Biomedical subjects

P Kirkegaard

Publications and source records attributed to P Kirkegaard.

At least 91 records · Page 5Linked to original sources

PubMed1986

Immunohistochemical localization of epidermal growth factor in rat and man.

Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands is well documented. The localization of EGF in other tissues is still unclarified. In the present study, the immunohistochemical localization of EGF in tissues from rat, man and a 20 week human fetus were investigated. In man and rat, immunoreaction was found in the submandibular glands, the serous glands of the nasal cavity, Brunner's glands of the duodenum, the Paneth cells of the small intestine, and the tubular cells of the kidney. In the fetus EGF was found in the kidney and in the intestinal Paneth cells. Antisera raised against rat submandibular EGF did not recognize EGF in human tissues, whereas antisera against human urinary EGF worked in rat as well as man. EGF was found only in cells with an exocrine function.

Animals↗

PubMed1986

Effect of antisecretory agents and vagotomy on healing of "chronic" cysteamine-induced duodenal ulcers in rats.

Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference between treated and untreated groups decreased. The morphology of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably being decisive for the prolonged healing. In the treated rats, the mucosa first regenerated with formation of crypts and low villi and subsequently, the Brunner's glands were formed by proliferation from the bottom of the crypts.

Animals↗

PubMed1986

Vasoactive intestinal polypeptide and acetylcholine stimulate exocrine secretion of epidermal growth factor from the rat submandibular gland.

The effect of vasoactive intestinal polypeptide (VIP) and acetylcholine on secretion of epidermal growth factor (EGF) from the rat salivary glands was investigated. VIP in doses of 3 X 10(-10) to 3 X 10(-8) mol/kg per h stimulated secretion of saliva and total output of EGF dose-dependently. Acetylcholine also stimulated salivation and output of EGF. VIP in a dose of 3 X 10(-11) to 3 X 10(-10) mol/kg per h enhanced the stimulatory effect of acetylcholine, but this effect disappeared when the dose of VIP was increased. Adrenalectomy decreased acetylcholine stimulated total output of EGF by approximately 50%, but only by 20% when acetylcholine plus VIP was administered. EGF was localized to the convoluted granular tubules in the submandibular gland, whereas EGF could not be detected in the remaining salivary glands. The results suggest that VIP and acetylcholine cooperate in the control of exocrine secretion from the rat salivary glands. The effect of acetylcholine, however, seems to be partly dependent on circulating catecholamines.

Acetylcholine↗

PubMed1986

Effect of neurotensin and neurotensin fragments on gastric acid secretion in man.

The effect of intravenous infusion of neurotensin (NT) and NT-fragments on pentagastrin stimulated gastric acid secretion was investigated in healthy subjects. Neurotensin was infused in three doses (72, 144 and 288 pmol/kg per h). An N-terminal fragment (NT 1-8), a C-terminal fragment (NT 8-13) and an NT-analogue, substituted at the C-terminal tyrosine residue (Phe11-NT) were infused in two doses (72 and 144 pmol/kg per h). Concentrations of the infused peptides were measured in peripheral venous blood by radioimmunoassay. Plasma levels of NT 1-13, NT 1-8 and Phe11-NT increased in a dose-dependent manner; NT 1-13 to 50 (34-69), 78 (54-113) and 143 (112-242) pmol/l (medians and range) at 72, 144 and 288 pmol/kg per h, NT 1-8 to 405 (340-465) and 1215 (915-1300) pmol/l, and Phe11-NT to 200 (110-245) and 390 (250-410) pmol/l at 72 and 144 pmol/kg per h, respectively. Increases in plasma levels of NT 8-13 could not be detected during the infusion, suggesting that the fragment is rapidly metabolized in man. Neurotensin 1-13 inhibited gastric acid secretion in a dose-dependent manner and the decrease in gastric acid secretion was linearly related to plasma levels of NT 1-13. Neurotensin 1-8 and NT 8-13 inhibited gastric acid secretion only at 144 pmol/kg per h, while the analogue Phe11-NT had no effect. The results showed that the inhibition of gastric acid secretion produced by NT was dose-dependent and linearly related to circulating levels of NT, and that under physiological conditions this effect presumably is elicited by the C-terminal part of the peptide.

