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Biomedical subjects

O Olsen

Publications and source records attributed to O Olsen.

At least 91 records · Page 5Linked to original sources

Relative importance of pancreatic, hepatic, and mucosal bicarbonate in duodenal neutralization of acid in anaesthetized pigs.

Pancreatic and hepatic bicarbonate secretion and the disappearance rate of acid during duodenal acidification were measured simultaneously in anaesthetized pigs. Perfusion of the duodenum with HCl resulted in an increase in both hepatic and pancreatic bicarbonate secretion. During all acid loads hepatic bicarbonate secretion was significantly greater than pancreatic secretion. Furthermore, the disappearance rate of acid in the duodenum during diversion of both bile and pancreatic juice was significantly greater than the amount of acid which could be neutralized by the concomitant pancreatic bicarbonate secretion. Diversion of pancreatic juice from the duodenum did not affect the disappearance rate of acid at any acid load, whereas diversion of bile caused a significant decrease. Thus, in the anaesthetized pig the liver and the duodenal mucosa are of greater importance than the pancreas for the neutralization of acid in the duodenum. It is suggested that the importance of the pancreatic contribution to duodenal neutralization should be reevaluated in other species, including man.

Animals↗

The effects of omeprazole on interdigestive motility and early postprandial levels of gastrin and secretin.

Ten healthy men participated in a crossover study, and the experiments took place after 10 days of treatment (40 mg omeprazole every morning). Blood samples were drawn at fixed intervals during a complete migrating motor complex (MMC) cycle. The manometric pressure tube was removed after passage of the second duodenal phase III, and an omelet (1400 KJ) tagged with 99mTc was ingested, followed by 150 ml of water tagged with 111In-diethylenetriaminepentaacetic acid. Mean plasma gastrin (pmol/l) in phases I, II, and III in the omeprazole group was 18.8, 23.3, 19.9, respectively. The corresponding figures for the placebo group were 9.3, 9.6, 9.5, respectively. All mean values for the omeprazole group were significantly higher (p less than 0.01). Mean plasma gastrin in the omeprazole group was significantly higher in phase II than in phase I (p less than 0.05). Mean plasma secretin (pmol/l) in phases I, II, and III in the omeprazole group was 1.6, 1.4, 1.1, respectively. The corresponding figures for the placebo group were 2.0, 1.7, 2.2, respectively. Mean plasma secretin in the omeprazole group was significantly lower in phases I and III (p less than 0.05). The mean incremental integrated postprandial gastrin response (pmol.30 min/l) was significantly higher in the omeprazole group (475.0 versus 97.5) (p less than 0.05). The immediate postprandial mean value of secretin was significantly lower in the omeprazole group (p less than 0.05). We conclude that 40 mg omeprazole elicits i) a phase-related increase in fasting plasma gastrin, ii) a decrease in secretin in phases I and III, iii) an augmented meal-stimulated gastrin response, and iv) a secretin response characterized by a significantly lower mean in the immediate postprandial period.

Adult↗

Hybrid Bacillus (1-3,1-4)-beta-glucanases: engineering thermostable enzymes by construction of hybrid genes.

Hybrid (1-3,1-4)-beta-glucanase genes were constructed by extension of overlapping segments of the (1-3,1-4)-beta-glucanase genes from Bacillus amyloliquefaciens and B. macerans generated by the polymerase chain reaction (PCR). Four hybrid genes were expressed in Escherichia coli cells. The mature hybrid enzymes contain a 16, 36, 78, or 152 amino acid N-terminal sequence derived from B. amyloliquefaciens (1-3,1-4)-beta-glucanase followed by a C-terminal segment derived from B. macerans (1-3,1-4)-beta-glucanase. Biochemical characterization of parental and hybrid enzymes shows a significant increase in thermostability of three of the hybrid enzymes when exposed to an acidic environment thus combining two important enzyme characteristics within the same molecule. At pH 4.1, 85%-95% of the initial activity was retained after 1 h at 65 degrees C in contrast to 5% and 0% for the parental enzymes from B. amyloliquefaciens and B. macerans. After 60 min incubation at 70 degrees C, pH 6.0, the parental enzymes retained 5% or less of the initial activity whilst one of the hybrids still exhibited 90% of the initial activity. Of the parental enzymes B. macerans (1-3,1-4)-beta-glucanase had the lower specific activity while the hybrid enzymes exhibited specific activities that were 1.5- to 3-fold higher. These experimental results demonstrate that exchange of homologous gene segments from different species may be a useful technique for obtaining new and improved versions of biologically active proteins.

Amino Acid Sequence↗

Age and the operationalization of social support.

