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Biomedical subjects

B Vonen

Publications and source records attributed to B Vonen.

At least 19 recordsLinked to original sources
PubMed2007

Impact of radiotherapy on local recurrence of rectal cancer in Norway.

BACKGROUND: The purpose of this study was to analyse the impact of radiotherapy on local recurrence of rectal cancer in Norway after the national implementation of total mesorectal excision (TME). METHODS: This was a prospective national cohort study of 4113 patients undergoing major resection of rectal carcinoma between November 1993 and December 2001. RESULTS: The proportion of patients who had radiotherapy before or after operation increased from 4.6 per cent in 1994 to 23.0 per cent in 2001. The cumulative 5-year local recurrence rate decreased from 16.2 to 10.7 per cent. Multivariable analysis showed that preoperative radiotherapy significantly reduced local recurrence (hazard ratio 0.59 (95 per cent confidence interval 0.39 to 0.87)). The use of preoperative radiotherapy in patients from a local hospital offering radiotherapy was 50 per cent higher than that for patients from a hospital without such services (P = 0.003); cumulative 5-year local recurrence rates for these patients were 10.6 and 15.8 per cent respectively (P < 0.001). CONCLUSION: Following national implementation of TME for rectal cancer, increased use of preoperative radiotherapy appeared to reduce recurrence rates further.

Aged↗
PubMed2006

Improvement of real-time polymerase chain reaction for quantifying TNF-alpha mRNA expression in inflamed colorectal mucosa: an approach to optimize procedures for clinical use.

OBJECTIVE: The precise measurement of local tumor necrosis factor alpha (TNF-alpha) expression in tissue is important in understanding the pathogenesis of inflammatory bowel diseases (IBD). Real-time polymerase chain reaction (PCR) is a sensitive, versatile method and is becoming a commonly used tool for the quantification of gene expression. The aim of this study was to optimize the laboratory procedure for biopsy sampling, storage and calibration of result for TNF-alpha mRNA quantification with real-time PCR of colorectal biopsies. MATERIAL AND METHODS: Endoscopic biopsies from the colorectum were obtained from 18 patients with ulcerative colitis (UC), 11 patients with Crohn's disease (CD) and 18 normal controls. Optimization of procedures for real-time PCR performance was carried out. RESULTS: The transport medium, RNAlater, exhibited a high preservation effect against RNA degradation even after 8 days of storage at room temperature; one biopsy from each patient was sufficient for RNA extraction, cDNA synthesis and TNF-mRNA quantification. An assay was established with a technical reproducible sensitivity of 100 copies/microL. The observed interassay variations were 7.4 % coefficient of variation (CV) and 7.2 % CV in low and high TNF-alpha mRNA expression biopsies, respectively. TNF-alpha mRNA levels in colorectal biopsies from patients with either CD or moderate to severe UC were markedly increased, and 8 approximately 9-fold higher than those in healthy controls. CONCLUSIONS: This optimization improves the clinical use of real-time PCR for quantification of TNF-alpha gene expression in colorectal biopsies and provides a sensitive reproducible assay.

Adult↗
PubMed1997

Adjuvant chemotherapy (5-fluorouracil and levamisole) in Dukes' B and C colorectal carcinoma. A cost-effectiveness analysis.

BACKGROUND: Adjuvant chemotherapy (5-fluorouracil, levamisole) is now standard practice in the treatment of Dukes' B and C coloretal carcinoma (CRC), and this has increased the financial burden on health care systems world-wide. PATIENTS AND METHODS: Between 1993 and 1996, 95 patients in northern Norway were included in a national randomised CRC study, and assigned to surgery plus adjuvant chemotherapy or surgery alone. In April 1996, 94 of the patients were evaluable and 82 were still alive. The total treatment costs (hospital stay, surgery, chemotherapy, administrative and travelling costs) were calculated. A questionnaire was mailed to all survivors for assessment of the quality of their lives (QoL) (EuroQol questionnaire, a simple QoL-scale, global QoL-measure of the EORTC QLQ-C30), and 62 of them (76%) responded. RESULTS: Adjuvant chemotherapy in Dukes' B and C CRC raised the total treatment costs by 3,369 pounds. The median QoL was 0.83 (0-1 scale) in both arms. Employing a 5% discount rate and an improved survival of adjuvant therapy ranging from 5% to 15%, we calculated the cost of one gained quality-adjusted life-year (QALY) to be between 4,800 pounds and 16,800 pounds. CONCLUSION: Using a cut-off point level of 20,000 pounds per QALY, adjuvant chemotherapy in CRC appears to be cost-effective only when the improvement in 5-year survival is > or = 5%. Adjuvant chemotherapy does not affect short-term QoL.

