Search PubMed⌕ Search

Biomedical subjects

B Christensen

Publications and source records attributed to B Christensen.

At least 37 records · Page 2Linked to original sources

Abstention from filtered coffee reduces the concentrations of plasma homocysteine and serum cholesterol--a randomized controlled trial.

BACKGROUND: Elevated concentrations of plasma total homocysteine (tHcy) and serum total cholesterol are risk factors for ischemic heart disease (IHD). Previous studies showed that the consumption of very high doses of unfiltered coffee increases tHcy and total cholesterol. OBJECTIVE: A prospective intervention study was performed to assess the effects of coffee consumption on the concentrations of tHcy and total cholesterol by using doses and brewing methods common in southeastern Norway. DESIGN: The study was an unblinded, controlled trial with 191 healthy, nonsmoking, coffee-drinking volunteers aged 24-69 y randomly assigned to 3 groups who were asked to consume for 6 consecutive weeks no coffee, 1-3 cups (approximately 175-525 mL)/d, or > or =4 cups (approximately 700 mL)/d prepared in the manner to which they were accustomed. Blood samples were drawn when the subjects were randomly assigned and at 3 and 6 wk of the trial. Dietary data were collected by questionnaire. RESULTS: Ninety-seven percent of the participants reported being regular consumers of caffeinated filtered coffee. Abstention from coffee for 6 wk was associated with a decrease in the tHcy concentration of 1.08 micromol/L and a decrease in the total cholesterol concentration of 0.28 mmol/L in participants who had been drinking on average 4 cups of filtered coffee daily for the past year. Adjustments for several possible confounders did not alter the results. CONCLUSION: Abstention from filtered coffee in doses that are commonly consumed was associated with lower concentrations of tHcy and total cholesterol.

Adult↗

Network identification and flux quantification in the central metabolism of Saccharomyces cerevisiae under different conditions of glucose repression.

The network structure and the metabolic fluxes in central carbon metabolism were characterized in aerobically grown cells of Saccharomyces cerevisiae. The cells were grown under both high and low glucose concentrations, i.e., either in a chemostat at steady state with a specific growth rate of 0.1 h(-1) or in a batch culture with a specific growth rate of 0.37 h(-1). Experiments were carried out using [1-(13)C]glucose as the limiting substrate, and the resulting summed fractional labelings of intracellular metabolites were measured by gas chromatography coupled to mass spectrometry. The data were used as inputs to a flux estimation routine that involved appropriate mathematical modelling of the central carbon metabolism of S. cerevisiae. The results showed that the analysis is very robust, and it was possible to quantify the fluxes in the central carbon metabolism under both growth conditions. In the batch culture, 16.2 of every 100 molecules of glucose consumed by the cells entered the pentose-phosphate pathway, whereas the same relative flux was 44.2 per 100 molecules in the chemostat. The tricarboxylic acid cycle does not operate as a cycle in batch-growing cells, in contrast to the chemostat condition. Quantitative evidence was also found for threonine aldolase and malic enzyme activities, in accordance with published data. Disruption of the MIG1 gene did not cause changes in the metabolic network structure or in the flux pattern.

Acetyl Coenzyme A↗

zeta-, epsilon-, and gamma-Globin mRNA in blood samples and CD71(+) cell fractions from fetuses and from pregnant and nonpregnant women, with special attention to identification of fetal erythroblasts.

BACKGROUND: Information about the appearance of gamma-, epsilon-, and zeta-globin mRNAs in fetal erythroblasts during gestation and about the presence and amounts of these mRNAs in pregnant and nonpregnant women is important from the perspective of using these molecules as a marker of fetal erythroblasts. A specific marker is necessary for isolation and identification of fetal nucleated red blood cells from maternal blood samples for use in antenatal diagnosis of fetal genetic or chromosomal abnormalities. METHODS: We used a very sensitive reverse transcription-PCR (RT-PCR) method, coamplification analysis of gamma- and epsilon-globin cDNA, and quantitative analysis of gamma-globin mRNA based on competitive RT-PCR to investigate these aspects. RESULTS: All adult whole-blood samples were negative for epsilon- and zeta-globin mRNA. Analyses of CD71(+) cell fractions showed that specimens from 19 of 20 nonpregnant and 10 of 14 pregnant women (at 9-13 weeks of gestation) were positive for gamma-globin mRNA (Fisher's exact test, P = 0.13), and those from 3 of 20 nonpregnant and 5 of 14 pregnant women were positive for zeta-globin mRNA (Fisher's exact test, P = 0.23). No epsilon-globin mRNA was detected in CD71(+) cell fractions from 1-mL blood samples from adults. CD71(+) cell fractions from eight fetal blood samples (at 17-20 weeks of gestation) were positive for all three globin mRNAs. We found no statistically significant difference between the amounts of gamma-globin mRNA in pregnant and nonpregnant women. CONCLUSIONS: This study indicates that epsilon-globin mRNA might function as a marker for fetal CD71(+) cells early in pregnancy. Although gamma-globin mRNA can be detected in CD71(+) cell fractions from most adults, these transcripts also may be of use because of a marked difference between adult and fetal values.

