition of gastric acid secretion, stimulation of intestinal motility, and secretion of water and electrolytes. Carcinoid tumors are derived from the gut endocrine system. Depending on site of origin, carcinoids are divided into foregut, midgut, and hindgut derivatives with different clinical symptoms. A common biochemical feature of midgut carcinoids is the production of 5-HT and SP. Histochemically, midgut carcinoids are characterized by the argentaffin reaction--a direct reduction of silver salts owing to 5-HT. Specific antisera for the immunocytochemical demonstration of secretory products are available as well. Despite their relative infrequency, carcinoids are the most common small intestinal tumors. The common appendix tumors generally have a benign clinical course, whereas the small intestinal tumors have different growth patterns and frequently metastasize with increasing size, and may thus give rise to the carcinoid syndrome (diarrhea, facial flush, right-sided cardiac valvular disease, and asthma). Carcinoid symptoms first appear when hepatic inactivation of 5-HT is exceeded, unless the carcinoid has an extraintestinal localization, for example, ovarian lesions may elicit symptoms in the absence of hepatic disease owing to direct secretion into systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

APUD Cells↗
PubMed1985

The pentagastrin test in the diagnosis of the carcinoid syndrome.

Serotonin (5-HT) and substance P (SP) were assayed in peripheral blood in patients with known midgut carcinoids and hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal response was evaluated by two provocation tests, pentagastrin (PG) injection or calcium infusion. Pentagastrin caused flushing and gastrointestinal symptoms and elevated levels of circulating 5-HT, but not of SP. Pretreatment with a 5-HT2 receptor blocking agent (ketanserin) alleviated gastrointestinal symptoms but had no influence on either 5-HT release or PG-induced flushing. Calcium infusion induced carcinoid symptoms in only two of six patients, which were associated with elevated 5-HT levels (whereas elevated SP levels were seen in only one patient). We conclude that 5-HT is important for the development of gastrointestinal symptoms but not of flushing. Ketanserin may alleviate gastrointestinal symptoms but does not influence PG-induced release of 5-HT. Substance P and 5-HT do not seem to share a common release mechanism. It appears that PG testing is superior to calcium infusion as a provocative test in patients with the carcinoid syndrome.

Carcinoid Tumor↗
PubMed1985

An in vivo model for the simultaneous study of motility of the gallbladder, sphincter of Oddi and duodenal wall in the cat.

An in vivo model for the simultaneous study of motility of the gallbladder, sphincter of Oddi and the duodenal wall in species with an intraduodenal location of the sphincter has been developed. Gallbladder motility is registered by manometry, while trans-sphincteric flow and duodenal wall motility are recorded by perfusion methods. The sphincter of Oddi proper is totally uninfluenced by any mechanical procedures since the outflow of fluid is collected via a funnel-shaped human femoral vein graft fixed to the duodenal mucosa by tiny sutures peripheral to the sphincteric muscle. The motility of the duodenal wall influences the flow of saline through a small feline vein graft inserted across the duodenal wall. The method is described in detail as well as nerve stimulation experiments and some pharmacological tests (e.g. infusion of substance P) to demonstrate the usefulness of the method. With this method the physiology and pharmacology of this region can be investigated in species, which, like man, have an intraduodenal location of the sphincter of Oddi.

Ampulla of Vater↗
PubMed1985

The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine.

Endoluminal release of serotonin (5-HT), substance P (SP), and motilin was quantitated after thoracic vagal nerve stimulation in the cat. In duodenum and jejunum, simultaneous release of these compounds was observed. In contrast, vagal stimulation did not augment the rate of luminal secretion of either 5-HT or SP in the distal ileum. Immunohistochemical studies demonstrated 5-HT in both enterochromaffin (EC) cells and nerves throughout the small bowel. However, we were unable to visualize any SP-containing EC cells in the cat, which suggests that the source of luminal SP in this species must be intramural nerves.

Animals↗
PubMed1985

On the mode of action of the pentagastrin test in the carcinoid syndrome.

