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Biomedical subjects

B Andersson

Publications and source records attributed to B Andersson.

At least 271 records · Page 15Linked to original sources

Changed lateral migration of phospho-LHCII in the thylakoid membrane upon acclimation of spinach to low temperatures.

Movement of proteins along the plant thylakoid membrane is of importance for several physiological events, such as state transitions and turnover and repair of the photosystem II complex. Such lateral migrations are impaired at low temperatures, which could contribute to the increased sensitivity of plants to photoinhibitory damages at low temperatures. The migration behaviour of phospho-LHCII in thylakoid membranes isolated from cold-acclimated spinach was studied and compared to that in control membranes. The rate of migration of phospho-LHCII at low temperatures is increased 2- to 3-fold and the apparent activation energy of the migration is decreased after the cold acclimation.

Acclimatization↗

Thiotepa, busulfan, and cyclophosphamide: a new preparative regimen for autologous marrow or blood stem cell transplantation in high-risk multiple myeloma.

Forty patients with multiple myeloma received thiotepa (750 mg/m2), busulfan (10 mg/kg), and cyclophosphamide (120 mg/kg) (TBC) followed by autologous bone marrow or blood stem cell support. Granulocyte-Colony stimulating factor (G-CSF) was administered to accelerate hematopoietic recovery. Sixty-five percent of all patients responded to this treatment. Eighty-eight percent of patients transplanted in partial remission had a further reduction of the myeloma and 53% achieved a complete remission. Forty-eight percent of patients with refractory myeloma responded. All responding patients transplanted during partial remission or with primary refractory myeloma remain free of progression for a period of 4 to 24 months post-transplant, but the remission duration of patients treated in refractory relapse was short (4 months). Five of 24 patients transplanted with marrow and none of 16 receiving blood stem cells died of treatment-related complications. Use of blood stem cells resulted in more rapid granulocyte and platelet recovery. We conclude that TBC is an effective, relatively well tolerated, preparative regimen for patients with multiple myeloma.

Adult↗

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

OBJECTIVE: To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN: The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING: Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS: Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS: Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS: Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal.

Aged↗

Reduced content of the quinone acceptor QA in photosystem II complexes isolated from thylakoid membranes after prolonged photoinhibition under anaerobic conditions.

The plastoquinone content of photosystem II complexes isolated from spinach photosystem II-enriched membranes subjected to strong photoinhibitory illumination under anaerobic conditions was determined by HPLC. A pronounced decrease of the plastoquinone content was found in the photoinactivated complexes. These results corroborate earlier models in which photoinhibitory illumination is suggested to eventually lead to release of doubly reduced and protonated QA from its site on the D2-protein.

Binding Sites↗

(S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1- carbaldehyde: a new class of orally active 5-HT1A-receptor agonists.

The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n-propylamino)tetrahydronaphthalene (8-OH-DPAT). In contrast to 8-OH-DPAT, the enantiomers of compound 6 were found to have good oral availability.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Photoinhibition of Photosystem II. Inactivation, protein damage and turnover.

Even though light is the source of energy for photosynthesis, it can also be harmful to plants. Light-induced damage is targetted mainly to Photosystem II and leads to inactivation of electron transport and subsequent oxidative damage of the reaction centre, in particular to the D1 protein. Inactivation and protein damage can be induced by two different mechanisms, either from the acceptor side or from donor side of P680. The damaged D1 protein is triggered for degradation and digested by at least one serine-type proteinase that is tightly associated with the Photosystem II complex itself. The damaged Photosystem II complex dissociates from the light-harvesting antenna and migrates from appressed to non-appressed thylakoid regions where a new D1 protein is co-translationally inserted into the partially disassembled Photosystem II complex. D1 protein phosphorylation probably allows for coordinated biodegradation and biosynthesis of the D1 protein. After religation of cofactors and assembly of subunits, the repaired Photosystem II complex can again be found in the appressed membrane regions. Various protective mechanisms and an efficient repair cycle of Photosystem II allow plants to survive light stress.

Amino Acid Sequence↗

Automated sample clean-up with solid-phase extraction for the determination of aflatoxins in urine by liquid chromatography.

