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Biomedical subjects

M Petersen

Publications and source records attributed to M Petersen.

At least 19 recordsLinked to original sources
PubMed2006

Urinary bromide and breathing zone concentrations of 1-bromopropane from workers exposed to flexible foam spray adhesives.

1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting solvents and suspect carcinogens and is in aerosol products, adhesives and solvents used for metal, precision and electronics cleaning. Toxicity of 1-BP is poorly understood, but it may be a neurologic, reproductive and hematologic toxin. Sparse exposure information prompted this exposure assessment study using air sampling, and measurement of urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving removal of bromide (Br) from the propyl group. One research objective was to evaluate the utility of urinary Br analysis for assessing 1-BP exposure using a relatively inexpensive, commercially available method. Complete 48 h urine specimens were obtained from 30 workers on two consecutive days at two facilities using 1-BP adhesives to construct polyurethane foam seat cushions and from seven unexposed control subjects. All of the workers' urine was collected into composite samples representing three daily time intervals (at work; after work but before bedtime; and upon wake-up) and analyzed for Br ion by inductively coupled plasma-mass spectrometry. Full-shift breathing zone samples were collected for 1-BP on Anasorb carbon molecular sieve sorbent tubes and analyzed by gas chromatography-flame ionization detection via NIOSH method 1025. Geometric mean (GM) breathing zone concentrations of 1-BP were 92 parts per million (p.p.m.) for adhesive sprayers and 11 p.p.m. for other jobs. For sprayers, urinary Br concentrations ranged from 77 to 542 milligrams per gram of creatinine [mg (g-cr)(-1)] at work; from 58 to 308 mg (g-cr)(-1) after work; and from 46 to 672 mg (g-cr)(-1) in wake-up samples. Pre-week urinary Br concentrations for sprayers were substantially higher than for the non-sprayers and controls, with GMs of 102, 31 and 3.8 mg (g-cr)(-1), respectively. An association of 48 h urinary Br concentration with 1-BP exposure was statistically significant (r(2) = 0.89) for all jobs combined. This study demonstrates that urinary elimination is an important excretion pathway for 1-BP metabolism, and Br may be a useful biomarker of exposure.

Adhesives↗
PubMed2006

Randomized, multi-center trial of two hypo-energetic diets in obese subjects: high- versus low-fat content.

OBJECTIVE: To investigate whether a hypo-energetic low-fat diet is superior to a hypo-energetic high-fat diet for the treatment of obesity. DESIGN: Open-label, 10-week dietary intervention comparing two hypo-energetic (-600 kcal/day) diets with a fat energy percent of 20-25 or 40-45. SUBJECTS: Obese (BMI >or=30 kg/m(2)) adult subjects (n = 771), from eight European centers. MEASUREMENTS: Body weight loss, dropout rates, proportion of subjects who lost more than 10% of initial body weight, blood lipid profile, insulin and glucose. RESULTS: The dietary fat energy percent was 25% in the low-fat group and 40% in the high-fat group (mean difference: 16 (95% confidence interval (CI) 15-17)%). Average weight loss was 6.9 kg in the low-fat group and 6.6 kg in the high-fat group (mean difference: 0.3 (95% CI -0.2 to 0.8) kg). Dropout was 13.6% (n = 53) in the low-fat group and 18.3% (n = 70) in the high-fat group (P=0.001). Among completers, more subjects lost >10% in the low-fat group than in the high-fat group ((20.8%, n = 70) versus (14.7%, n = 46), P = 0.02). Fasting plasma total, low-density lipoprotein- and high-density lipoprotein-cholesterol decreased in both groups, but more so in the low-fat group than in the high-fat group. Fasting plasma insulin and glucose were lowered equally by both diets. CONCLUSIONS: The low-fat diet produced similar mean weight loss as the high-fat diet, but resulted in more subjects losing >10% of initial body weight and fewer dropouts. Both diets produced favorable changes in fasting blood lipids, insulin and glucose.

Adult↗
PubMed2005

Tracheal surgery in children.