Adult↗

Serum homocysteine concentration as an indicator of survival in patients with acute coronary syndromes.

BACKGROUND: Circulating homocysteine levels are predictive of survival in patients with stable coronary artery disease. The prognostic value of serum homocysteine levels, obtained in the acute phase in patients with myocardial infarction or unstable angina, is unknown. OBJECTIVES: To test the hypothesis that circulating homocysteine levels, obtained during the first 24 hours following hospital admission in patients with acute coronary syndromes, are predictive of long-term mortality. METHODS: To test this hypothesis we performed a prospective inception cohort study at a teaching hospital in Gothenburg, Sweden. A total of 579 patients (179 women and 400 men; median age, 67 years) were included (Q-wave myocardial infarction in 163 patients, non-Q-wave myocardial infarction in 210 patients, unstable angina pectoris in 206 patients). MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: During a median follow-up of 628 days, 65 patients died. The serum homocysteine level (mean [SD]) was significantly lower in long-term survivors (n = 514) than in nonsurvivors (n=65) (12.3 [7.0] vs 14.3 [5.9] pmol/L; P=.003). The relative risk (all-cause mortality) for patients with homocysteine levels in the upper quartile was 2.4 (95% confidence interval, 1.5-4.0) compared with that of patients in the 3 lower quartiles. After adjustment for relevant confounders, the relative risk estimate remained significant (relative risk= 1.69; 95% confidence interval, 1.02-2.80). In a stepwise model the homocysteine level provided prognostic information additional to that of patient age, diabetes mellitus, and diuretic usage prior to hospital admission (P=.03). CONCLUSION: The serum homocysteine level on hospital admission is an independent predictor of long-term survival in patients with acute coronary syndromes.

Acute Disease↗

Metabolic network analysis of Penicillium chrysogenum using (13)C-labeled glucose.

Using (13)C-labeled glucose fed to a penicillin-overproducing strain of Penicillium chrysogenum, the intracellular fluxes were quantified, and the presence of two new pathways, not previously described in this organism, is suggested. Thus, glycine was synthesized not only by serine hydroxymethyltransferase, but also by threonine aldolase. The formation of cytosolic acetyl-CoA was found to be synthesized both via the citrate lyase-catalyzed reaction and by degradation of the penicillin side-chain precursor, phenoxyacetic acid. Furthermore, the experimental data indicate that the main activities of homocitrate synthase and alpha-isopropylmalate synthase are located in the cytosol. All experimental data on the labeling patterns were obtained using gas chromatography-mass spectrometry, which is faster and more sensitive than the nuclear magnetic resonance methods usually applied for analysis of labeling patterns.

Acetyl Coenzyme A↗

[Roller skating accidents. Registration of roller skating injuries in two emergency departments].

Rising popularity of roller-skates in recent years has resulted in increasing numbers of accidents involving roller-skates. The subject of our study was a consecutive number of patients who were treated at the casualty departments of Svendborg and Middelfart hospitals, Denmark, between July 1997 and June 1998. A total number of 169 patients representing 179 injuries were registered. A high incidence of injuries was found among children of school age. Protective equipment was used, in 31% (n = 52) of cases, which shows an increase compared to previous studies in Denmark (1). Injuries of the distal antebrachium, wrist and metacarpals account for 45% of all injuries. Wrist guards protect the area but do not completely eliminate the risk of fractures and injuries. A larger usage of protective equipment will probably result in a decrease in the number of injuries, and therefore information about protective measures is essential.