In most studies social network is operationalized without any consideration of age. But it is to be expected that both the prevalence and the impact on health of the various sources of social support change through life. If this is true, then the use of a global index may lead to distorted results regarding age changes of the social network. In a cross-sectional study of 1500 occupationally active, Danish men aged 16-74, the hypothesized age dependencies were studied with health operationalized as psychological well-being and social support divided into support from wife, children, family and friends. The prevalence of support from the wife increased with age, whereas her impact on health was only significantly positive in the age range 30-49. Support from family and friends was most prevalent among the youngest, but it had a positive impact on health both among the young and the old. The results regarding impact on health are corroborated by two other studies on mortality. These findings point to methodological errors that may distort results when global network measures are used irrespective of the ages of the participants studied.

Adolescent↗

Impact of work environment on cardiovascular diseases in Denmark.

STUDY OBJECTIVE: The aim was to estimate the quantitative impact of working conditions on cardiovascular diseases in Denmark. DESIGN: The study was based on a review of recent epidemiological research publications in which relative risks were estimated and risk factor prevalences were determined. The impact of working conditions was quantified by means of aetiological fractions. SETTING: The aetiological fractions were estimated on the Danish population. MAIN RESULTS: 16% of the premature cardiovascular mortality in men and 22% in occupationally active women is avoidable through interventions in the work environment. If "sedentary" work is included in the occupational risk factors, the aetiological fractions reach 51% for men and 55% for women. Taken separately, the major aetiological fractions for cardiovascular risk factors at work are respectively (women in parentheses) 6% (14%) for monotonous high paced work, 7% (7%) for shift work, and 2% (2%) for passive smoking. CONCLUSIONS: The aetiological fractions show that working conditions play a considerable role in cardiovascular diseases. Furthermore they might widen the focus of preventive cardiology from interventions directed only at individual and lifestyle risk factors to interventions directed also at working conditions.

Adolescent↗

Job strain and cardiovascular risk factors: a cross sectional study of employed Danish men and women.

As part of the World Health Organisation initiated MONICA project, 2000 men and women aged 30, 40, 50, and 60 from the general population were invited to undergo a medical examination with special emphasis on cardiovascular disease. A total of 1504 (75%) participated, 1209 of whom were employed. The participants answered a questionnaire on working, social, and health conditions and underwent clinical examinations that included the measurement of blood pressure and serum cholesterol, triglyceride, high density lipoprotein, fibrinogen, and glycated haemoglobin (HbA1C) concentrations. Using the demand-control model for measuring job strain suggested by Karasek, the employed people were classified according to those who had suffered job strain and those who had not in two different ways. The subjective classification was based on the participants' statements regarding demand and control in their jobs whereas the objective classification was based on job title and mode of payment. More women than men were classified as having high strain jobs. After adjusting for age and sex no significant association was found between coronary risk factors and subjective job strain. A tendency for an association between fibrinogen and job strain was found. Body mass index and HbA1C concentration were significantly associated with objective job strain independent of confounders.

Adult↗

Pancreatic, hepatic, and duodenal mucosal bicarbonate secretion during infusion of secretin and cholecystokinin. Evidence of the importance of hepatic bicarbonate in the neutralization of acid in the duodenum of anaesthetized pigs.

The effect of infusion of secretin alone or in combination with cholecystokinin (CCK) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion was studied in anaesthetized pigs. After laparotomy, catheters were inserted into the common bile duct, the pancreatic duct, and both ends of the duodenum. Pancreatic, hepatic, and duodenal mucosal secretions were collected during intraportal infusion of increasing doses of secretin, either alone or in combination with CCK. During infusion of secretin in doses that caused physiologic increases in plasma secretin concentrations the liver produced significantly more bicarbonate than the pancreas. A physiologic dose of CCK augmented the effect of secretin on both hepatic and pancreatic bicarbonate secretion, but the hepatic production of bicarbonate was still larger than the pancreatic production. Neither secretin alone nor secretin combined with CCK caused any changes in duodenal mucosal bicarbonate secretion. These results suggest that the liver plays an important role in the neutralization of acid in the duodenum.

Animals↗

Inhibition of cholecystokinin-stimulated pancreaticobiliary output in man by the cholecystokinin receptor antagonist MK-329.