Adult↗

PubMed1986

Multiple stenoses of the small intestine by metastatic spread from breast cancer.

We present a patient who had a left mastectomy for breast cancer and 3 years later developed intestinal obstruction due to metastatic spread to the small bowel. The small bowel follow through showed multiple stenoses of the small intestine leading to a variety of differential diagnostic considerations as metastatic spread from breast cancer to the small intestine has not been convincingly documented so far.

Adenocarcinoma, Mucinous↗

PubMed1985

Localization of a new serine protease, ingobsin, in goblet cells in rat, pig and man.

A serine protease, ingobsin, that cleaves Lys-x and Arg-x, has been purified from rat duodenal tissue. By immunohistochemical methods, the enzyme was localized in goblet cells in the small intestine of rat, pig, and man. The immunoreactive cells were most numerous in the proximal part of the intestine. In the electron microscope, the immunoreaction was localized mainly to the rough endoplasmic reticulum of the goblet cells and to the secretion being extruded from the cells.

Animals↗

PubMed1985

Healing of cysteamine-induced duodenal ulcers in the rat.

The mechanism and time for healing of cysteamine-induced duodenal ulcers in rats were investigated. Cysteamine induces a mixture of erosions, ulcers, and penetrating ulcers. These three stages of ulcerations healed in different ways and in different times. Erosions healed within three days by formation of new mucosa from the epithelium of the remaining parts of the crypts of Lieberkühn. The mucosa became completely normal within 15 days. Ulcers healed primarily by a contraction of the circular layer of the external muscle coat, thereby approaching the ulcer edges and reestablishing a complete layer of Brunner's glands in the submucosa. Healing was complete within 15 days. Penetrated ulcers healed very slowly by formation of new epithelium and Brunner's glands from the ulcer edges. The newly formed epithelium was desquamated unless protected by underlying Brunner's glands and the regeneration of these therefore determined the healing of the ulcer. Only a few of these ulcers had healed after 50 days. After 100 and 150 days, approximately 50% had healed, and after 200 days still only 64% had healed. Thus the cysteamine ulcer with destroyed muscle coat has a very prolonged healing and thereby represents a model for a chronic duodenal ulcer which may be of value as a model for testing treatments of duodenal ulcers.

Animals↗

PubMed1985

Adrenergic effects on renal secretion of epidermal growth factor in the rat.

Urinary epidermal growth factor (EGF) has been demonstrated recently to originate from the kidneys. The present study was undertaken to investigate the adrenergic and cholinergic influence on secretion of renal EGF. beta-Adrenergic agonists increased the level of urinary EGF, while propranolol, a beta-adrenergic blocking agent, decreased basal and beta-adrenergic stimulated total output of urinary EGF. Acetylcholine and the anticholinergic agent atropine had no effect on the output of EGF in urine. Also chemical sympathectomy induced by 6-hydroxydopamine reduced the urinary output of EGF. None of the experimental groups had a median serum concentration above the detection limit of the assay. The present study shows that secretion of renal EGF is under the influence of the sympathetic nervous system and release of EGF is stimulated by activation of beta-adrenergic receptors in the kidneys.

Adrenergic beta-Agonists↗

PubMed1985

Adrenergic effects on secretion of epidermal growth factor from Brunner's glands.

The influence of the sympathetic nervous system and adrenergic agonists on flow rate and secretion of epidermal growth factor (EGF) from Brunner's glands has been investigated in the rat. Chemical sympathectomy by administration of 6-hydroxydopamine increased volume secretion and output of EGF from Brunner's glands but depleted the glands of EGF. Infusion of noradrenaline, an alpha-adrenergic agonist, inhibited basal and vasoactive intestinal polypeptide (VIP) stimulated flow rate and output of EGF from Brunner's glands and increased the amount of EGF in the tissue. Vasoactive intestinal polypeptide also increased the amount of EGF in Brunner's gland tissue and this was unchanged after simultaneous infusion of VIP and noradrenaline as well as VIP and isoproterenol, a beta-adrenergic agonist. Isoproterenol had no effect on basal and VIP stimulated secretion of EGF from Brunner's glands. The presence of PAS-positive mucus in Brunner's glands was unchanged during infusion of noradrenaline whereas VIP induced a depletion of Brunner's gland mucus which in turn was prevented by simultaneous infusion of noradrenaline. This study indicates that the sympathetic nervous system influence the volume secretion, output of EGF and mucus content in Brunner's glands probably by activation of alpha-adrenergic pathways.

