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S Larsen

Publications and source records attributed to S Larsen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Rhamnogalacturonan acetylesterase elucidates the structure and function of a new family of hydrolases.

BACKGROUND: The complex polysaccharide rhamnogalacturonan constitutes a major part of the hairy region of pectin. It can have different types of carbohydrate sidechains attached to the rhamnose residues in the backbone of alternating rhamnose and galacturonic acid residues; the galacturonic acid residues can be methylated or acetylated. Aspergillus aculeatus produces enzymes that are able to perform a synergistic degradation of rhamnogalacturonan. The deacetylation of the backbone by rhamnogalacturonan acetylesterase (RGAE) is an essential prerequisite for the subsequent action of the enzymes that cleave the glycosidic bonds. RESULTS: The structure of RGAE has been determined at 1.55 A resolution. RGAE folds into an alpha/beta/alpha structure. The active site of RGAE is an open cleft containing a serine-histidine-aspartic acid catalytic triad. The position of the three residues relative to the central parallel beta sheet and the lack of the nucleophilic elbow motif found in structures possessing the alpha/beta hydrolase fold show that RGAE does not belong to the alpha/beta hydrolase family. CONCLUSIONS: Structural and sequence comparisons have revealed that, despite very low sequence similarities, RGAE is related to seven other proteins. They are all members of a new hydrolase family, the SGNH-hydrolase family, which includes the carbohydrate esterase family 12 as a distinct subfamily. The SGNH-hydrolase family is characterised by having four conserved blocks of residues, each with one completely conserved residue; serine, glycine, asparagine and histidine, respectively. Each of the four residues plays a role in the catalytic function.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase.

Here we report the first three-dimensional structure of a phosphoribosylpyrophosphate (PRPP) synthetase. PRPP is an essential intermediate in several biosynthetic pathways. Structures of the Bacillus subtilis PRPP synthetase in complex with analogs of the activator phosphate and the allosteric inhibitor ADP show that the functional form of the enzyme is a hexamer. The individual subunits fold into two domains, both of which resemble the type I phosphoribosyltransfereases. The active site is located between the two domains and includes residues from two subunits. Phosphate and ADP bind to the same regulatory site consisting of residues from three subunits of the hexamer. In addition to identifying residues important for binding substrates and effectors, the structures suggest a novel mode of allosteric regulation.

Adenosine Diphosphate↗
PubMed2000

Molecular aspects of beta-ketoacyl synthase (KAS) catalysis.

Crystal structure data for Escherichia coli beta-ketoacyl synthase (KAS) I with C(10) and C(12) fatty acid substrates bound in conjunction with results from mutagenizing residues in the active site leads to a model for catalysis. Differences from and similarities to the other Claisen enzymes carrying out decarboxylations reveal two catalytic mechanisms, one for KAS I and KAS II, the other for KAS III and chalcone synthase. A comparison of the structures of KAS I and KAS II does not reveal the basis of chain-length specificity. The structures of the Arabidopsis thaliana KAS family are compared.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed2000

Characterization and crystallization of an active N-terminally truncated form of the Escherichia coli glycogen branching enzyme.

The prokaryotic glycogen branching enzymes (GBE) can be divided into two groups on the basis of their primary structures: the first group of enzymes, which includes GBE from Escherichia coli, is characterized by a long N-terminal extension that is absent in the enzymes of the second group. The extension consists of approximately 100 amino-acid residues with unknown function. In order to characterize the function of this region, the 728 amino-acid residue, full-length E. coli GBE, and a truncated form (nGBE) missing the first 107 amino-acid residues were overexpressed in E. coli. Both enzymes were purified to homogeneity by a simple purification procedure involving ammonium sulphate precipitation, ion-exchange chromatography, and a second ammonium sulphate precipitation. Purified full-length enzyme was poorly soluble and formed aggregates, which were inactive, at concentrations above 1 mg.mL-1. In contrast, the truncated form could be concentrated to 6 mg.mL-1 without any visible signs of aggregation or loss of activity on concentration. The ability to overexpress nGBE in a highly soluble form has allowed us to produce diffracting crystals of a branching enzyme for the first time. A comparison of the specific activities of purified GBE and nGBE in assays where amylose was used as substrate demonstrated that nGBE retained approximately half of the branching activity of full-length GBE and is therefore a suitable model for the study of the enzymes' catalytic mechanism.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2000

Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy.