Provocation with pentagastrin (PG) (0.6 micrograms/kg intravenously) causes a release of serotonin (5-hydroxytryptamine (5-HT] in excess of the metabolizing capacity associated with carcinoid symptoms and a moderate fall in systemic arterial blood pressure in patients with midgut carcinoids and hepatic metastases. In this study PG also caused a release of 5-HT into portal circulation of anesthetized cats with stable peripheral levels of 5-HT in whole blood, indicating an effective hepatic metabolization. A similar response was obtained in the same animal when the PG test was repeated after 3 h. PG provocation was also performed in animals before and after adrenalectomy. Adrenalectomy seems to prevent the PG-induced release of 5-HT into portal circulation, indicating involvement of an adrenal mechanism. PG does not induce 5-HT release from cell suspensions of midgut carcinoid tumors, but such release was induced by incubation with adrenoceptor agonists. These findings indicate the presence of adrenoceptors on carcinoid tumor cells. The mode of action of the PG test may therefore be activation of such adrenoceptors by catecholamines, released from the adrenal medulla at the fall of arterial blood pressure at PG provocation.

Adrenalectomy↗
PubMed1985

The pentagastrin test in the diagnosis of the carcinoid syndrome. Blockade of gastrointestinal symptoms by ketanserin.

The levels of 5-hydroxytryptamine (serotonin, 5-HT) and substance P (SP) were assayed (using high performance liquid chromatography-electron capture and radioimmunoassay methods) in the peripheral blood of 17 patients with known mid-gut carcinoids, 16 of whom had hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal changes induced by two provocation tests, intravenous pentagastrin (PG) and calcium infusion, were compared. Pentagastrin caused flushing in all the patients, induced gastrointestinal symptoms in all but one of the patients with hepatic involvement, and universally elevated circulating 5-HT levels. Pretreatment with a 5-HT2-receptor blocking agent, ketanserin, abolished the gastrointestinal effects but had virtually no influence on either 5-HT levels or flushing induced by intravenous pentagastrin. In contrast, calcium infusion induced carcinoid symptoms in only two of six patients, and this was consistently associated with stimulation of circulating serotonin levels. The authors conclude that 1) 5-HT may be responsible for the gastrointestinal symptoms in carcinoid patients, but it does not seem to play any role in flushing; 2) ketanserin may be a useful therapeutic agent in alleviating gastrointestinal symptoms in carcinoid patients; 3) differential responses to PG suggests that SP is released from a site different from that of 5-HT; 4) it is possible that SP may contribute to the mediation of flushing, but it cannot be the sole agent causing this symptom; and 5) the pentagastrin test with measurements of 5-HT levels in peripheral blood seems to be superior to calcium infusion as a provocative test in documenting the diagnosis of carcinoid disease.

Aged↗
PubMed1984

The importance of 5-HT for tumor cell lodgement in the liver.

Arrest and lodgement of circulating tumor cells in the microvasculature is a prerequisite for metastasis formation. Aggregation of activated platelets and subsequent release of bioactive substances seem to influence the lodgement process. Since thrombocytopenia has been shown to reduce lodgement and since 5-HT is one of the compounds released from activated platelets, the present investigation was directed toward the influence of this amine on tumor cell lodgement in the liver after intraportal injection of fibrosarcoma cells. Lodgement was quantitated by an isotope technique with simultaneous measurements of 5-HT levels by a LCEC technique in rat liver biopsies from areas with lodged tumor cells as observed with vital fluorescence microscopy. To test the importance of 5-HT released from platelets, thrombocytopenia was induced with anti-platelet serum in one experimental group, while animals in another group were treated with ketanserin (a selective 5-HT2 receptor blocking agent). Animals given tumor cells alone showed a two-fold increase in 5-HT levels compared with animals injected with saline, indicating a relation between 5-HT release and tumor cell lodgement. In thrombocytopenic animals lodgement was reduced to 53% (5-HT levels reduced to 50%) of tumor-cell-injected controls. Ketanserin treatment reduced tumor cell lodgement to 72% (5-HT levels to 63%). The results indicate that 5-HT is one of the substances released from activated platelets and that 5-HT is involved in tumor cell lodgement.

Animals↗
PubMed1984

Effects of extrinsic denervation on net water transport and motility of the feline gallbladder in vivo.

