PubMed Health⌕ Search

Biomedical subjects

J Axelson

Publications and source records attributed to J Axelson.

At least 37 records · Page 2Linked to original sources
PubMed1998

The inhibitory effect of an EGF receptor-specific tyrosine kinase inhibitor on pancreatic cancer cell lines was more potent than inhibitory antibodies against the receptors for EGF and IGF I.

CONCLUSION: Epidermal growth factor (EGF) increased the cell number of the two pancreatic cancer cell lines, MiaPaCa-2 and LN-36, in vitro. A blockade of the EGF-R tyrosine kinase with tyrphostin was more efficient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-1-R initially decreased the cell number that later was followed by an increase in LN-36. BACKGROUND/AIM: The receptors and ligands of EGF and insulin-like growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissue. The aim of the present experiments was to study the effects of EGF and IGF-1 on the cell number in two pancreatic cancer cell lines. MATERIAL AND METHODS: MiaPaCa-2 cells were grown in 0.2% fetal calf serum (FCS) and the newly established LN-36 cells in serum-free medium (SFM). The cell number was measured with the XTT method. The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56. RESULTS: MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8) M or higher concentrations a dose-response pattern was seen. Administration of B56 to MiaPaCa-2 decreased the cell number by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increase in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and increased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduced the cell number by 10%. The LN-36 cell line responded to EGF with an increased cell number with a maximum at 5 x 10(-9) M after 96 h. B56 reduced the cell number by 90% at 10(-5) M, with less effect during stimulation with EGF. In contrast to B56, the inhibiting EGF-R-Ab in the same experiment did not reduce the cell number. LN-36 responded to IGF-1 with an increased cell number, but EGF-stimulated growth was not influenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppressed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.

Antibodies↗
PubMed1998

[Combination therapy in oncology (multimodal treatment) in pancreatic tumors].

The majority of patients with pancreatic cancer have systemic disease already at diagnosis, and nearly all patients will develop recurrence following radical resection. Thus, surgical treatment alone is insufficient. The paper focuses on adjuvant multimodal treatment and reviews the current status of pre- and postoperative chemoradiation, intraoperative radiotherapy (IORT), adjuvant chemotherapy, and regional infusion therapy. Studies in this area are hampered by often being non-randomized and with too few patients included. Overall there presently is no adjuvant multimodal treatment which can be suggested for routine use. However, two ongoing prospective randomized studies (ESPAC-1 and an EORTC study) will have enough statistical power to give reliable information on the topic. It is hoped that these and other studies will form the basis for further proper clinical trials on multimodal treatment in pancreatic cancer with the aim at long last to improve the extremely poor survival in these patients.

Adenocarcinoma↗
PubMed1998

An evaluation of the influence of devazepide and CCK-8S on the intact and resected rat liver.

BACKGROUND: Recently, it has been shown that infusion of the CCK-A receptor antagonist devazepide induced proliferation of hepatocytes and bile duct epithelium in the rat liver. The aim of this study was to further evaluate the influence of devazepide and sulfated cholecystokinin-8 (CCK-8S) on the intact rat liver and rat liver after resection. METHODS: In the first experiment, either saline or devazepide was injected subcutaneously twice daily to rats for 18 and 36 h and 3 and 7 days. In the second experiment, a 70% liver resection was followed by infusion of either DMSO, devazepide, saline or CCK-8S for 2 or 7 days. Prior to sacrifice, all rats received 1 mCi/kg of tritiated thymidine intraperitoneally. The liver was excised and the contents of protein, DNA and water and incorporation of tritiated thymidine were measured. RESULTS: Intermittent injections of devazepide increased the liver protein content after 36 h, followed by a decrease after 7 days. The weight, DNA content or cell proliferation was not affected. Two days after liver resection hyperCCKemia was evoked, which was less prominent after 7 days. Devazepide lowered the plasma concentration of CCK, while the infusion of CCK-8S resulted in extremely high concentrations at both time points. The DNA synthesis measured by thymidine incorporation was increased by devazepide on day 2, whereas the weight or protein and DNA contents of the liver were not influenced. CCK-8S infusion decreased the body and liver weight throughout the study, and the protein and DNA contents after 7 days. CONCLUSIONS: Intermittent devazepide treatment did not affect the intact liver. Devazepide increased the DNA synthesis 2 days after liver resection but was without other influences on the liver regeneration. CCK-8S induced decreased body weight with ensuing negative effects on the liver regeneration. Neither devazepide nor CCK seem to be of any therapeutic use after liver resection or liver failure.