BACKGROUND: The aim of this study is to show that five distinct types of tracheal anomalies should be differentiated with respect to therapy and prognosis. METHODS: The records of 12 infants and children seen over a period of 20 years for different tracheal anomalies such as laryngotracheal stenosis (n = 3), long or short-segment stenosis of the upper (n = 2), middle (n = 6), and lower (n = 1) trachea were reviewed. In addition to these 12 patients with congenital stenosis, 3 other patients needed tracheal resections because of oncologic or traumatic disease: in 2, the trachea was infiltrated by a papillary carcinoma of the thyroid gland and in one, the upper part of the trachea was injured by an oral explosion accident. 25 patients presenting during the same period for other tracheal pathologies including esophagotracheal cleft syndrome (n = 7), tracheomalacia (n = 4), total tracheal agenesis (n = 3), or for placement of a tracheostomy (n = 11) due to other diseases were excluded from this study. RESULTS: There was 1 early death after repair of a laryngotracheal stenosis by cricoid-split and cricoid-splint due to both cerebral hemorrhage and cardiac insufficiency secondary to Fallot's tetralogy. Another child died four weeks after slide tracheoplasty as a result of hypoxic cerebral lesions induced by severe central catheter-related septicemia. One child with therapy-resistant obstructing granulation tissue which developed after a slide tracheoplasty required a tracheostomy. The patient with the tracheal injury died after another accident one year after discharge. All other patients (n = 11) are doing well. CONCLUSIONS: With respect to therapy of congenital and post-intubation tracheal stenosis, four types should be distinguished. Each of these types requires an adequate surgical procedure. The most important postoperative problem in tracheal surgery is the development of granulation tissue. However, the pathogenesis of granulation is still unknown.

Bronchoscopy↗
PubMed2005

Pathogenesis of extrahepatic bile duct atresia (EHBA): comprehension from a surgical point of view.

INTRODUCTION: The aim of the study is to establish a complete comprehension of the pathogenesis of Biliary Atresia, and to explain both the variable and redundant pathomorphological, as well as, histological findings. MATERIALS AND METHODS: The pathomorphological and histological findings in 223 patients with histologically evident EHBA were recorded retrospectively (72 patients) or prospectively (151 patients), according to a projected ascending study. These findings were compared with histological findings in human and rat embryos. RESULTS: 1) The pathomorphological findings recorded in patients with EHBA were also found in stages of normal embryogenesis of the bile duct system in human and rat embryos. 2) Each histological finding in Biliary Atresia corresponds to a finding in an interrupted stage of the normal development in human and rat embryos. 3) The findings in patients and embryos can be explained completely by a disturbed intrinsic epithelium/mesoderm interaction. 4) Some findings in Biliary Atresia cannot be explained easily by the assumption of an extrinsic factor. CONCLUSION: There is no finding in Biliary Atresia which cannot be completely explained as the result of an intrinsic developmental error, probably due to disturbances or interruption of epithelium/mesoderm interaction during embryogenesis.

Animals↗
PubMed2003

Low-threshold heat receptor in chick sensory neurons is upregulated independently of nerve growth factor after nerve injury.

In mammals, the cloned low-threshold heat receptor, vanilloid receptor subtype 1 (VR1), is involved in the genesis of thermal hyperalgesia after inflammation. However, there is evidence that VR1 is not involved in the thermal hyperalgesia that occurs after nerve injury. In search for other heat receptors which might be involved in this phenomenon, we previously demonstrated that chick dorsal root ganglion neurons, which are insensitive to capsaicin, respond to low-threshold heat. Here, we investigated whether expression of the low-threshold noxious heat receptor in chicks is regulated by nerve growth factor (NGF), as VR1 is in mammals. Heat (44 degrees C) responsiveness of isolated dorsal root ganglion neurons of chicks was investigated (i) under culture conditions for up to 4 days with and without NGF and (ii) after a tight ligation of the sciatic nerve for up to 6 days, using cobalt-uptake method. In every case, a significant upregulation in the proportion of heat-responsive neurons was observed. On the molecular level, there was an increase of chick VR1 mRNA level in dorsal root ganglion cells cultured for 3 days in medium lacking NGF. In rat dorsal root ganglion neurons cultured for 1-4 days without NGF, patch-clamp experiments revealed that after 1 day almost all neurons responding to heat also responded to capsaicin, whereas after 3-4 days, more than one-half of the heat-responsive neurons did not respond to capsaicin. These data suggest the existence of low-threshold heat receptors in chick dorsal root ganglion neurons, the expression of which is regulated independently of NGF.

Animals↗
PubMed2003

Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes.