An automated extraction and clean-up procedure was developed for the determination of aflatoxins in human urine at the 50 pg/ml level. Aflatoxins B1, B2, G1 and G2 are captured on C2 extraction columns and simultaneously cleaned up with the aid of a robotic system. The processed samples are analysed by reversed-phase high-performance liquid chromatography. Fluorescence detection was enhanced for aflatoxins B1 and G1 using factorial design optimization of the post-column reactor. Silylation of the glass vials used in the robotic system was of the utmost importance. With non-silylated glass vials, up to 75% of the analytes were lost. Average aflatoxin recoveries were B1 95%, B2 90%, G1 93% and G2 89%.

Aflatoxins↗

Occurrence of prenylated proteins in plant cells.

In this paper evidence is presented for the occurrence of prenylated proteins in plants. When spinach leaves were incubated in the presence of [3H]mevalonate non-extractable lipids were found in the protein fraction after extraction with organic solvents. Alkaline hydrolysis liberated phytol, polyprenyl phosphates-11-15 and also, in contrast to animal cells, polyprenols-11-15. Complete removal of farnesol and geranylgeraniol required the cleavage of thioether linkages by iodomethane. The results indicate that several polyisoprenoid lipids in plant cells are covalently bound to proteins. So far a protein fraction dominated by one or more proteins in the 23 kDa region has been identified.

Chromatography, High Pressure Liquid↗

Biosynthesis of ubiquinone and plastoquinone in the endoplasmic reticulum-Golgi membranes of spinach leaves.

The localization of ubiquinone (UQ) and plastoquinone (PQ) biosynthesis in subfractions isolated from spinach leaves has been studied. UQ-9 and UQ-10 were found mainly in mitochondria, whereas PQ was enriched in chloroplasts, but also found in Golgi membranes. alpha-Unsaturated polyprenol-11 was also present at a low concentration in chloroplasts. Autoradiography revealed the presence of nonaprenyl-4-hydroxybenzoate (NPHB) and nonaprenyl-2-methylquinol (NPMQ) transferase activities involved in quinone biosynthesis in all subfractions, but the specific activities involved in quinone biosynthesis in the total microsomal fraction were 20 times higher than those in mitochondria and chloroplasts. The isolated Golgi vesicles were particularly enriched in both activities. When the incubation medium containing total microsomes or Golgi membranes was supplemented with NADH, NADPH, S-adenosylmethionine, and an ATP-generating system, NPHB and NPMQ were transferred to UQ-9 and PQ, respectively. trans-Prenyltransferase, which synthesizes the side chain of UQ and PQ, was present in the total microsomal fraction. With farnesyl-PP as substrate, no product was formed, but with geranyl-PP, solanesyl-PP was synthesized and transferred to 4-hydroxybenzoate present in the total microsomal fraction. The results show that these membranes from spinach contain farnesyl-PP synthetase. It is concluded that the plant leaf Golgi membranes contain the enzymes for both UQ and PQ biosynthesis and that a specific transport and targeting system is required for selective transfer of UQ to the mitochondria and of PQ to the chloroplast.

Cell Fractionation↗

Spectrum and outcome of congestive heart failure in a hospitalized population.

There are very few contemporary studies on the frequency and cause of congestive heart failure (CHF) in a general population. In western Sweden, inhabited by 1.64 million people, a retrospective survey was performed. All hospital records of patients with CHF, ages 16 through 65 years, were examined in all hospitals in the region. During the study period 2711 patients fulfilled the criteria for CHF or cardiomyopathy. Patients were monitored for 37 +/- 28 months. The most common cause of heart failure was coronary artery disease (IHD) (40%). Other common causes were hypertension (17%), valvular disease (13%), alcohol (11%), diabetes mellitus (10%), and systemic diseases (10%). There were positive correlations between the male sex and IHD, alcohol, and dilated cardiomyopathy; the female sex was associated with systemic diseases, valvular heart disease, and diabetes. The incidence of CHF requiring hospitalization per 100,000 in the population was 1.2 to 263 men and 1.1 to 129 women, in the youngest (age 16 to 30 years) and oldest (61 to 65 years) age groups, respectively. The 5-year survival rate was 50%. Analysis of causes performed with Cox's proportional hazards model for survival showed that age, IHD, alcohol, and diabetes were independent and powerful predictors of mortality (p < 0.001). The mode of death was progressive heart failure in 54% and sudden death in 26%. We concluded that the prognosis in patients with CHF was still very poor, even among this young population. The most common cause of CHF was IHD, and the second was hypertension.

Adolescent↗

Helicobacter pylori infection: independent risk indicator of gastric adenocarcinoma.