Adult↗
PubMed1997

Effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin in humans.

Cimetidine reduces the appetite and weight in healthy overweight subjects. Gastrointestinal regulatory peptides such as cholecystokinin (CCK) have been proposed to mediate the satiety signal from gut to brain. Therefore, the effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin was studied. After an overnight fast, 12 healthy volunteers were given cimetidine (400 mg) on day 1, breakfast on day 2, and cimetidine 20 min before breakfast on day 3. Plasma concentrations of cholecystokinin and gastrin were measured by radioimmunoassay. Plasma cholecystokinin concentration increased with one major peak observed 30 min and one smaller peak observed 120 min after intake of cimetidine. The meal induced an increase in the plasma concentration of cholecystokinin, while cimetidine prior to the meal elicited a sustained postprandial cholecystokinin response. Cimetidine had no effect on the basal plasma concentration of gastrin. The meal induced an increase in the plasma concentration of gastrin, while cimetidine prior to the meal elicited a sustained postprandial gastrin response. In conclusion, cimetidine increases the basal concentration of plasma cholecystokinin and elicits a sustained postprandial response of both cholecystokinin and gastrin. At least the cholecystokinin response may be one mechanism by which cimetidine reduces the appetite.

Adolescent↗
PubMed1997

H2-receptor antagonist reduces food intake and weight gain in rats by non-gastric acid secretory mechanisms.

The H2-receptor antagonist cimetidine reduces appetite and weight in overweight healthy subjects and in overweight subjects with type II diabetes mellitus. The aim of this study was to characterize the mechanisms of this effect in rodents. Drugs were administered three times a day, 30 min before 1 h periods of free access to food. In one group of rats (n = 9), cimetidine (8 mg) treatment resulted in significantly lower cumulative food intake than in a control group (n = 9). The total intakes of food during the observation period of 22 days were 325.3 +/- 29.1 g and 346.3 +/- 16.7 g in the cimetidine and control groups, respectively. During the observation period, the weight gain in the cimetidine group was 63.3 +/- 15.8 g, which was significantly lower than the weight gain of 74.8 +/- 14.2 g in the control group, i.e. the cimetidine induced a 15.4% reduction in the weight gain during the observation period of 22 days. The weight gained per weight of food ingested was 0.20 +/- 0.04 (g/g) and 0.22 +/- 0.04 (g/g) in the cimetidine and control groups, respectively (NS). In other experiments, ranitidine (3 mg) and famotidine (0.4 mg), but not omeprazole (0.4 mg), taken three times a day for 8 days reduced the weight gain when compared with a control group (n = 7 in each group). We therefore conclude that the effects of the H2-receptor antagonists are not mediated by inhibitory mechanisms on the gastric acid secretion.

Animals↗
PubMed1996

[Laparoscopic hernia repair. A useful method for surgical treatment of inguinal hernia?].

Between September 1992 and May 1993 14 groin hernias in 13 patients were treated with laparoscopic transabdominal preperitoneal repair using a polypropylene mesh to reinforce the abdominal wall. There were two indirect and 12 direct hernias. Five hernias were recurrent. There were no perioperative complications. In the follow up period 14-24 months after the operations, two patients developed recurrent hernias after four and ten months respectively, one patient presented with a new hernia on the contralateral side, and one patient died from cardiac disease. Laparoscopic hernia repair is technically demanding and in our setting is more time- and resource consuming than an open, tension-free repair. Thus it is questionable whether this method should be used in primary hernia repair. It may, however, have a place in the treatment of recurrent hernias and bilateral hernias.

Adult↗
PubMed1996

The effect of fructose metabolism on the accumulation of inositol phosphates in rat pancreatic islets.