OBJECTIVE: Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus. However, fish oil may have deleterious effects on lipid peroxidation and glycemic control. DESIGN: In this study, 44 type 2 diabetic patients were randomized to vitamin E standardized (53.6 mg/day) supplementation (capsules) with 4 g daily of either fish oil (n=23) or corn oil (n=21) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation. LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu(2+). As a marker of in vivo oxidation malondialdehyde concentration in LDL (LDL-MDA) was measured. RESULTS: Fish oil reduced both mean lag time (before, 57.8; after, 48.8 min, P<0.001) and mean propagation rate (before, 0.018 DeltaOD/min; after, 0.015 DeltaOD/min, P<0.001), whereas corn oil had no influence on lag time and propagation rate. The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment. LDL-MDA changes differed borderline significantly between groups (FO, 110.4 pmol/mg protein; CO, 6.7 pmol/mg protein; P=0.057). Fish oil supplementation had no influence on glycemic control as assessed from HbA(1c) and fasting blood glucose. CONCLUSION: According to our findings, fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles. More studies are needed to clarify the clinical importance of this finding.

Adult↗
PubMed2003

Immunohistochemical and molecular biological investigations regarding the pathogenesis of extrahepatic biliary atresia. (Part 1: immunohistochemical studies).

INTRODUCTION: The pathogenetic model for biliary atresia presently most favored is that EHBA is the result of a peri- or postnatal bile duct lesion. Several authors demonstrated inflammatory infiltrations in the mesenchymal areas of the liver and thus concluded an infectious genesis. An association of rota-, reo- (and CMV) virus infection with EHBA was suspected, but the presence of these viruses in EHBA could not be reproduced. In view of this controversial debate we found it to be indicated to investigate tissue blocks from the porta hepatis and liver biopsies in children with EHBA by histo- and immunohistochemistry for the quality and quantity of leukocyte infiltrations. METHODS: 31 tissue excidates of the porta hepatis were gained on the occasion of hepatoportoenterostomy, fixed in 4 % buffered formalin and embedded in paraffin. The presence of leukocyte infiltrations and their subpopulations was demonstrated by histochemical reactions and immunohistochemical staining methods using specific antibodies against surface markers. The number of leukocytes and their subpopulations was counted in three different regions of the porta hepatis, the obliterated extrahepatic bile duct, the fibrous mass of the porta hepatis and the transition zone between the fibrous mass and liver parenchyma. A statistical analysis was done. RESULTS: In EHBA, leukocyte infiltrations consist mainly of macrophages. Antigen-presenting cells and lymphatic cells play a minor role. Lymphatic cells could only be detected in 6 out of 31 tissue preparations. Antigen-presenting cells could only be detected via anti-F13a antibody which shows cross-reactivities, i.e. against macrophages and embryonal tissue. Evaluating the density of leukocyte infiltrations with regard to the different anatomical regions of the porta hepatis we could demonstrate that leukocyte infiltrations are scarce around the rudiment of the bile duct whereas the highest leukocyte density could be found in the fibrous mass of the porta hepatis and the intrahepatic fibrous septs interconnecting the fibrous mass of the porta hepatis with liver parenchyma. Liver parenchyma was mainly free of leukocyte infiltrations with the exception of neutrophilic granulocytes. Regardless of the subpopulations, leukocytes were mainly arranged around the bile ducts of the fibrotic septa. CONCLUSIONS: Most tissue preparations from children operated on during the 4th-8th week of life show only small leukocyte infiltrations and in the majority of cases no immunocompetent lymphocytes. This leads to the conclusion that a virus infection as an underlying cause for EHBA is very unlikely. Most probably, the observed leukocyte infiltrations are due to an unspecific phagocytotic activity. Comparing our results to reports from Hadchouel et al (9) and Landing et al (12) led us to believe that a pathologic immunoreaction with a possible defective antigen elimination could also be considered as a reason for EHBA.

Antigens, CD↗
PubMed2001

Level set approach to reversible epitaxial growth.

We generalize the level set approach to model epitaxial growth to include thermal detachment of atoms from island edges. This means that islands do not always grow and island dissociation can occur. We make no assumptions about a critical nucleus. Excellent quantitative agreement is obtained with kinetic Monte Carlo simulations for island densities and island size distributions in the submonolayer regime.

Journal Article↗
PubMed2001

No evidence for bradykinin B1 receptors in rat dorsal root ganglion neurons.