BACKGROUND: The causes of albuminuria in patients with type 2 diabetes are heterogeneous and are scantily investigated, particularly if the patient has a lack of diabetic retinopathy. Therefore, we evaluated the structural background of albuminuria in a large consecutive group of Caucasian patients with type 2 diabetes without retinopathy. METHODS: Three hundred forty-seven consecutive patients with type 2 diabetes with persistent albuminuria (>300 mg/24 h) were recorded. Fundus photo (80%) and ophthalmoscopy were performed. Ninety-three (27%) had no retinopathy, and a kidney biopsy was performed in 52 (56%) of these patients. An insufficient tissue sample was obtained in one patient. The biopsies were evaluated by three masked nephropathologists. RESULTS: The biopsies revealed diabetic glomerulopathy in 69% of the patients (28 males and 7 females), while the remaining 31% (95% CI, 18 to 44) had either nondiabetic glomerulopathies such as glomerulonephritis (N = 7, 6 males and 1 female, 13%) or normal glomerular structure (N = 9, 7 males and 2 females, 18%). No significant differences in sex, age (56 +/- 8 vs. 53 +/- 10 years, mean SD), body mass index (30 +/- 4 vs. 31 +/- 8 kg/m2), known duration of diabetes (6 +/- 6 vs. 4 +/- 3 years), GFR (95 +/- 29 vs. 89 +/- 31 mL/min/1.73 m2), albuminuria (1304 +/- 169 to 4731 vs. 1050 +/- 181 to 5176 mg/24 hours), blood pressure (150/87 +/- 16/9 vs. 145/89 +/- 16/9 mm Hg), prevalence of hypertension (89 vs. 100%), hemoglobin A1c (8.2 +/- 1.6% vs. 9.0 +/- 2.5%), and serum total cholesterol (7.1 +/- 2.4 vs. 6.3 +/- 1.6 mmol/L) were found between patients with and without diabetic glomerulopathy. CONCLUSIONS: Albuminuric patients with type 2 diabetes without diabetic retinopathy have a prevalence of biopsies with normal glomerular structure or nondiabetic kidney diseases of approximately 30%. A separation between diabetic and nondiabetic glomerular lesions was not possible based on demographic, clinical, or laboratory data. Consequently, such patients may require further evaluation, including a kidney biopsy.

Adult↗
PubMed2000

Cephalic phase of lipolysis is impaired in pancreatic insufficiency: role of gastric lipase.

BACKGROUND: Gastric lipase contributes significantly to overall lipolysis and is regulated by interacting neuro-hormonal mechanisms. Patients with alcoholic chronic pancreatitis (ACP) have low, or even absent, activity of pancreatic lipases. In that state the secretion of gastric lipase could be essential and compensate for the pancreatic defect. However, conflicting studies have not resolved the order of magnitude of gastric lipase secretion in these patients. This could be explained by differences in regulatory mechanisms, gastric mucosal changes, and abdominal vagal tone. METHODS: Nasogastric intubation with modified sham feeding and upper endoscopy including biopsies for histologic classification and Helicobacter pylori infection status were performed in eight ACP patients, and eight healthy volunteers were studied on separate occasions. Vagal nerve function was assessed by calculation of heart rate variability in ACP patients. Gastric lipase was measured in aspirates by means of enzyme-linked immunosorbent assay and an enzyme kinetic assay. Plasma concentrations of gastrin, secretin, cholecystokinin, and pancreatic polypeptide were measured throughout the study. RESULTS: Sham feeding rapidly and significantly increased gastric lipase secretion in healthy volunteers, whereas ACP patients did not respond to sham feeding. Two of eight patients were infected with H. pylori and had mucosal changes accordingly. The lack of lipase response could not be ascribed to dysfunction of the abdominal vagus. CONCLUSIONS: The cephalic phase of gastric lipase secretion is impaired in ACP patients. Although their fundic cells continue to secrete gastric lipase, they are not subject to normal neuro-hormonal regulation.