BACKGROUND: Helicobacter pylori has been implicated as a possible etiologic factor in gastric cancer. This case control study was performed to determine the association between H. pylori and gastric cancer, taking into account the possibility of confounding by other background factors. METHODS: Sera were collected from 112 incident case patients with gastric cancer and 103 control patients with nongastroenterological diseases, who were frequency-matched with respect to age and sex. Immunoglobulin G antibodies to H. pylori were identified using the HM-CAP immunoassay (Enteric Products Inc., Wesbury, NY). RESULTS: The prevalence of H. pylori seropositivity was significantly higher (P = 0.002) among case patients than control patients. The odds ratio (OR) was 2.60 (95% confidence interval, 1.35-5.02). The increased OR associated with H. pylori infection was confined to tumors with a noncardia location (OR, 3.06) and men (OR, 4.27). OR increased with decreasing age at cancer diagnosis to reach 9.33 in patients < 60 years of age. Multivariate logistic regression analysis was used as control for potential confounding, but the elevated OR associated with H. pylori infection remained significantly increased. CONCLUSIONS: The results support the hypothesis of H. pylori infection as an independent risk indicator of gastric cancer.

Adenocarcinoma↗

Molecular analysis of ethylene oxide-induced mutations at the HPRT locus in human diploid fibroblasts.

Ethylene oxide (EtO)-induced mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene were characterized in 28 independently derived 6-thioguanine-resistant human diploid fibroblast clones using polymerase chain reaction-based techniques and Southern blot analysis. Sequence analysis revealed one single base pair deletion and 13 base substitutions, nine of which were transversions: five AT-->TA, three GC-->TA and one GC-->CG. Four mutants were found to have GC-->AT transitions. Seven of the point mutations caused splicing errors. Six occurred in splice site sequences and one created a new splice acceptor site 16 bp upstream of exon 9. Three splice mutations were localized at the same site in the splice donor sequence of intron 8. Fourteen mutants had large HPRT gene deletions. In seven mutants the entire HPRT gene was deleted. The remaining deletion mutants had a truncated HPRT gene, where one or several exons were lost. These results show that EtO induces many different kinds of HPRT mutations, among which as many as 50% are large deletions.

Base Sequence↗

Anterior tooth replacement with implants in patients with a narrow alveolar ridge form. A clinical study using guided tissue regeneration.

Clinical and radiographic examination was used to select patients with a suspected need of guided tissue regeneration (GTR). Fifteen patients with 20 fixtures were included in the study. Nine (45%) of the fixtures were completely covered with bone at fixture surgery and no GTR was required in these cases. On the remaining 11 fixtures, one or more sites were exposed and thus an expanded polytetrafluoroethylene membrane was used. The regenerative results were assessed using 2 methods, a) calculation of exposed threads in the mouth and on projected colour slides, b) photometric evaluation of exposed area. In total, the membrane group showed a bone gain of 81% when threads were calculated. Almost complete agreement in percentage of bone gain was observed between buccal (80.7%) and lingual (82.6%) sites. Photometric evaluation for the buccal sites showed a bone gain of 74%. Complete bone regeneration (100%) was achieved when healing was free from complications and also under an exposed membrane when infection was absent. The results indicate that the membrane technique is highly successful for treatment of exposed implants when healing is free from complications. It also shows that clinical and radiographic examination is not precise enough to differentiate between those patients planned for routine fixture surgery and those with a supplementary need for GTR. Thus access to GTR technique is important when treatment is planned for borderline cases.

Adolescent↗

Proarrhythmic effects of the class III agent almokalant: importance of infusion rate, QT dispersion, and early afterdepolarisations.