Adolescent↗

Sibs with anencephaly, anophthalmia, clefts, omphalocele, and polydactyly: hydrolethalus or acrocallosal syndrome?

Major characteristics of the acrocallosal syndrome include severe mental retardation, agenesis or hypoplasia of the corpus callosum, and polydactyly of fingers and toes. In the past few years, anencephaly has also been noted, together with other midline defects. We report on a nonconsanguineous, Norwegian couple with a history of two pregnancies with a male and a female fetus, respectively, with anencephaly, median cleft lip and palate, omphalocele, and preaxial polydactyly, suggesting the diagnosis of the acrocallosal syndrome. Both fetuses also lacked eyes and nose, a finding not previously reported in the acrocallosal syndrome. Microphthalmia has been reported in the hydrolethalus syndrome, which may be caused by mutations in the same gene as the acrocallosal syndrome. The present report adds support to the hypothesis that the acrocallosal and hydrolethalus syndromes may be allelic conditions. The family history is consistent with autosomal recessive inheritance.

Abnormalities, Multiple↗

Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria.

Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) is the most common inborn error of folate metabolism. Patients are characterized by severe hyperhomocysteinemia, homocystinuria and a variety of neurological and vascular problems. Eighteen rare mutations have been reported in this group of patients. Two polymorphisms which cause mild enzyme deficiencies have been described (677C-->T and 1298A-->C). The first sequence change encodes a thermolabile enzyme and is associated with mild hyperhomocysteinemia. Six novel point mutations are described in patients with severe deficiency of MTHFR, along with their associated polymorphisms and clinical phenotypes. Of the two nonsense mutations (1762A-->T, 1134C-->G) and four missense mutations (1727C-->T, 1172G-->A, 1768G-->A, and 358G-->A), one was identified in the N-terminal catalytic domain, while the others were located in the regulatory C-terminal region. All four residues affected by missense mutations are conserved in one or more MTHFRs of other species. This report brings the total to 24 mutations identified in severe MTHFR deficiency, with two mutations identified in each of 22 patients.

Adolescent↗

Construction and characterization of an oxalic acid nonproducing strain of Aspergillus niger.

Aspergillus niger produces oxalic acid as a by-product which causes problems with downstream processing of industrial enzymes. To overcome this problem the oah gene encoding oxaloacetate hydrolase (EC 3.7.1.1) was disrupted in a glucoamylase-producing strain of A. niger and the resulting strain was incapable of producing oxalic acid. The strain with the disrupted gene was compared with the wild-type strain producing oxalic acid in batch cultivations. The specific growth rate of both strains was 0.20 h(-1). The citric acid yields were identical, but the glucoamylase yield was only 50% in the disruptant compared with the wild-type strain. Batch experiments with 13C-labeled glucose as substrate were carried out to determine the metabolic fluxes through the central metabolism. The two strains had almost identical metabolic fluxes, which suggested that it was possible to disrupt the oah gene without pleiotropic consequences. The flux through the pentose phosphate pathway was around 60% of the glucose uptake for both strains, which suggested that a sufficient supply of NADPH was available for biosynthesis.

Aspergillus niger↗

Metabolic characterization of high- and low-yielding strains of Penicillium chrysogenum.

A recently developed method for analyzing metabolic networks using 13C-labels was employed for investigating the metabolism of a high- and a low-yielding strain of Penicillium chrysogenum. Under penicillin-producing conditions, the flux through the pentose phosphate (PP) pathway in the high- and the low-yielding strains was estimated to 70 and 66, respectively. When the high-yielding strain was cultivated in a medium without the penicillin side chain precursor, phenoxyacetic acid, the PP pathway flux was estimated as 71. Thus, in all three experiments, the flux through the PP pathway was almost constant with an average value of 69+/-3, and the method therefore allows for a very reproducible estimation of the PP pathway flux. Phenoxyacetic acid was found to be a source of cytosolic acetyl-CoA and thereby a source of precursors for the biosynthesis of 2-aminoadipic acid, which is a central amino acid in penicillin biosynthesis. However, the labeling patterns also indicated the presence of an unrecognized pathway to cytosolic acetyl-CoA.

Acetates↗

Sex differences in posttraumatic cytokine release of endotoxin-stimulated whole blood: relationship to the development of severe sepsis.