Adult↗
PubMed2000

Effect of glucagon-like peptide 1(7-36)amide in insulin-treated patients with diabetes mellitus secondary to chronic pancreatitis.

Diabetes mellitus secondary to chronic pancreatitis is characterized by a progressive destruction of the pancreas, including loss of the islet cells, leading to a form of diabetes that can mimic both type 1 and type 2 diabetes. Glucagon-like peptide 1(7-36)amide (GLP-1), an intestinally derived insulinotropic hormone, represents a potential therapeutic agent for type 2 diabetes, because exogenous GLP-1 has been shown to increase the insulin and reduce the glucagon concentrations in these patients, and thus induce lower blood glucose, but without causing hypoglycemia. Ten patients with diabetes mellitus secondary to chronic pancreatitis and five normal subjects were studied. Nine patients were treated with insulin and one patient with sulfonylurea. In the fasting state, saline or GLP-1 in doses of 0.4 or 1.2 pmol/min/kg body weight were infused intravenously for 4 hours. Blood glucose was reduced in all patients with both doses of GLP-1; plasma C-peptide increased (p<0.02), and plasma glucagon decreased (p<0.02) compared with basal levels, also in three patients with normoglycemia and high levels of presumably exogenous insulin. Similar results were obtained in the normal subjects. In conclusion, GLP-1 treatment may be considered in patients with diabetes mellitus secondary to chronic pancreatitis, provided that a certain amount of alpha- and beta-cell secretory capacity is still present.

Aged↗
PubMed2000

Structural characterization of protonated benzeneseleninic acid, the dihydroxyselenonium ion

The structure of the dihydroxyphenylselenonium ion (C(6)H(7)O(2)Se(+)) has been determined in its benzenesulfonate (C(6)H(5)O(3)Se(-)-) and p-toluenesulfonate (C(7)H(7)O(3)S(-)) salts. Whereas the former salt is disordered, the latter less dense salt is well defined. This difference in crystallization behaviour is attributed to a C-H.O hydrogen bond involving the methyl group of the p-toluenesulfonate ion. The two salts display very similar hydrogen-bond arrangements and differ only with respect to the stacking of the phenyl groups. The dihydroxyselenonium ion is a strong acid with a pK value of -0.9 determined from the variation of the (77)Se chemical shift. A comparison with the two deprotonated species reveals a systematic increase in the Se-O bond lengths and the pyramidal configuration around Se with the number of protons attached.

Journal Article↗
PubMed2000

Crystallization and preliminary X-ray studies of membrane-associated Escherichia coli dihydroorotate dehydrogenase.

Dihydroorotate dehydrogenases (DHODs) are flavin-containing enzymes which catalyse the conversion of (S)-dihydroorotate to orotate, the fourth step in the de novo biosynthesis of pyrimidine nucleotides. Two major families of DHODs have now been identified based on their amino-acid sequence similarities. The two families differ in their reaction mechanisms, but structures are only known of enzymes belonging to family 1. DHOD from Escherichia coli is a typical member of family 2, which contains the membrane-associated enzymes from Gram-negative bacteria and eukaryotes. Yellow crystals grown of this enzyme belong to the space group P4(1)2(1)2 or P4(3)2(1)2. The unit-cell parameters are a = b = 119.2, c = 294.3 A. Owing to the rather large c axis, the currently available resolution of data is 2.2 A.

Cell Membrane↗
PubMed2000

The Maudsley Obsessional-Compulsive Inventory and OCD in a Norwegian nonclinical sample.

The 30 item Maudsley Obsessional-Compulsive Inventory (MOCI) was given to 294 under graduate students. The inventory achieved an acceptable internal consistence, but somewhat low reliability. There were no sex difference in total MOCI score, or in any of the subscales. 31% of the variance seemed to be explained by item 18: "attending too much to details", and more than 65% of the variance is explained by the checking subscale. The data give some interesting indications of the prevalence of OCD in the population.

Adult↗
PubMed2000

Bone mineral metabolism, bone mineral density, and body composition in patients with chronic pancreatitis and pancreatic exocrine insufficiency.