Bradykinin receptors are believed to contribute to hyperalgesia under conditions of neuropathic pain. Using calcium imaging we investigated responses to B1 and B2 agonists on isolated rat dorsal root ganglion neurons. No response to the B1 agonist was detected, whereas 12% of neurons responded to the B2 agonist. Northern blot analysis confirmed the lack of B1 receptor expression in dorsal root ganglia, as B1 mRNA was neither detected under normal conditions nor after nerve injury. In the calcium imaging experiments, agonists were applied with an elevated superfusion flow rate to avoid tachyphylaxis to the drug. Normal external solution applied at this flow rate constituted a mechanical stimulus causing a response in some neurons. Thus, in comparable set-ups mechanosensitivity has first to be tested to avoid masking effects.

Animals↗
PubMed2001

Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine.

Hyperphenylalaninemia due to a deficiency of phenylalanine hydroxylase (PAH) is an autosomal recessive disorder caused by >400 mutations in the PAH gene. Recent work has suggested that the majority of PAH missense mutations impair enzyme activity by causing increased protein instability and aggregation. In this study, we describe an alternative mechanism by which some PAH mutations may render PAH defective. Database searches were used to identify regions in the N-terminal domain of PAH with homology to the regulatory domain of prephenate dehydratase (PDH), the rate-limiting enzyme in the bacterial phenylalanine biosynthesis pathway. Naturally occurring N-terminal PAH mutations are distributed in a nonrandom pattern and cluster within residues 46-48 (GAL) and 65-69 (IESRP), two motifs highly conserved in PDH. To examine whether N-terminal PAH mutations affect the ability of PAH to bind phenylalanine at the regulatory domain, wild-type and five mutant (G46S, A47V, T63P/H64N, I65T, and R68S) forms of the N-terminal domain (residues 2-120) of human PAH were expressed as fusion proteins in Escherichia coli. Binding studies showed that the wild-type form of this domain specifically binds phenylalanine, whereas all mutations abolished or significantly reduced this phenylalanine-binding capacity. Our data suggest that impairment of phenylalanine-mediated activation of PAH may be an important disease-causing mechanism of some N-terminal PAH mutations, which may explain some well-documented genotype-phenotype discrepancies in PAH deficiency.

Amino Acid Sequence↗
PubMed2001

Prevalence and risk factors of tendinitis and related disorders of the distal upper extremity among U.S. workers: comparison to carpal tunnel syndrome.

BACKGROUND: National estimates of tendinitis and related disorders of the distal upper extremity among U.S. workers have not been available with the exception of carpal tunnel syndrome. METHODS: The Occupational Health Supplement Data of the 1988 National Health Interview Survey were analyzed for tendinitis and related disorders of the hand/wrist and elbow (distal upper extremity) using the Survey Data Analysis (SUDAAN) software. RESULTS: Among the 30,074 respondents (statistically weighted population of 127 million) who had worked anytime during the previous 12 months, 0.46% (95% CI: 0.36, 0.56) reported that they experienced a "prolonged" hand discomfort which was called tendinitis, synovitis, tenosynovitis, deQuervain's disease, epicondylitis, ganglion cyst, or trigger finger, by a medical person. This corresponds to 588,000 persons (95% CI: 457,000; 712,000) reporting one of these disorders, 28% (or 164,000) of which were thought to be work-related by the medical person. Among various risk factors examined by multiple logistic regression analysis, bending/twisting of the hands/wrists at work and female gender were significantly associated with reporting of these disorders. CONCLUSIONS: By combining these cases with the previously reported cases of work-related carpal tunnel syndrome, we estimate that there were approximately 520,000 cases of work-related musculoskeletal disorders of the distal upper extremity among US workers in 1988.

Adolescent↗
PubMed2001

Classification of wheat varieties: use of two-dimensional gel electrophoresis for varieties that can not be classified by matrix assisted laser desorpiton/ionization-time of flight-mass spectrometry and an artificial neural network.

Analyzing a gliadin extract by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) combined with an artificial neural network (ANN) is a suitable method for identification of wheat varieties. However, the ANN can not distinguish between all different wheat varieties. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was applied to three pairs of wheat varieties, which can not be classified correctly by ANN. By 2-D PAGE the varieties in the three pairs can be discriminated and these six wheat varieties can be separated from each other, which could not be separated by MALDI-TOF-MS and NN.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2001

Identification of barley and rye varieties using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry with neural networks.