MK-329 (formerly L-364,718) is a new nonpeptide antagonist for the peripheral (type-A) cholecystokinin (CCK) receptor, which has proved effective in blocking the actions of both exogenous and endogenous CCK in several species. To evaluate the effect of MK-329 on CCK-stimulated pancreaticobiliary output in man, six normal subjects received 10 mg MK-329 or placebo orally in a randomized, crossover fashion, before a background intravenous infusion of secretin (5 pmol/kg/h) and two doses of CCK-8 (approximately 15 and 40 pmol/kg/h, each for 1 h). Gastric and duodenal juice were aspirated separately via two double-lumen tubes, with 51Cr-ethylene-diaminetetraacetic acid as a duodenal marker. After placebo treatment the background infusion of secretin produced maximum plasma concentrations of secretin similar to postprandial values, averaging about 5 pM. After placebo treatment the low dose CCK-8 infusion (15 pmol/kg/h) increased circulating CCK concentrations from basal levels of 1.8 +/- 0.2 pM to levels similar to those observed postprandially, averaging 9.2 +/- 1.3 pM, and the high dose of CCK-8 (40 pmol/kg/h) induced supraphysiologic levels of CCK, averaging 23.4 +/- 3.2 pM. Plasma concentrations of secretin and CCK were not significantly different during MK-329 treatment. As expected, infusion of CCK-8 at both doses stimulated pancreatic exocrine secretion and gallbladder contraction in placebo controls, as indicated by increases in the output of trypsin, amylase, bicarbonate, and bilirubin. Whereas MK-329 did not significantly reduce basal pancreatic secretion, the integrated incremental output of trypsin, amylase, and bicarbonate in response to stimulation with the low (physiologic) CCK dose was inhibited by 74% (p less than 0.01), 89% (NS), and 75% (p less than 0.05), respectively. Basal bilirubin output was virtually abolished after treatment with MK-329, and the response to the low dose of CCK was reduced by 98% (p less than 0.01), indicating almost complete inhibition of gallbladder contraction at physiologic circulating concentrations of CCK. It is concluded that MK-329 is an orally active antagonist of CCK-stimulated pancreaticobiliary output in man and could thus be utilized to explore the physiologic regulation of the exocrine pancreas and gallbladder by CCK.

Adult↗

Mitochondrial malate dehydrogenase from watermelon: sequence of cDNA clones and primary structure of the higher-plant precursor protein.

The isolation and sequence of a cDNA clone encoding the complete mitochondrial malate dehydrogenase (mMDH) of watermelon cotyledons is presented. Taking advantage of the polymerase chain reaction technology partial cDNA clones from the central part, the 3' part and the 5' part of the mRNA were obtained with oligonucleotides based on directly determined amino acid sequences. Subsequently, two complete cDNA clones for mMDH were synthesized with a sense primer corresponding to the nucleotide sequence of the amino terminal end of pre-mMDH and two antisense primers corresponding to the major alternative adenylation sites found in the mRNA. The amino acid residues for substrate and cofactor binding identified by X-ray crystallography for pig heart cytoplasmic MDH are conserved in the 320 amino acid long mature higher-plant mMDH. A presequence of 27 amino acids is present at the amino terminal end of the precursor protein.

Amino Acid Sequence↗

Cholecystokinin, secretin, pancreatic polypeptide in relation to gallbladder dynamics and gastrointestinal interdigestive motility.

Using a combined technique of hepatobiliary scintigraphy and gastrointestinal motility recordings, the changes in blood concentrations of cholecystokinin (CCK), secretin and pancreatic polypeptide (PP) were studied in relation to gastrointestinal motility and gallbladder dynamics in the interdigestive state in 7 healthy male volunteers. No changes in CCK concentration were found in relation to the migrating motor complex (MMC). In 3 subjects a slightly but insignificant elevated secretin level was seen during phase I of the MMC, otherwise no changes were observed. More pronounced fluctuations in PP appeared with significantly higher values during phase III compared to phase II. Values of concentrations of CCK, secretin and PP in periods with gallbladder filling were not significantly different from the values in periods of emptying.

Adult↗

Duodenal disappearance rate of acid during inhibition of mucosal bicarbonate secretion.

In order to investigate the relation between duodenal mucosal and pancreaticobiliary bicarbonate secretion, we have studied the effect of inhibition of mucosal bicarbonate secretion by indomethacin on the disappearance rate of acid and the concomitant plasma secretin concentrations. 10 healthy subjects were studied twice, with and without indomethacin pretreatment. By means of a double-lumen tube the duodenum was perfused with increasing amounts of acid (0, 3.0, 6.0 and 9.5 mmol/h) and the disappearance rate of acid, pH of duodenal aspirate and plasma secretin were measured. In both experiments nearly all acid, even at the highest acid load, disappeared (pH greater than 6). Inhibition of the duodenal mucosal bicarbonate secretion did not decrease the acid-neutralizing capacity of the human duodenum. In fact, the disappearance rate of acid at the highest acid load was a little greater when mucosal bicarbonate secretion had been inhibited than when not (10.3 +/- 0.5 vs. 9.2 +/- 0.2 mmol/h). The pancreaticobiliary secretion of bicarbonate, as judged by plasma secretin concentrations, increased, however, earlier when mucosal bicarbonate secretion had been inhibited than when not (3.7 vs. 3.0 pmol/l at an acid load of 6.0 mmol/h). This indicates that bicarbonate from the duodenal mucosa normally plays a role in the in lumen neutralization of acid in the human duodenum.