The mechanism by which glucose recognition of B cells results in the release of inositol 1,4,5-trisphosphate is not known at present. In pancreatic islets, fructose shares a common metabolic pathway with glucose from the second step of glycolysis and can augment insulin secretion at stimulatory glucose levels. To evaluate the impact of glycolysis on the release of inositol 1,4,5-trisphosphate, we studied the effect of glucose and fructose metabolism on insulin secretion and the activation of inositol-specific phospholipase C, using collagenase digested rat pancreatic islets incorporated with 3H-labelled myo-inositol. Inositol phosphates, generated by the cleavage of phosphatidyl inositol by inositol phospholipase C, were analyzed using fast protein liquid chromatography. The islets were exposed to 3.3, 5.5 and 12 mmol 1(-1) glucose for 45 min in the absence or presence of 10, 20 or 30 mmol 1(-1) fructose, and the amount of insulin released into the medium was measured. Intracellular inositol phosphate accumulation was measured under the same glucose concentrations with 0, 10 and 30 mmol 1(-1) fructose. As expected, fructose alone had no insulinotropic effect, but potentiated the glucose-induced (5.5 and 12 mmol 1(-1)) insulin secretion at concentrations of 10-30 mmol 1(-1). Glucose (12 vs. 3.3 mmol 1(-1)) significantly increased both intracellular content of inositol 1,4,5-trisphosphate, as well as its metabolite inositol 1,3,4-trisphosphate. Fructose, however, had no potentiating effects on the accumulation of inositol phosphates. It is therefore supposed that glucose does not activate inositol-specific phospholipase C via the glycolysis. Further, since fructose did not activate inositol-specific phospholipase C, this stimulation is likely to be induced by glucose as such.

Animals↗
PubMed1993

Phosphoinositide metabolism in a polyoma-BK-virus-transformed pancreatic islet cell line: evidence for constitutively activated phospholipase C.

We have characterized the phosphoinositide metabolism in a polyoma-BK-virus-transformed rat pancreatic islet cell line which has highly malignant characteristics, expresses viral T-antigen and has lost insulin-secreting capacity. After incorporation with [3H]inositol to isotopic equilibrium, all inositol metabolites were analyzed. When compared with normal pancreatic islets, increased levels of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3), inositol 1,3,4-trisphosphates and inositol tetrakisphosphate (Ins-P4), and decreased levels of phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP2) were found. The Ins-1,4,5-P3/PIP2 ratio increased, whereas the PIP2/PIP ratio was not altered after the transformation. In the pancreatic islet cell line there was a stable accumulation of inositol phosphates at 3.3 mM glucose. Glucose, KCl, cholecystokinin (CCK) and carbachol with and without LiCl were all without effect on the accumulation of inositol phosphates. Somatostatin inhibited the accumulation of inositol phosphates but a Ca(2+)-free/EDTA solution did not. Preincubation with cholera toxin or pertussis toxin inhibited the accumulation of inositol phosphates at 3.3 mM glucose except for Ins-P4, whereas no effect was observed on the phosphoinositides. NaF stimulated the accumulation of inositol phosphates, with a concomitant decrease in the phosphoinositides, whereas neomycin was without effect on the inositol phosphates. In normal pancreatic islets, pertussis toxin inhibited the CCK-induced increase in Ins-1,4,5-P3, whereas no effect was seen at 3.3 mM glucose. Finally, pertussis toxin inhibited the CCK-induced increase in the Ins-1,4,5-P3/PIP2 ratio in normal pancreatic islets. The same inhibition was also found in the pancreatic islet cell line at 3.3 mM glucose. We conclude that in the transformed pancreatic islet cell line the phosphoinositide hydrolysis is constitutively activated at the level of phospholipase C, with a substantial loss of regulatory control.

3T3 Cells↗
PubMed1993

Cholecystokinin and somatostatin modulate the glucose-induced insulin secretion by different mechanisms in pancreatic islets. A study on phospholipase C activity and calcium requirement.

To study the interaction between the phospholipase C activation and the insulin secretion, isolated pancreatic islets were stimulated with glucose and the sulfated cholecystokinin octapeptide (CCK). To discriminate between intracellular mechanisms, experiments with agents inhibiting adenylyl cyclase and calcium-channels like somatostatin and verapamil, were performed. The phospholipase C activity, i.e. the accumulation of inositol phosphates, was increased by CCK (100 nmol l-1) at 3.3 mmol l-1 glucose. This effect of CCK did not require extracellular Ca2+, was not inhibited by somatostatin (100 nmol l-1), and no concomitant increase in the insulin secretion was observed. Both the phospholipase C activity and the insulin secretion increased in response to 12 mmol l-1 glucose. Somatostatin was able in some extent to inhibit these effects of glucose. At 12 mmol l-1 glucose, the phospholipase C activity and the insulin secretion were potentiated by CCK. CCK also counteracted the effect of somatostatin on the phospholipase C activity and the insulin secretion. Verapamil (2.5 umol l-1) more or less completely inhibited both the glucose-induced phospholipase C activity and the insulin secretion. Moreover, whereas the CCK-induced increase in the phospholipase C activity was unaffected, verapamil blocked the CCK-induced increase in the insulin secretion. We conclude that CCK directly activates phospholipase C, whereas glucose and somatostatin modulates phospholipase C via a Ca(2+)-dependent mechanism. CCK potentiates the insulin secretion by increased phospholipase C activity, but with a requirement of glucose at an apparent threshold level of Ca(2+)-influx.