OBJECTIVE: The aim was to study factors contributing to torsade de pointes in the acquired long QT syndrome. METHODS: Anaesthetised rabbits or cats were given a continuous infusion of methoxamine and the class III agent almokalant (at a rate of 5 or 25 nmol.kg-1.min-1, respectively) and the effects on incidence of torsade de pointes and QT dispersion were examined. Effects of almokalant on action potentials recorded from Purkinje fibres and ventricular cells of rabbits and cats were also studied. RESULTS: "High rate" infusion of almokalant prolonged the QTc interval [from 162(SEM 6.2) ms to 211 (5.3) ms, p < 0.001] and initiated torsade de pointes in 9/10 rabbits after a dose of 391(116.3) nmol.kg-1. During "low rate" infusion, 1/8 rabbits developed torsade de pointes (p = 0.0029) despite infusion of 900 nmol.kg-1 almokalant and QTc prolongation from 162(3.6) ms to 230(12.6) ms (p < 0.01). In eight separate rabbits given the high rate infusion of almokalant, seven developed torsade de pointes and the QTc dispersion increased from 15(1.7) ms to 32(5.6) ms (p < 0.05). In six rabbits given the low rate infusion, none developed torsade de pointes (p = 0.0023), and the QTc dispersion was unaltered. In six cats, high rate infusion induced a QT interval lengthening from 241(6.0) ms to 349(8.0) ms (p < 0.001), but in only one cat was torsade de pointes initiated and preceded by a marked increase in QT dispersion (from 22 ms to 78 ms). In vitro, almokalant caused a marked lengthening of the action potential duration and early afterdepolarisations in Purkinje fibres but not in ventricular muscle cells of the rabbit. In the cat, however, almokalant induced a homogeneous prolongation of the action potential duration in both cell types, and early afterdepolarisations were never observed. CONCLUSIONS: The rate of infusion of repolarisation delaying agents may influence the dispersion of repolarisation and play a decisive role in the initiation of torsade de pointes.

Action Potentials↗

The link between acute haemodynamic adrenergic beta-blockade and long-term effects in patients with heart failure. A study on diastolic function, heart rate and myocardial metabolism following intravenous metoprolol.

The present study was performed to find possible mechanisms linking the early effects of beta-blockade with the observed long-term effects in patients with heart failure. In 57 patients with heart failure, 13 +/- 3.1 mg of metoprolol was given intravenously. The patients were investigated by invasive haemodynamics (n = 34), including collection of myocardial metabolic data during atrial pacing stress (n = 16), by radionuclide angiography during physiological atrial pacing (n = 13), and by a bedside evaluation (n = 10). Diastolic function, measured by early peak filling rate, followed changes in heart rate, but was similar when heart rate was held constant by atrial pacing before and after beta-blockade. Following beta-blockade and slower heart rates, diastolic filling volumes were redistributed to late diastole. Metoprolol induced a parallel decrease in coronary sinus flow and myocardial oxygen consumption. Myocardial oxygen consumption following beta-blockade decreased both during spontaneous rhythm (25 +/- 15 to 16 +/- 8.8 ml min-1; P = 0.006), and during atrial pacing stress (30 +/- 13 to 23 +/- 11 ml.min-1; P = 0.004). Cardiac index decreased owing to reduction of heart rate (2.3 +/- 1.0 to 1.9 +/- 0.64 l.min-1.m2; P = 0.0003), while left ventricular filling pressure was unchanged. Ejection fraction and ventricular volumes were unaltered following atrial pacing or beta-blockade. There was a reflex increase in noradrenaline concentration after beta-blockade injection (0.96 +/- 0.66 to 1.20 +/- 0.91 nmol.l-1; P = 0.002), whereas myocardial noradrenaline overflow was unchanged. There was a trend towards an increase in myocardial lactate consumption after beta-blockade administration during atrial pacing stress. It is suggested that the surprisingly good tolerability seen after acute administration of beta-blockers to patients with severe heart failure may be explained by prolongation of the diastolic filling phase, which outweighs the negative inotropic effects. The reduced myocardial metabolic demand may allow the failing myocardium to recover and explain the excellent long-term effect on heart function following beta-blockade treatment.

Adolescent↗

Molecular spectrum of background mutation at the hprt locus in human T-lymphocytes.

The molecular basis of somatic mutation at the hypoxanthine-guanine phosphoribosyl-transferase (hprt) locus in human 6-thioguanine resistant T-cell clones from 17 individuals has been studied by Southern blot analysis, multiplex PCR (polymerase chain reaction) and direct sequencing of PCR amplified hprt cDNAs or genomic DNA. Twenty-three novel mutations were detected, which in addition to previously described mutations provide a background mutational spectrum based on a total of 45 hprt mutations in human T-cells. Twenty T-cell mutants had base substitutions in the coding region leading to 15 missense and five nonsense mutations. In addition to five frameshift mutations caused by four small deletions and one duplication, seven splice mutations, three of them with skipping of exon 8, were detected. Thirteen genomic structural alterations have also been identified; one of these had a genomic exon 1 deletion with a GGCCGG-hexamer in both breakpoints.

Adult↗