Animals↗
PubMed1997

Stimulation with cholecystokinin leads to increased ratio between mRNA levels for anionic and cationic trypsinogen in rat pancreas.

An increased ratio between serum levels of immunoreactive anionic and cationic trypsin is a common finding in many forms of pancreatic disease. Experimental studies have shown that increased stimulation with cholecystokinin (CCK) leads to an increase in the ratio between the pancreatic content of anionic and cationic trypsin. To study whether this effect is caused by increased pancreatic synthesis of anionic trypsin in relation to cationic trypsin we studied the levels of mRNA for anionic and cationic trypsinogen in pancreatic extracts from rats exposed to increased CCK levels through chronic subcutaneous administration of CCK. Northern blot and slot blot hybridization techniques were used. The ratio between mRNAs for anionic and cationic trypsin was significantly higher in CCK-treated rats: median level, 2.04 (range, 1.33-4.08) versus a median level of 1.15 (range, 0.97-2.17) in the control group: P < 0.01. These findings support the view that chronic CCK stimulation leads to the increased synthesis of anionic trypsinogen compared to cationic trypsinogen.

Animals↗
PubMed1997

Epidermal growth factor induces cell proliferation in mouse pancreas and salivary glands.

Epidermal growth factor (EGF) is a mitogenic stimulus in many tissues and occurs in large amounts in the pancreas and salivary glands. Whether EGF is mitogenic in the pancreas is controversial, and the EGF effect has not been studied in the salivary glands. Therefore, the aim of the present study was to investigate the possible effects on the pancreas and parotid and submandibular glands at different time intervals after exogenous EGF administration. Human recombinant EGF was infused subcutaneously by osmotic minipumps in three groups of mice (for 1, 3, and 7 days, respectively) at a dosage of 10 micrograms/kg/h (1.6 mumol/kg/h). Tritiated thymidine was infused intraperitoneally by osmotic minipumps for the same time periods, but only for the last 3 days in the 7-day group. After 1 day the pancreas increased in weight and the increase persisted throughout the study. No effect was seen on the parotid or submandibular gland wet weight. A slight transient increase in pancreas protein content was observed, whereas amylase content was unaffected. The labeling index of serous and ductal cells in the parotid gland increased from the third day. After 7 days, all cell types studied in the pancreas and parotid and submandibular glands were in a hyperproliferative state. The results show that EGF evoked a strong proliferative response on all cell types studied in the pancreas and parotid and submandibular glands.

Animals↗
PubMed1997

Biliodigestive shunt evokes hyperCCKemia and trophic effects in the rat pancreas, but not in the liver or gastrointestinal tract.

The influence of bile on the release of cholecystokinin (CCK) and, thereby, on the regulation of exocrine pancreatic function and growth is unsettled. The aim of this study was to elucidate the effect of long-term diversion of bile from the upper small intestine of CCK release and on the pancreas, liver, and gastrointestinal tract. A surgical biliodigestive shunt was performed in rats, diverting the bile flow directly to the middle of the small intestine. The animals were killed after 4 or 12 weeks. Plasma CCK and trophic effects on the pancreas, liver, and gastrointestinal tract were determined, as were the trypsin and chymotrypsin contents in the intestine. The CCK concentration in plasma increased 10-fold at both time points studied. The pancreas doubled its weight from 4 weeks onward. Also, pancreatic protein, DNA, and amylase contents were increased throughout the study. The liver and gastrointestinal tract were unaffected. Intraluminal bile plays a role in the feedback regulation of CCK release and is involved in this way in the control of pancreatic growth but has no similar effects on the liver or gastrointestinal tract.

Amylases↗
PubMed1997

Total parenteral nutrition influences both endocrine and exocrine function of rat pancreas.