BACKGROUND: In experimental trauma-hemorrhage and sepsis, a sexual dimorphism of cell-mediated immune functions has been described, which has been related to higher susceptibility to and mortality from sepsis in males. Therefore, in the present study, sex differences with regard to cytokine release of endotoxin stimulated whole blood and its relation to the development of severe posttraumatic sepsis were investigated in blunt trauma patients with multiple injuries. METHODS: Eighty-four patients (25 female; 59 male) sustaining blunt injuries with an Injury Severity Score > 16 were enrolled in the study. Whole blood and serum were obtained during a 14-day period of hospitalization. The capacity of peripheral blood mononuclear cells to produce cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, IL-8) was tested by using a whole blood assay. Serum samples were assayed for anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor beta1) and sex hormones (testosterone, estradiol, progesterone). Patients were monitored daily for sepsis criteria according to the ACCP/ SCCM consensus conference 1992. RESULTS: Within the entire patient population, sex differences in posttraumatic cytokine release were not detectable. Male trauma patients developing severe sepsis (n = 16) presented with a significantly increased cytokine producing capacity in the early posttraumatic period (< or = 24 hours after admission to the emergency room) when compared with males with an uncomplicated recovery. In females, differences between the subgroups of patients with (n = 7) and without development of severe sepsis were not detectable. There were no differences in systemic levels of anti-inflammatory cytokines within the early posttraumatic period between the subgroups of male and female patients with and without development of severe sepsis. In females, differences in sex hormone levels were not detectable, whereas in males, development of severe sepsis later was found to coincide with significantly decreased testosterone and increased estradiol serum levels. CONCLUSION: The present study demonstrates a sex-specific regulation of leukocyte function in patients with multiple injuries within the early posttraumatic period. In male patients with multiple injuries, increased cytokine-producing capacities may correspond to enhanced inflammatory responses, which increase susceptibility to sepsis, whereas in female patients, other regulatory mechanisms may be involved.

Adult↗

Metabolic network analysis. A powerful tool in metabolic engineering.

Metabolic network analysis is a tool for investigating the features that identify the topology of a metabolic network and the relative activities of its individual branches. The pillars of metabolic network analysis are mathematical modeling, allowing for a quantitative analysis, biochemical knowledge of, for example, reaction stoichiometry, and the experimental techniques, providing input for the modeling part. The modeling part includes metabolite balancing, usually the basis for metabolic flux analysis, and isotope balancing. Isotope balancing can be used for both identification of active pathways and for estimation of the relative fluxes through two pathways leading to the same metabolite, aspects that are difficult to investigate using metabolite balancing. The combination of metabolite and isotope balancing is very powerful and constitutes the basis of metabolic network analysis. With the main focus being on investigating the metabolic network structure, this review describes how central metabolic features, for example, pathway identification, flux distribution, and compartmentation, can be addressed using a combination of metabolite balancing and labeling experiments.

Acetyl Coenzyme A↗

Rapid prenatal diagnosis of chromosome aneuploidies by interphase fluorescence in situ hybridization: a one-year clinical experience with high-risk and urgent fetal and postnatal samples.

OBJECTIVES: To evaluate the clinical utility of rapid prenatal and postnatal detection of common chromosome aneuploidies by interphase fluorescence in situ hybridization (FISH) analysis with DNA probes. DESIGN: Four hundred and seventy-seven high-risk and/or urgent amniotic fluid, chorionic villus and fetal and postnatal blood samples were prospectively examined by FISH with probes specific for chromosomes 13, 18, 21, X, and Y and results were reported within 48 hours. All FISH results were followed by conventional chromosome analysis, if possible. SETTING: Cytogenetic service laboratory at the tertiary referral center, Rigshospitalet in Copenhagen. MAIN OUTCOME MEASURES: The fraction of clinically significant chromosome aneuploidies that was detected by FISH analysis, and the fraction of terminations that was based on FISH and ultrasound results rather than on conventional cytogenetic results. RESULTS: The FISH assay detected 76% of the clinically significant chromosome abnormalities as determined by subsequent cytogenetic analysis. Seventy-two percent of the terminations of the chromosomally abnormal pregnancies were based on FISH and ultrasound results rather than on conventional cytogenetic results. CONCLUSION: FISH analysis is a clinically useful adjunctive tool to conventional pre- and postnatal cytogenetic analysis. The assay rapidly detects the majority of clinically significant chromosome abnormalities, thus facilitating difficult pre- and postnatal clinical decisions.