Animals↗
PubMed1992

Transformed rat pancreatic islet-cell lines established by BK virus infection in vitro.

Single-cell suspensions of primary rat pancreatic islet cells were infected with BK virus (BKV) prototype (Gardner) and the naturally occurring BKV strain (TU), isolated from human urine. These viral strains have different sequences in their non-coding control regions which contain promoter-enhancer elements and origin of DNA replication. Uninfected cell cultures disintegrated within 3 weeks, while a varying number of virus-infected cultures were immortalized and a majority exhibited focal areas of 2-dimensional growth. A significantly higher proportion of the BKV (TU)- than of the BKV (Gardner)-infected cultures were immortalized. Large tumor (T) antigen expression was evident in virus-infected cultures from day 4 post infection (p.i.), while insulin secretion decreased steadily during the first weeks of culture. Two cell lines were established from BKV (TU)-infected cultures. Line 5A4 was contact-inhibited, growing as a dense monolayer, while 6A3 demonstrated foci of 2-dimensional growth. Both cell lines have retained their morphology and T-antigen expression for approximately 130 passages. At high passages a low level of intracellular insulin, but no secretion into media, was detected. Based on standard biological tests (reduced serum requirements, growth at low cell density, anchorage-independent growth and tumor induction in nude mice) both cell lines have a fully transformed phenotype, but 6A3 appears to be more malignantly transformed. Since both cell lines were established simultaneously from the same primary cells with the same virus batch, they provide an opportunity to study the transforming mechanisms of BKV in a relative context.

Animals↗
PubMed1992

Sorbitol in isolation of rat pancreatic islets. Effects on islet yield, insulin secretion and accumulation of inositol phosphates.

Tissue aggregation and exocrine contamination are problems encountered in gradient separation of pancreatic islets. Here we report that sorbitol used as an osmotic component in Percoll gradients gives a low ionic strength gradient with improved purity of islet fraction, less islet aggregation and reduced time for final manual rinsing following separation in gradients with NaCl as osmotic component. Previous reports have indicated that long-term (weeks) exposure to high sorbitol concentrations leads to low intracellular levels of inositol phosphates and subsequent effects on the intracellular signal transduction in cells. In our model, short-term exposure to high sorbitol concentrations had no effect on the accumulation of the inositol phosphates or insulin secretion caused by glucose. On the other hand, sorbitol increased the basal insulin secretion three-fold, apparently via a non-stimulatory mechanism. Therefore, we conclude that sorbitol is preferable to NaCl as the osmotic component in Percoll gradient separation of rat pancreatic islets, although long-term exposure should be avoided due to potential toxic effects.

Animals↗
PubMed1992

Glucagon mediates arginine-induced somatostatin secretion from isolated rat pancreatic islets.

Glucagon has been suggested to be a mediator of intra-islet paracrine effect of insulin and somatostatin during nutritive stimulation. The aim of this study was to reveal possible intra-islet interactions between insulin, somatostatin and glucagon in a batch stimulation model with isolated pancreatic islets. Such interactions may influence stimulus-secretion experiments in this experimental model. In our hands arginine stimulated somatostatin secretion only in the presence of insulin antiserum. Furthermore, arginine-induced glucagon secretion was greatly increased following addition of insulin antiserum. The addition of glucagon antiserum inhibited these effects of insulin antiserum on somatostatin secretion. In conclusion, glucagon apparently represents the central mediator of arginine effects on somatostatin secretion in isolated rat pancreatic islets in batch stimulation experiments.

Animals↗
PubMed1991

[Use of personal computers for statistical analyses].

We report the range in elapsed time for various statistical analyses and for the same logistic regression analysis in 23 different personal computers (PCs). Without a floating-point coprocessor, the elapsed time increased from ten to 113 minutes in the same PC. Elapsed time ranged from two to 45 minutes from 80486 to 8086 PCs with a floating-point coprocessor. The PC equipment we need strongly depends on the type and frequency of the statistical analyses we are to perform. If a floating-point coprocessor is installed, the 80286/80287 PC family may be fast enough for most users.

Microcomputers↗
PubMed1991

The interaction between cAMP-dependent and cAMP-independent mechanisms in mediating the somatostatin inhibition of insulin secretion in isolated rat pancreatic islets.