Adrenergic Agonists↗

PubMed1985

Gas-producing perianal infection.

Five cases of nonclostridial, gas-producing perianal infection are reported and the resemblance to clostridial gas gangrene is discussed. The importance of early diagnosis followed by aggressive surgical debridement and prompt administration of broad-spectrum antibiotics is emphasized.

Abscess↗

PubMed1984

Renal origin of rat urinary epidermal growth factor.

The origin of rat urinary epidermal growth factor (EGF) has been investigated. Unilateral nephrectomy decreased the concentration, total output of EGF and EGF/creatinine ratio by approximately 50%, while the output of creatinine was unchanged. Removal of the submandibular glands and duodenal Brunner's glands, organs known to produce EGF, had no influence on the output of EGF in urine. Renal clearance of EGF exceeded that of creatinine, and after bilateral nephrectomy or bilateral ligation of the ureters, the concentration of creatinine in serum increased, while the concentration of EGF was below the detection limit of the assay. Renal production of EGF was confirmed by immunohistochemistry demonstrating EGF immunoreactivity in the afferent arteriole of the juxtaglomerular apparatus. EGF in the submandibular glands and in urine was found to differ with chromatofocusing and reverse-phase HPLC. At isoelectric focusing the pI of submandibular EGF was 4.8 and 5.4 while that of urinary EGF was 5.3 and 6.4. In conclusion, this study demonstrates that urinary EGF mainly originates from the kidneys and is localized to the renal juxtaglomerular apparatus.

Animals↗

PubMed1984

The stability of gastric acid secretion during prolonged pentagastrin stimulation in man.

Prolonged stimulation with pentagastrin in doses of 100 and 500 ng h-1 kg-1 was performed in nine healthy subjects. A plateau in gastric secretion was reached after 90 min with 100 ng h-1 kg-1 and 500 ng h-1 kg-1 resulted in a secretory plateau after 60 min. When the plateau was reached the acid secretion rate was constant for the rest of the study, that is 4 h after beginning the pentagastrin infusion. Medians and interquartile ranges of acid output were 4.9 (3.7-5.2) and 8.1 (5.8-9.5) mmol of H+/30 min. We conclude that no 'fade' of gastric acid secretion occurs during 4 h of submaximal pentagastrin stimulation in normal subjects, and that the time required for reaching a secretory plateau is dependent on the dose of pentagastrin.

Adult↗

PubMed1984

Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands.

The effect of VIP and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands was investigated in the rat. Vasoactive intestinal polypeptide infused in doses of 10 and 100 ng/kg/h significantly increased epidermal growth factor and bicarbonate output, but the concentrations did not change. Somatostatin infused at doses of 1, 10, 100 and 1000 ng/kg/h against a background of VIP 100 ng/kg/h inhibited in dose-dependent fashion the stimulated epidermal growth factor and bicarbonate outputs from rat Brunner's gland pouches. Also basal secretion was inhibited by somatostatin. Infusion of antisomatostatin serum stimulated Brunner's gland secretion. By immunohistochemical studies of rat duodena, it was found that epidermal growth factor, is almost exclusively present in the secretory cells of Brunner's glands. It is concluded that VIP stimulates secretion of epidermal growth factor and bicarbonate from Brunner's glands, an effect which is inhibited by somatostatin. A possible role for somatostatin in the control of Brunner's gland secretion is suggested.

Animals↗

PubMed1984

Adrenergic effects on exocrine secretion of rat submandibular epidermal growth factor.