The influence on the concentrating ability of the gallbladder after extrinsic denervation was studied in anesthetized cats, previously subjected to truncal vagotomy, and/or celiacectomy , and compared with sham-operated controls. Net water absorption was studied by perfusion techniques. Acute experiments were performed under basal conditions and alpha-adrenoceptor stimulation (iv infusion of norepinephrine (NE), 1 micrograms/kg X min). Gallbladder biopsies were studied by fluorescence microscopy to visualize and quantitate catecholamines. Three weeks after celiacectomy basal absorption had decreased significantly. In the short-term vagotomy group no changes were demonstrated. However, in the long-term vagotomy group there was a fourfold increase in absorptive capacity, which decreased to control levels after alpha-adrenoceptor blockade (phentolamine 1 mg/kg iv). Long-term vagotomy with subsequent celiacectomy caused no significant changes. Infusion of NE increased net water absorption by 70 +/- 16% in all experimental groups except in long-term vagotomized animals, where the high basal absorption was not further augmented. One hour after NE infusion controls returned to basal absorption rate, while denervated cats remained at stimulated levels. In long-term vagotomized gallbladders there were morphological signs of adrenergic proliferation (increased total number of nerve terminals, sprouting, and elevated levels of intraneuronal NE). In conclusion these results suggest that the adrenergic nervous system is important for full absorptive capacity of the gallbladder. The increased absorption after long-term vagotomy, abolished after alpha-adrenoceptor blockade, might well be explained by the parallel adrenergic proliferation. This hypothesis was further corroborated in animals with long-term vagotomy, where subsequent surgical adrenergic denervation restored basal absorption to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1984

Influence of anaesthesia on blood flow to the calves during surgery.

The blood flow to the calves during abdominal surgery under different kinds of general anaesthesia was measured by strain gauge plethysmography in 12 patients. The volume flow increased 100% during surgery in both light and deep anaesthesia, caused by a decrease in peripheral resistance. The increase in volume flow could partly be explained by the anaesthesia itself, possibly induced by the use of a nitrous oxide-oxygen gas mixture. The surgical procedure caused a further increase in volume flow. Possible underlying mechanisms are discussed.

Adult↗
PubMed1984

The uptake of 5-hydroxytryptamine in endothelial cells cultured from the pulmonary artery in rats. A cytochemical study.

Endothelial cells from the rat pulmonary artery were cultured and identified ultrastructurally and immunocytochemically by the presence of factor VIII antigens. Monolayers of cultured cells were treated according to the Hillarp-Falck technique and studied cytofluorimetrically to estimate intracellular serotonin (5-HT) levels. An uptake of 5-HT from the incubation medium was demonstrated at a concentration of 10(-3) M. However, after inhibition of monoamine oxidase (nalamide 5 X 10(-4) M) to prevent intracellular degradation of the amine an uptake could be demonstrated at 10(-5) M. The amine uptake into endothelial cells utilizes an active pumpmechanism, since it was effectively antagonized by either imipramine (10(-4) M) or ouabain (10(-5) M). These in vitro findings contrast earlier cytofluorimetric in vivo studies, where 5-HT uptake predominantly occurred in interstitial mast cells.

Animals↗
PubMed1984

Further evidence for the presence of subepithelial nerve cells in the rat ileum--an immunohistochemical study.

Earlier we observed electronmicroscopically an unidentified but neuron-like subepithelial cell in the crypts of the rat ileum. We have now studied some immunocytochemical characteristics of similar cells in the fluorescence microscope by indirect immunofluorescence. Three markers for neuronal tissues were used: 1) Monoclonal Thy-1-antibodies, demonstrated previously to recognize surface antigens of thymus-derived cells and nervous tissue; 2) Tetanus toxin, which binds to the GT1 ganglioside receptor of nerve cells, and to some other neuronal receptor; and 3) Anti-Protein I-IgG, which is monospecific for Protein I located in synaptic vesicle membranes. The various antisera used for secondary incubations all reacted with leucocytes and other connective tissue cells in the villous cores. When the specific primary antisera of Thy-1 and Protein I, and tetanus toxin, were included, a small number of spindle-shaped cells with two processes, extending just beneath the basal lamina of the epithelium, was observed. These cells had a similar location and appearance as the neuron-like cells observed electronmicroscopically and may be identical with these cells. These results give further evidence that cells with neuron-like characteristics are present in the mucous layer of the small intestine.

Animals↗
PubMed1984

Effect of extrinsic denervation on the rate of net water transport of the feline gall bladder.