The aim of this study was to examine the effect of total parenteral nutrition (TPN) on the endocrine and exocine function of the pancreas. Endocrine function was investigated using an intravenous glucose tolerance test (IGTT) in rats with TPN for 7 or 14 days. Exocrine function was evaluated by measuring amylase secretion from isolated acini as well as pancreatic weight, water content, protein, and enzymes after 7 days of TPN. When the TPN rats were compared with the controls, the glucose tolerance curve after an IGTT was unchanged, the basal plasma insulin levels were slightly lower and the insulin secretory response to intravenous glucose was markedly impaired. No differences could be seen between the insulin response after 7 days and that after 14 days of TPN. The weight of pancreas, the total content and concentration of pancreatic protein, and the total amylase content of the pancreas were lower, whereas the total content of both chymotrypsin and trypsin was higher. The concentration of DNA remained intact, whereas the total DNA content decreased. The levels of lipolytic enzymes, except for carboxylesterlipase, were unaffected. After TPN treatment, the insulin secretory response to glucose is impaired, the exocrine pancreas is hypoplastic and the storage pattern of pancreatic exocrine enzymes is altered.

Amylases↗
PubMed1997

Total parenteral nutrition affects the tropic effect of cholecystokinin on the exocrine pancreas.

BACKGROUND: Cholecystokinin (CCK) exerts trophic effects on the exocrine pancreas. Total parenteral nutrition (TPN) results in hypotrophy of the pancreas. The present study aimed to examine the effect of exogenous and endogenous CCK during TPN. METHODS: Seventy-two Sprague-Dawley rats were orally fed or given TPN after pancreaticobiliary diversion (PBD) and were infused with CCK-8S or the CCK-receptor antagonist devazepide for 7 days. RESULTS: Infusion of CCK and PBD caused hyperCCKemia, whereas TPN did not influence the concentration of plasma CCK. The reduced pancreatic contents during TPN could be reversed by CCK but not by PBD. The hyperplastic response to CCK in orally fed rats was abolished during TPN. Devazepide did not influence the pancreatic variables in orally fed and TPN-treated rats. CONCLUSION: TPN reduces the hyperplastic response of the exocrine pancreas to CCK, and CCK reverses the hypotrophy seen during TPN. The effects of CCK on the exocrine pancreas seems to need enteral nutrition for the full expression.

Animals↗
PubMed1996

Identification of an alkaline sphingomyelinase activity in human bile.

The hydrolysis of sphingomyelin has been found to generate important signals regulating cell proliferation, differentiation and apoptosis. However, the enzymes responsible for digestion of dietary sphingomyelin have not been well documented. This study demonstrates the occurrence of a sphingomyelinase (SMase) in both human hepatic bile and gallbladder bile. The enzyme was equally found in both bacteria negative and positive bile samples and in samples obtained from patients with or without gallbladder diseases. A bacteria-free gallbladder bile was used for characterization. It was found that bile SMase hydrolyzed sphingomyelin to phosphorylcholine and ceramide with negligible activity against either phosphatidylcholine or p-nitrophenyl phosphate. The enzyme preferred an alkaline condition and the optimal pH was 9. The activity of this alkaline SMase was bile salt dependent and was fully activated by 4-6 mM bile salts. Triton X-100, the non-ionic detergent did not activate bile SMase. Ca2+ and Mg2+ ions had no significant effect at optimal bile salt concentration. The molecular mass of this enzyme was about 85 kDa as measured by Sephadex G200 gel chromatography. In conclusion, we demonstrated a SMase in bile which differs markedly from the known acid and neutral SMase. Its potential important roles in sphingomyelin digestion and gallbladder diseases require further investigation.

Alkalies↗
PubMed1996

The changes in the rat parotid glands following total parenteral nutrition and pancreatico-biliary diversion are not mediated by cholecystokinin.