Adult↗

Inhibition of human gastric acid secretion by peptide YY and secretin.

In 6 healthy volunteers we investigated the effect of secretin and peptide YY (PYY) on gastric acid secretion stimulated by pentagastrin (100 ng/kg/h). Secretin (0.05 CU/kg/h) and PYY (10.0 pmol/kg/h) were given intravenously either alone or in combination. Given alone secretin and PYY inhibited gastric acid output by 25 and 21%, respectively. The combined infusion of secretin and PYY inhibited acid output by 38% indicating an additive effect. The infusion of one hormone did not influence release of the other. It is suggested that the interaction of PYY and secretin on pentagastrin-stimulated gastric acid secretion in normal man is of the additive type.

Adult↗

Postpartum symptoms. Episiotomy or tear at vaginal delivery.

The influence of episiotomy was evaluated in a quasi-randomized follow-up study. In 193 primiparas with spontaneous vaginal delivery, postpartum perineal pain and insufficiency symptoms and their duration were evaluated by means of a questionnaire, 15-24 months post partum. Information about the birth and any complications was obtained from the medical records. On comparing the 85 primiparas delivered by midwives who had a low episiotomy rate (mean 21%) versus the 61 primiparas delivered by midwives with a medium episiotomy rate (mean 34%) and the 41 delivered by midwives with a high episiotomy rate (mean 70%), no differences were found regarding postpartum perineal pain and insufficiency symptoms. Postpartum perineal pain symptoms were significantly correlated to the duration of the second stage of labor, irrespective of the episiotomy rate of the midwife in charge, or of the use of episiotomy.

Adult↗

[Etiology and prevention of disease--theory and practice].

The prevention of diseases requires that their causes are known. The article presents central epidemiological concepts which relate to causality and demonstration of causal connections. It refers these to prophylactic medicine and to the future assignment of priorities as regards research funds.

Causality↗

Processing and secretion of barley (1-3,1-4)-beta-glucanase in yeast.

DNA segments encoding signal peptides from mouse alpha-amylase, yeast acid phosphatase, and yeast invertase were fused in frame to a barley (1-3,1-4)-beta-glucanase cDNA gene and expressed in yeast cells under the control of the phosphoglycerate kinase gene promoter. Pure beta-glucanase is obtained by gel filtration of concentrated yeast cell supernatant. It was shown that the glucanase pre-protein was specifically processed and the mature protein efficiently secreted when the yeast invertase signal sequence directed secretion.

Acid Phosphatase↗

Hybrid bacillus endo-(1-3,1-4)-beta-glucanases: construction of recombinant genes and molecular properties of the gene products.

Hybrid beta-glucanase genes were constructed by the reciprocal exchange of the two halves of the isolated beta-glucanase genes from Bacillus amyloliquefaciens and B. macerans. The beta-glucanase hybrid enzyme 1 (H1) contains the 107 amino-terminal residues of mature B. amyloliquefaciens beta-glucanase and the 107 carboxyl-terminal amino acid residues of B. macerans beta-glucanase. The reciprocal beta-glucanase hybrid enzyme 2 (H2) consists of the 105 amino-terminal residues from the B. macerans enzyme and the carboxyl-terminal 107 amino acids from B. amyloliquefaciens. The biochemical properties of the two hybrid enzymes differ significantly from each other as well as from both parental beta-glucanases. Hybrid beta-glucanase H1 exhibits increased thermostability in comparison to other beta-glucanases, especially in an acidic environment. This hybrid enzyme has maximum activity between pH 5.6 and 6.6, whereas the pH-optimum for enzymatic activity of B. amyloliquefaciens beta-glucanase was found to be at pH 6 to 7 and for B. macerans at pH 6.0 to 7.5. Hybrid enzyme 1 being more heat stable than both parental enzymes represents a case of intragenic heterosis. Hybrid beta-glucanase 2 (H2) was found to be more thermolabile than the naturally occurring beta-glucanases it was derived from and the pH-optimum for enzymatic activity was determined to be between pH 7 and pH 8.

Amino Acid Sequence↗