BACKGROUND: Calcium and vitamin D homeostasis seem to be abnormal in patients with exocrine pancreatic dysfunction resulting from cystic fibrosis. Only a few studies have evaluated and described bone mineral metabolism in patients with chronic pancreatitis and pancreatic insufficiency. METHODS: Thirty-two patients with chronic pancreatitis and residual exocrine pancreatic function (group 1) and 26 patients with pancreatic exocrine insufficiency (i.e., meal-stimulated intraduodenal lipase <10% of lowest normal range and steatorrhea) (group 2) were studied. Serum levels of total calcium, phosphate, 25 (OH)D, 1.25(OH)2D, alkaline phosphatase, and parathyroid hormone were measured. Bone mineral density (BMD), bone mineral content (BMC), lean body mass (LBM), and fat mass (FM) were measured using a dual-energy X-ray absorptiometry (DXA) scanner. RESULTS: Alcohol was a causative factor in 79% of the patients. Fifty-six percent in group 1 and 69% in group 2 had Z-scores of the BMD < -1. The mean Z-score was -1.16 +/- 1.29 in group 1 and -1.32 +/- 0.90 in group 2. The mean Z-score of the BMC was -1.02 +/- 1.17 vs -1.39 +/- 0.987. In both groups mean 25 (OH)D and mean 1.25(OH)2D were below reference range. Plasma concentrations of albumin-corrected calcium, alkaline phosphatase, and parathyroid hormone were in the upper range of the reference range. Mean Z-scores of LBM were -0.69 +/- 1.34 in group 1 vs -1.01 +/- 1.12 in group 2 and Z-scores of FM were -0.27 +/- 1.70 in group 1 vs -0.95 +/- 1.01 in group 2 (p <0.05). CONCLUSION: Patients with chronic pancreatitis, in particular patients with advanced disease and steatorrhea, are at risk of developing significant bone loss. Despite normal body mass index the patients are characterized by loss of lean body mass and fat mass. The present study shows that these patients have decreased serum levels of vitamin D metabolites and low bone mass.

Adult↗
PubMed2000

Opioid treatment of painful chronic pancreatitis.

BACKGROUND: Abdominal pain is the dominant symptom in 50-75% of patients with chronic pancreatitis, often requiring opioid analgesics. Fentanyl, a potent synthetic opioid, can be administered percutaneously at a constant dose and is claimed to have fewer systemic side effects. AIM: To evaluate transdermal fentanyl plaster versus sustained release morphine tablets as analgesic treatment of painful chronic pancreatitis. METHODS: In an open randomized crossover trial, 18 patients were included. The treatment period was 4 wk for each drug. All patients had immediate-release morphine tablets as rescue medication. RESULTS: The dosage of transdermal fentanyl had to be increased on average 50% over that indicated by the manufacturer. When this was done and rescue medication was secured, no difference between the two drugs in primary endpoint or patient preference was observed. There was also no difference in the secondary endpoints, pain control, and quality of life. However, skin side effects, mostly mild, occurred in 44% of the patients during treatment with transdermal fentanyl, and the mean daily dose of immediate release morphine was significantly higher during the transdermal fentanyl period than during the sustained-release morphine period (30.7 mg vs. 14.7 mg [p < 0.01]). CONCLUSION: When given in an appropriate dose, transdermal fentanyl might be useful for treatment of some patients with painful chronic pancreatitis, e.g., when tablet ingestion is difficult. However, the dosage often has to be increased above that recommended by the manufacturer. The need of rescue morphine is considerable and skin side effects often occur. Transdermal fentanyl is, therefore, not the ideal first-choice analgesic in patients with painful chronic pancreatitis.

Administration, Cutaneous↗
PubMed2000

An unusual case of chylothorax complicating non-Hodgkin's lymphoma.

A 64 year old man with non-Hodgkin's lymphoma developed extremely troublesome chylous pleural effusions following effective chemotherapy. With the pre-operative use of olive oil, a diffuse leakage of lymph was seen at thoracotomy. Oversewing was performed eventually resulting in an excellent outcome.