CONCLUSIONS: The results of the present study suggest that the pancreas and parotid glands both respond with hypoplasia during absence of food in the digestive tract and with hyperplasia following pancreatico-biliary diversion (PBD). Factors other than cholecystokinin (CCK) are, however, involved in the effects on the parotid glands, since infusion of CCK-8S and devazepide was without influence. BACKGROUND AND AIM: Total parenteral nutrition (TPN) causes reduced pancreatic weight, whereas PBD evokes hyperCCKemia and enlargement of the rat pancreas. The pancreas and parotid glands have in part similar morphology and function. Therefore, we studied the possible presence of alterations also in the parotid glands during TPN, after PBD and during infusion of sulfated cholecystokinin (CCK-8S) and the CCK-A receptor antagonist devazepide, respectively. MATERIALS AND RESULTS: Rats either received TPN for 7 d, or were kept under otherwise identical conditions with free access to food and water. TPN markedly reduced both pancreatic and parotid wet weight and thereby also the protein and amylase contents, and pancreatic DNA content was decreased. There was a significant correlation between the pancreas and parotid glands when comparing these parameters. The concentration of plasma CCK was unaffected by TPN. PBD caused a sevenfold increase in plasma CCK and a three fold increase in the pancreatic weight compared to control rats 28 d after the operation. The protein and DNA contents in the pancreas were found to be increased. The parotid glands increased twofold in weight, but their protein and amylase contents were not affected. There was a significant correlation between the pancreas and parotid glands when comparing weight, and protein and amylase concentrations. Infusion of CCK-8S during 28 d caused a marked increase in pancreatic wet wt and protein and DNA contents. The CCK-A receptor antagonist devazepide induced a reduction in protein and DNA contents in the pancreas. The parotid glands were not affected by either treatment. No effect on the labeling index of serous and ductal cells of the parotid gland was seen at 36 h, 3, 7, and 28 d of infusion with CCK-8S or devazepide.

Amylases↗
PubMed1996

Cholecystokinin increases small intestinal motility and reduces enteric bacterial overgrowth and translocation in rats with surgically induced acute liver failure.

Enteric bacterial translocation into extraintestinal sites has been proposed as a potential route for bacterial infection in acute liver failure. Bacterial overgrowth in the intestine plays an important role in the etiology of bacterial translocation from the gut. The aim of the present study was to evaluate the influence of exogenous cholecystokinin (CCK) on intestinal transit time, enteric bacterial overgrowth and translocation in experimental acute liver failure induced by 90% hepatectomy. A delayed intestinal transit time was noted in animals subjected by subtotal hepatectomy after 1 h, followed by enteric bacterial overgrowth and translocation into the systemic circulation, mesenteric lymph nodes, and systemic organs at 2 and 4 h. Intravenous infusion of CCK stimulated intestinal transit time in animals with sham operation and subtotal hepatectomy, though a restoration to sham levels could not be obtained in the later. Moreover, enteric bacterial overgrowth and translocation were prevented in hepatectomized animals. The present data imply that impaired intestinal motility, followed by enteric bacterial overgrowth and translocation in experimental acute liver failure, could be prevented by CCK infusion.

Animals↗
PubMed1995

Time-course of the pancreatic changes following long-term stimulation or inhibition of the CCK-A receptor.

Cholecystokinin (CCK) reportedly induces both hyperplastic and hypertrophic changes in the pancreas. Blockade of the CCK receptor results in decreased pancreatic secretion and atrophy. The aim of this study was to evaluate the time-course of the effects of stimulation and inhibition of the CCK-A receptor in the rat exocrine pancreas. Male rats had infusion of sulfated CCK-8, the CCK-A receptor antagonist devazepide, or sodium chloride by osmotic minipumps. After 36 h, 3, 7, or 28 d the rats had ip injections of thymidine, and 1 h later they were sacrificed. The pancreas was excised, weighed, and its content of protein, DNA, water, and enzymes was analyzed. Histologic samples were prepared for autoradiography. Pancreatic weight, protein, and DNA were increased at 36 h after the start of CCK infusion and throughout the study period. CCK stimulation also increased the content of trypsin at days 3 and 28. The labeling index of pancreatic acinar cells was increased at 36 h. Blockade of endogenous CCK by the receptor antagonist devazepide led to decreased pancreatic weight from the third day of infusion, whereas the protein content was decreased from the seventh day. At day 28, the DNA content was decreased by devazepide. However, the labeling index of acinar cells decreased transiently already at 36 h. Neither CCK nor devazepide caused any changes of protein content:DNA content ratio during the study. Continuous infusion of CCK caused pancreatic hyperplasia already after 36 h. Stimulation up to 28 d did not cause any further effects. The adverse changes found after blockade of the CCK-A receptor showed much of the same time-course.