Adult↗

Which antibiotics are appropriate for treating bacteriuria in pregnancy?

Bacteriuria in pregnancy, with or without clinical symptoms, is frequent. If left untreated, it can in 20-30% of cases lead to acute pyelonephritis, which is a serious threat to the mother and fetus, increasing the risk of preterm labour and low birthweight infants. This paper is a review of the literature concerning antibacterial treatment of bacteriuria in pregnancy. It is crucial to ensure that drugs to be used in pregnancy are safe and effective. Established first-line drugs such as ampicillin (pivampicillin) and amoxycillin, and other commonly used treatments such as trimethoprim-sulphamethoxazole, are associated with a high degree of resistance in Escherichia coli, the most common pathogen in the urinary tract. A recent survey of physicians in Denmark, Finland, Norway and Sweden confirms that beta-lactam antibiotics (particularly pivmecillinam) and nitrofurantoin are the drugs of first choice in the treatment of bacteriuria in pregnancy in the Nordic countries. No teratogenic effects have been associated with these agents. In contrast to nitrofurantoin, pivmecillinam is also efficient against pyelonephritis. In spite of resistance in E. coli and possible adverse effects on the fetus, many physicians still prescribe sulphonamides during the first two trimesters of pregnancy.

Journal Article↗

Which antibiotics are appropriate for treating bacteriuria in pregnancy?

Bacteriuria in pregnancy, with or without clinical symptoms, is frequent. If left untreated, it can in 20-30% of cases lead to acute pyelonephritis, which is a serious threat to the mother and fetus, increasing the risk of preterm labour and low birthweight infants. This paper is a review of the literature concerning antibacterial treatment of bacteriuria in pregnancy. It is crucial to ensure that drugs to be used in pregnancy are safe and effective. Established first-line drugs such as ampicillin (pivampicillin) and amoxycillin, and other commonly used treatments such as trimethoprim-sulphamethoxazole, are associated with a high degree of resistance in Escherichia coli, the most common pathogen in the urinary tract. A recent survey of physicians in Denmark, Finland, Norway and Sweden confirms that beta-lactam antibiotics (particularly pivmecillinam) and nitrofurantoin are the drugs of first choice in the treatment of bacteriuria in pregnancy in the Nordic countries. No teratogenic effects have been associated with these agents. In contrast to nitrofurantoin, pivmecillinam is also efficient against pyelonephritis. In spite of resistance in E. coli and possible adverse effects on the fetus, many physicians still prescribe sulphonamides during the first two trimesters of pregnancy.

Anti-Bacterial Agents↗

Improving the nicotinic pharmacophore with a series of (Isoxazole)methylene-1-azacyclic compounds: synthesis, structure-activity relationship, and molecular modeling.

A series of (isoxazole)methylene-1-azacyclic compounds was prepared. The compounds were tested for affinity to central nicotinic acetylcholine receptors (nAChRs) and central muscarinic receptors. The compounds covered a broad range of affinities for the nAChRs (IC(50) = 0.32 to >1000 nM), with selectivities for the nAChRs over the muscarinic receptors in the range of 3-183. The high-affinity compound (Z)-26 (3-(4-methyl-5-isoxazolyl)methylene-1-azabicyclo[2.2. 2]octane, IC(50) = 3.2 nM) having only one energy minimum was used as the reference structure in a computational study. This ligand has enabled definition of an important distance parameter, and the existence of this parameter was supported by showing that other potent nicotinic ligands (for example, nicotine and epibatidine) fit the model.

Animals↗

Diversity of Holocene life forms in fossil glacier ice.

Studies of biotic remains of polar ice caps have been limited to morphological identification of plant pollen and spores. By using sensitive molecular techniques, we now demonstrate a much greater range of detectable organisms; from 2000- and 4000-year-old ice-core samples, we obtained and characterized 120 clones that represent at least 57 distinct taxa and reveal a diversity of fungi, plants, algae, and protists. The organisms derive from distant sources as well as from the local arctic environment. Our results suggest that additional taxa may soon be readily identified, providing a plank for future studies of deep ice cores and yielding valuable information about ancient communities and their change over time.

Base Sequence↗