The influence on the concentrating ability of the gall bladder after extrinsic denervation was studied in anaesthetised cats, previously subjected to truncal vagotomy and/or coeliacectomy , and compared with sham operated controls. Net water absorption was studied by perfusion techniques. Acute experiments were performed under basal conditions and alpha-adrenoceptor stimulation (intra-arterial infusion of noradrenaline). Gall bladder biopsies were studied by fluorescence microscopy and cytofluorimetry to visualise and quantify catecholamines. Three weeks after coeliacectomy basal absorption had decreased significantly. In the short term vagotomy group no changes were shown. In the long term vagotomy group, however, there was a four-fold increase in absorptive capacity, which decreased to control levels after alpha-adrenoceptor blockade (phentolamine). Long term vagotomy with subsequent coeliacectomy caused no significant changes. Infusion of noradrenaline increased net water absorption by 60 +/- 11% in all experimental groups except in long term vagotomised animals, where the high basal absorption was not further augmented. One hour after noradrenaline infusion controls returned to basal absorption rate, while denervated cats remained at stimulated levels. In long term vagotomised gall bladders there were morphological signs of adrenergic proliferation (increased total number of nerve terminals, sprouting and raised levels of intraneuronal noradrenaline). These results suggest that the adrenergic nervous system is important for full absorptive capacity of the gall bladder. The increased absorption after long term vagotomy, abolished after alpha-adrenoceptor blockade, might well be explained by the parallel adrenergic proliferation. This hypothesis was further corroborated in animals with long term vagotomy, where subsequent surgical adrenergic denervation restored basal absorption to control levels.

Absorption↗
PubMed1984

Is 5-HT a mediator in the motor control of the feline pylorus?

Since serotonin (5-HT) is a potent spasmogen of pyloric smooth muscle in vivo, and since it is released on electrical stimulation of extrinsic nerves to the gut, the amine may mediate the excitatory motor responses elicited by vagal or splanchnic stimulation. In this study in cats intra-arterial administration of 5-HT to the stomach evoked a dose-dependent pyloric contraction, which was efficiently antagonized by Ketanserin, a peripheral 5-HT2 receptor antagonist. Such treatment did not affect the vagally or splanchnically induced pyloric motor responses, whereas the blood pressure reaction on splanchnic stimulation was greatly reduced. Therefore, 5-HT does not seem to be essential for the extrinsic neural control of pyloric motility. On the other hand, by means of immunocytochemistry, using a 5-HT antiserum, varicose nerve fibres with tryptamine-like immunofluorescence were demonstrated not only in the myenteric plexus and circular muscle layer but also in vascular nerve terminals of the feline pylorus. The function of these tryptamine-containing nerves is still unclear.

Animals↗
PubMed1983

Amines of the mucosal mast cell of the gut in normal and nematode infected rats.

Infection with the nematode N. brasiliensis is accompanied by a marked increase of the number of mucosal mast cells (MMC) and the mucosal content of histamine and 5-hydroxytryptamine (5-HT). We compared amine levels, determined by ion exchange and high performance liquid chromatography (HPLC) with numbers of MMC and enterochromaffin cells (ECC). Furthermore, we measured 5-HT cytofluorometrically in individual MMC and ECC. The cellular distribution of 5-HT was studied immunohistochemically. Our results corroborate previous findings that histamine is stored in MMC. Quotients between histamine content and numbers of MMC decreased throughout the period of worm expulsion, followed by a recovery, suggesting a histamine release during this defense reaction. The HPLC analysis gave no evidence for a storage of dopamine in MMC. ECC and MMC of normal and infected rats showed a formaldehyde induced fluorescence and 5-HT immunoreactivity. The formaldehyde induced fluorescence of MMC from normal rats was about 10% that of ECC, but MMC exceeded ECC three times by numbers. These findings suggest that a considerable proportion of the intestinal 5-HT in the normal rat is stored in MMC. ECC numbers did not change during the infection and their content of 5-HT was unchanged, as judged by cytofluorometry. The cytofluorometric measurements showed that the intensity of the monoamine fluorescence from the MMC of infected animals was about three times as high as that of controls. It was concluded that the increased tissue levels of 5-HT was due to both an increase in MMC numbers and an increase in the 5-HT content of individual MMC. The results suggest a different role for histamine and 5-HT in the defense reaction towards the nematode infection.

Animals↗