Animals↗
PubMed1995

The ratio between anionic and cationic trypsin in rat pancreas varies with CCK stimulation.

The effects of long-term hyperstimulation with cholecystokinin (CCK) on the pancreatic contents of anionic and cationic trypsin(ogen) and amylase were studied in the rat. Endogenous hyperCCKemia was evoked in rats by pancreaticobiliary diversion (PBD), and exogenous hyperCCKemia by continuous subcutaneous CCK infusion. In addition, the effect of continuous subcutaneous infusion of the CCK A receptor antagonist devazepide was studied. After 4 weeks blood samples were obtained for the determination of plasma CCK concentrations and the animals were sacrificed. The pancreatic glands were harvested, weighted, and extracted. The extracts were analyzed for anionic and cationic trypsin and amylase. Enzyme contents showed a large interindividual variation. The most consistent change in enzyme pattern was an increase in the ratio between anionic and cationic trypsin in animals with hyperCCKemia (PBD operated or CCK infused). Furthermore, this ratio decreased significantly in animals treated with devazepide. In conclusion, stimulation of the CCK receptor changed the ratio between anionic and cationic trypsin in the pancreatic gland, while it was reversed during blockade of the receptor.

Amylases↗
PubMed1993

The rat gastric phospholipids: increased in ulcerated mucosa and decreased after healing.

The composition and content of the gastric phospholipids were followed during development and healing of indomethacin-induced chronic, antral ulcers in rats. The individual phospholipids were identified by thin-layer chromatography and quantitatively estimated by spectrophotometric analysis of phosphate. No changes were found in phospholipid composition and content after a 24-hour fast or during the first 24 h after indomethacin was given. The total phospholipid content and the content of lysophosphatidylcholine and phosphatidylcholine were increased on the 5th day, when chronic ulcers were established. After 4 weeks, when the ulcers were healed, the total phospholipid content, and content of phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, respectively, were decreased, while the content of lysophosphatidylcholine was increased. In conclusion, the composition and content of gastric phospholipids were altered in rats with ulcers as well as in rats with healed ulcers.

Animals↗
PubMed1993

Pancreatic pain: is there a medical alternative to surgery?

The non-surgical management of chronic pancreatic pain is reviewed. In accordance with the suggested multifactorial origin of pancreatic pain, different treatment principles are practised. Besides conventional analgesic drugs, oral pancreatic enzymes seem efficient in a subgroup of patients with chronic pancreatitis. Endoscopic treatment aiming at reduction of the pancreatic duct-tissue pressure is promising, but it is still in its infancy. Coeliac nerve blockage is recommended in patients with pancreatic cancer and pain, whereas external radiotherapy plays a role in a diminishing number of these patients. Treatment of chronic pancreatic pain is an example of a complex clinical problem in which a multidisciplinary approach is mandatory.

Abdominal Pain↗
PubMed1993

Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible?

Total gastrectomy or resection of the acid-producing part of the stomach (fundectomy) in the rat induced a marked and rapid reduction in bone wet weight, ash weight, and density (expressed as ash weight in mg/mm3 bone). Bone volumes were also affected but not as much. The radius, sternum, tibia, and femur were studied. Three weeks after gastrectomy the bone ash weight was reduced by almost 30% and the density by more than 25%. Maximum bone loss (approximately 40%) occurred about 6 weeks after the operation. The bone loss after gastrectomy was somewhat greater than that after fundectomy, whereas antrectomy had a marginal effect only. The percentage trabecular bone volume, calculated from morphometric analysis of histologic sections of the tibia, was greatly reduced by gastrectomy (approximately 50%), somewhat less so by fundectomy, whereas antrectomy had little effect. We set out to study whether calcium malabsorption could explain the bone loss after gastrectomy. Gastric acid is thought to facilitate the intestinal absorption of ingested calcium by mobilizing calcium from insoluble complexes in the diet. The possibility that lack of acid might contribute to the bone loss after gastrectomy was examined in experiments in which the proton pump inhibitor omeprazole was given for 4-8 weeks at such a dose (400 mumol/kg/day) that acid secretion was blocked almost completely during the period of study. This treatment was without effect on bone. However, the possibility could not be excluded that gastrectomized rats develop calcium deficiency for some reason other than lack of acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