The present study was undertaken to investigate the effect of alpha- and beta-adrenergic agonists on secretion of epidermal growth factor (EGF) from the rat submandibular glands and to test the possibility of intestinal absorption of EGF. Alpha-adrenergic agonists increased the concentration of salivary EGF by approximately a hundred times, while the serum concentration of EGF was unchanged. The contents of EGF in the submandibular glands decreased upon administration of the alpha-adrenergic agonist noradrenaline, and this was confirmed on immunohistochemical investigation of the glands. Beta-adrenergic agonists had no effect on secretion of EGF from the submandibular glands. Intestinal absorption of EGF could not be confirmed, as stimulation by noradrenaline with free passage of saliva to the gastrointestinal tract and intrajejunal infusion of EGF had no influence on the concentration of EGF in serum. This study shows that alpha-adrenergic agonists stimulate exocrine secretion of submandibular EGF and that EGF in physiological amounts are not absorbed in the gastrointestinal tract.

Adrenergic alpha-Agonists↗

PubMed1984

Interaction of calcium and gastrin on gastric acid secretion in duodenal ulcer patients.

A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 in doses of 50,200, and 500 ng/kg/h was performed in eight healthy volunteers and in eight patients with duodenal ulcer. The study was repeated on a separate day during intravenous infusion of calcium gluconate (0.1 mmol Ca2+/kg/h). In healthy subjects the acid response to the combined infusion of synthetic human gastrin and calcium did not significantly exceed the response to synthetic human gastrin alone, in contrast with patients with duodenal ulcer in whom the combined infusion did significantly improve acid output compared with infusion of synthetic human gastrin alone. The dose of synthetic human gastrin required for half maximal acid response (D50) was reduced in both groups but significantly more in patients with duodenal ulcer. No difference in serum gastrin concentrations or in serum calcium concentrations were found. It is hypothesised that extracellular calcium plays a role in gastrin stimulated acid secretion in man and that patients with duodenal ulcer are more sensitive to this calcium dependent mechanism than non-duodenal ulcer subjects.

Adult↗

PubMed1984

Effect of secretin and glucagon on Brunner's gland secretion in the rat.

Brunner's gland secretion in response to infusion of secretin and glucagon was studied in the rat. Secretin was infused in doses of 15, 150 and 1500 ng/kg/h. All dose significantly increased bicarbonate and protein output and depleted Brunner's glands of PAS-positive mucin. Bicarbonate secretion was related to plasma secretin concentration, and a marked stimulatory effect of secretin was found in very low, probably physiological, plasma concentrations. Maximal bicarbonate output was obtained at a plasma concentration of secretin about 20 pmol/l. Glucagon was infused at a rate of 1.0 micrograms/kg/h and did not influence secretion rate or cell morphology. Also large doses of 5.0 and 50.0 micrograms/kg/h had no effect on Brunner's gland secretion. It is concluded that secretin in very low plasma concentrations stimulates secretion of bicarbonate, protein and mucus from Brunner's glands in the rat, while glucagon has no effect, and it is suggested that secretin may be involved in the physiological regulation of Brunner's gland secretion.

Animals↗

PubMed1984

Neurotensin induced inhibition of gastric acid secretion in duodenal ulcer patients before and after parietal cell vagotomy.

The influence of the vagal nerve on the inhibitory effect of neurotensin on pentagastrin stimulated gastric acid secretion was investigated in seven duodenal ulcer patients before and after parietal cell vagotomy without drainage. Preoperatively, neurotensin inhibited gastric acid secretion, whereas no effect was found postoperatively. Plasma concentration of neurotensin was identical pre-and postoperatively. This study shows that the inhibitory effect of neurotensin on gastric acid secretion is dependent on an intact vagal innervation of the parietal cell area.

Adult↗

PubMed1984

Characterisation of a novel proteolytic enzyme localised to goblet cells in rat and man.

A proteolytic enzyme, ingobsin , purified from rat duodenal extracts is shown to be localised to intestinal goblet cells of both man and rat. Enzyme positive cells decrease in number from duodenum to colon. The enzyme is a 33 000 Mr protein with an isoelectric point of 5.1. The pH optimum for enzymatic activity is 7.4-8.0. Based on substrate specificity for arg-x, lys-x and to a lesser degree tyr-x, on the effect of diisopropylphosphorofluoride , Trasylol and phenylmethylsulfonylfluoride and on proteolytic activity towards intact proteins, ingobsin is classified as a serine proteinase with endoproteolytic activity.

Animals↗