To characterize the intracellular mechanisms by which somatostatin modulates the insulin secretion, studies were performed with isolated rat pancreatic islets at 12 mmol l-1 glucose. Somatostatin (0.1-1000 nmol l-1) inhibited the glucose-induced insulin secretion concentration-dependently. Increasing intracellular cAMP concentration either with dibutyryl-cAMP (1 mmol l-1) or by the adenylate cyclase activator forskolin (20 mumol l-1) partly reversed the inhibition by somatostatin (100 nmol l-1). Neither somatostatin (100 nmol l-1) nor dibutyryl-cAMP (1 mmol l-1 were able to affect the low insulin secretion observed in the absence of extracellular Ca2+. To study cAMP-independent mechanisms of somatostatin, the experiments were performed with and without dibutyryl-cAMP (1 mmol l-1) present. Both somatostatin (100 nmol l-1) and the Ca(2+)-channel blocker verapamil (25 mumol l-1) inhibited the insulin secretion both with and without dibutyryl-cAMP present. An additional inhibition of the insulin secretion was observed when somatostatin was combined with verapamil in the absence, but not in the presence of dibutyryl-cAMP. We conclude that somatostatin inhibits the glucose-induced insulin secretion both by cAMP-dependent mechanism which requires extracellular Ca2+, and by cAMP-independent/verapamil-sensitive Ca(2+)-channel-dependent mechanism.

Animals↗
PubMed1991

Somatostatin inhibition of phospholipase C activity in isolated rat pancreatic islets.

We have assessed the effect of somatostatin on the phospholipase C activity in isolated rat pancreatic islets. The phospholipase C activity was measured as the generation of inositol 1,4,5-trisphosphate and its metabolite inositol 1,3,4-trisphosphate from the hydrolysis of polyphosphoinositides. Inositol phosphates were measured using anion-exchange fast protein liquid chromatography analysis of extracts from islets prelabelled with myo-[3H]inositol. Somatostatin (1-1000 nmol l-1) significantly inhibited the glucose-induced (12 mmol l-1) phospholipase C activity in a concentration-dependent manner. The Ca2+ channel blocker verapamil (25 mumol l-1) also inhibited the glucose-induced (12 mmol l-1) phospholipase C, whereas the combination of somatostatin and verapamil did not induce any additional inhibition. At 3.3 mmol l-1 glucose, the hypoglycaemic sulphonylurea, tolbutamide (1 mmol l-1), increased the phospholipase C activity. This effect was reversed by somatostatin (100 nmol l-1). Tolbutamide did not further increase the glucose-induced (12 mmol l-1) phospholipase C activity. However, the somatostatin inhibition of glucose-induced (12 mmol l-1) phospholipase C was reversed by tolbutamide. The activator of adenylyl cyclase, forskolin (20 mumol l-1), did not exert any effect on the PLC-inhibition of somatostatin, whereas forskolin alone inhibited the phospholipase C activation at 12 mmol l-1 glucose. Our study demonstrates that somatostatin inhibits the hydrolysis of polyphosphoinositides in pancreatic islets, apparently via a mechanism dependent on Ca2+ and not on cAMP.

Animals↗
PubMed1989

Effect of cholecystokinin on the accumulation of inositol phosphates in isolated pancreatic islets.

Sulfated cholecystokinin octapeptide (CCK-8S) potentiated glucose-induced secretion in isolated pancreatic islets with a maximal effect at 12 mM glucose, whereas no effect was observed at 3.3 and 25 mM glucose. This effect of CCK-8S was maximal at 10(-7) M. Anion-exchange fast-protein liquid chromatography analysis of [3H]inositol phosphates derived from islets prelabeled with myo-[3H]inositol showed that glucose induced accumulation of the 1,4,5-isomer of inositol trisphosphate and of inositol tetrakisphosphate. At 3.3 mM glucose, CCK-8S stimulated accumulation of inositol trisphosphate and inositol tetrakisphosphate to levels induced by 25 mM glucose alone. The net effect of CCK-8S on the accumulation of the inositol phosphates was maximal at 12 mM glucose and decreased at higher glucose concentrations. At 12 mM glucose the accumulation of inositol phosphates increased gradually up to 10(-7) M CCK-8S. This study indicates that CCK-8S potentiates glucose-induced insulin secretion through a mechanism involving the hydrolysis of polyphosphoinositides and the generation of inositol phosphates. However, activation of the inositol cycle per se did not seem to induce insulin secretion.

Animals↗