Chylothorax↗
PubMed2000

Increased risk of recurrent venous thromboembolism during hormone replacement therapy--results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET).

Recent observational studies suggest a 2-4 fold increased risk of venous thromboembolism (VTE) in women taking hormone replacement therapy (HRT). The present study was started before publication of these studies, and the aim was to determine if HRT alters the risk of VTE in high risk women. The study was a randomized. double-blind, and placebo-controlled clinical trial with a double-triangular sequential design. Females with previously verified VTE were randomized to 2 mg estradiol plus 1 mg norethisterone acetate, 1 tablet daily (n = 71) or placebo (n = 69). The primary outcome was recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE). Between 1996 and 1998 a total of 140 women were included. The study was terminated prematurely based on the results of circumstantial evidence emerging during the trial. Eight women in the HRT group and one woman in the placebo group developed VTE. The incidence of VTE was 10.7% in the HRT group and 2.3% in the placebo group. In the HRT group, all events happened within 261 days after inclusion. The sequential design did not stop the study, but strongly indicated a difference between the two groups. Our data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT. This treatment should therefore be avoided in this patient group if possible. The results also support those of recent epidemiological studies, which also indicate increased risk of VTE in non-selected female populations during HRT.

Actuarial Analysis↗
PubMed1999

The X-ray crystal structure of beta-ketoacyl [acyl carrier protein] synthase I.

The crystal structure of the fatty acid elongating enzyme beta-ketoacyl [acyl carrier protein] synthase I (KAS I) from Escherichia coli has been determined to 2.3 A resolution by molecular replacement using the recently solved crystal structure of KAS II as a search model. The crystal contains two independent dimers in the asymmetric unit. KAS I assumes the thiolase alpha(beta)alpha(beta)alpha fold. Electrostatic potential distribution reveals an acyl carrier protein docking site and a presumed substrate binding pocket was detected extending the active site. Both subunits contribute to each substrate binding site in the dimer.

Amino Acid Sequence↗
PubMed1999

Multivariate statistical analysis of organ weights in toxicity studies.

Toxicity studies with drugs in animals are performed to establish the toxicity profile including the no-toxic-effect-level in the animals. One of the responses used in the search for effects is organ weight. Since organ weight is related to body weight of the animal, the analysis of organ weight has to be adjusted. A traditional analysis of covariance with body weight as covariate is not always appropriate since the body weight itself can be affected by the test compound. Hence, a multivariate analysis of variance is suggested, where the correlation between organ weight and body weight is taken into account in testing an overall treatment effect. Two dimensional plots of the contour curves are used to visualize the treatment effect on organ weight and body weight simultaneously. The test procedure suggested for comparing differences between control and treated groups of animals is: start by testing hypotheses of equality of covariance matrices for the different treatment groups and then, depending on the results from the first test, test equality of the mean vectors.

Algorithms↗
PubMed1999

The effect of a Mensendieck exercise program as secondary prophylaxis for recurrent low back pain. A randomized, controlled trial with 12-month follow-up.

STUDY DESIGN: A prospective, randomized, controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group. OBJECTIVE: To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working. SUMMARY OF BACKGROUND DATA: One episode of low back pain increases the risk of further episodes of the condition. The Mensendieck approach combines education and exercise. This approach has been used for many years in Scandinavia and the Netherlands. However, the effects on low back pain have not been evaluated previously in a randomized, controlled trial. METHODS: A total of 77 men and women, mean age 39.6 years (range, 21.2-49.8 years), who had finished treatment for a low back pain episode, were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years. The patients were assigned at random to either the Mensendieck program or a control group. The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks. At 5- and 12-month follow-up examinations, the patients were assessed for recurrence of low back pain, days of sick leave, low back pain, and functional scores. RESULTS: After 12 months, there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group (P < 0.05). There was a trend toward fewer days of sick leave because of low back pain in the Mensendieck group, but no significant differences between the groups. There was reduction in pain and improvement in function in both groups, with no significant differences between the groups. CONCLUSIONS: A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition. However, there were no differences between the groups with regard to days of sick leave, low back pain, and function.

Activities of Daily Living↗