Cereal varieties are normally identified using time-consuming methods such as visual examination of either the intact grain or one-dimensional electrophoretic patterns of the grain storage proteins. A fast method for identification of wheat (Triticum aestivum L.) varieties has previously been developed, which combines analysis of alcohol-soluble wheat proteins (gliadins) using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry with neural networks. Here we have applied the same method for the identification of both barley (Hordeum vulgare L.) and rye (Secale cereale L.) varieties. For barley, 95% of the mass spectra were correctly classified. This is an encouraging result, since in earlier experiments only a grouping into subsets of varieties was possible. However, the method was not useful in the classification of rye, due to the strong similarity between mass spectra of different varieties.

Glutens↗
PubMed2001

In vitro expression of 34 naturally occurring mutant variants of phenylalanine hydroxylase: correlation with metabolic phenotypes and susceptibility toward protein aggregation.

Phenylalanine hydroxylase (PAH) is a homotetrameric enzyme that catalyzes the conversion of phenylalanine to tyrosine, the rate-limiting step of phenylalanine disposal in humans. Primary dysfunction of PAH caused by mutations in the PAH gene results in hyperphenylalaninemia, which may impair cognitive development unless corrected by dietary restriction of phenylalanine. The mechanism(s) by which PAH missense mutations cause enzyme impairment has been studied in detail only in a small number of cases, but existing evidence points to a major role of enhanced proteolytic degradation due to aberrant folding of mutant polypeptides. We have used two heterologous in vitro expression systems (a mammalian cell-free transcription-translation system and the pET system of Escherichia coli) to examine 34 mutations that have been associated with PAH deficiency in the Danish population. These mutations represent a broad range of amino acid substitutions, functional enzyme domains, and metabolic phenotypes. In both systems, residual in vitro activities correlated broadly with metabolic phenotypes, however, with significant discrepancies. Analysis of E. coli extracts by nondenaturing polyacrylamide gel electrophoresis and storage experiments showed that (i) in general, mutations in the N-terminal regulatory domain are associated with relatively stable proteins compared to most mutations in the central catalytic domain, and (ii) for mutations in the catalytic domain, high levels of protein aggregation do not always correspond with a severe phenotype. Our data support and extend previous evidence that PAH mutations exert their pathogenic effects by several distinct mechanisms that may operate individually or in concert.

Animals↗
PubMed2001

The production of cytotoxic lignans by plant cell cultures.

Cytotoxic lignans derived from podophyllotoxin are currently used in cancer chemotherapy. Podophyllotoxin for semi-synthetic derivatization is isolated from the rhizomes of Podophyllum plants growing wild, some of which are counted as endangered species. An alternative source for podophyllotoxin or related lignans may in future be cell cultures derived from different plant species, such as Podophyllum spp or Linum spp. These cell cultures were shown to accumulate considerable amounts of podophyllotoxin or 5-methoxypodophyllotoxin. Optimization of the cell cultivation regime might lead to a renewable source of cytotoxic lignans for medicinal uses. This Mini-Review summarizes the attempts to establish plant cell cultures for the production of podophyllotoxin and related lignans and their optimization towards high levels of these target compounds. It also summarizes the results of studies on the biosynthesis of podophyllotoxin and 5-methoxypodophyllotoxin.

Cell Culture Techniques↗
PubMed2001

Deoxypodophyllotoxin 6-hydroxylase, a cytochrome P450 monooxygenase from cell cultures of Linum flavum involved in the biosynthesis of cytotoxic lignans.

Cell-suspension cultures of Linum flavum L. (Linaceae) synthesize and accumulate aryltetrahydronaphthalene lignans with 6-methoxypodophyllotoxin as the main component. The experimental data indicate that the biosynthesis of 6-methoxypodophyllotoxin occurs via deoxypodophyllotoxin, beta-peltatin, and beta-peltatin-A methyl ether. The enzyme catalyzing the introduction of the hydroxyl group in position 6 is deoxypodophyllotoxin 6-hydroxylase (DOP6H). The enzyme was shown to be a cytochrome P450-dependent monooxygenase by blue-light reversion of carbon monoxide inhibition and inhibition by cytochrome c. DOP6H is a membrane-bound microsomal enzyme with a pH optimum of 7.6 and a temperature optimum of 26 degrees C. Deoxypodophyllotoxin is specifically accepted with an apparent Km of 20 microM and a saturation concentration of 200 microM; 4'-demethyldeoxypodophyllotoxin is the only other tested substrate accepted for hydroxylation. DOP6H predominantly accepts NADPH as electron donor; NADH can only sustain low hydroxylation activities. A synergistic effect of NADPH and NADH is not observed. The enzyme is saturated around 250 microM NADPH; the apparent Km for this substrate is 36 microM.

Cells, Cultured↗