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Biomedical subjects

U Lundberg

Publications and source records attributed to U Lundberg.

At least 55 records · Page 3Linked to original sources

In vivo and in vitro identity of site specific cleavages in the 5' non-coding region of ompA and bla mRNA in Escherichia coli.

The bla and ompA gene transcripts were used as substrates to probe Escherichia coli extracts for ribonucleolytic activities. A site specific endoribonucleolytic activity was identified that cleaves ompA and bla mRNA. The cleavages occur in vitro and in vivo. For both the bla and ompA mRNA most of the cleavage sites which were identified map in the 5' non-coding region. The cleavages of the ompA transcript have been previously suggested to regulate the growth rate dependent stability of this mRNA. Thus we propose that the identified endoribonucleolytic activity may be involved in the degradation of mRNA. Analysis of mutants revealed that the cleavages are mediated by endonucleases which do not seem to be identical to RNase III, RNase E or RNase P.

Bacterial Outer Membrane Proteins↗

Urinary catecholamines: comparison between HPLC with electrochemical detection and fluorophotometric assay.

Comparisons between catecholamines determined by HPLC (with electrochemical detection) and fluorometry in urine samples from healthy adults and children, respectively, showed high correlations. In agreement with greater specificity for HPLC, mean values were higher for the fluorometric assay. However, it was concluded that fluorometric assays provide as valid and sensitive indices of stress-induced changes in catecholamine excretion in humans as HPLC.

Adult↗

Effects of cadmium on canine renal cortical adenylate cyclase.

The present studies examine the effects of cadmium (Cd2+) on adenylate cyclase activity in basolateral renal cortical membranes from normal dogs. Cd2+, in the dose range of 1 to 200 microM caused a dose-dependent inhibition of adenylate cyclase activity due to competitive inhibition with respect to the allosteric activator Mg2+ (increase in the Kact for Mg2+ from 13.8 to 37.2 mM). In addition, increasing Cd2+ concentrations from 0 to 25 microM resulted in a purely competitive inhibition with respect to ATP. The Km for ATP increased from 61 to 128 microM. When Mn2+ at a concentration of 20 mM was substituted for Mg2+, Cd2+ maintained its inhibitory effect at concentrations lower than 25 microM. At higher concentrations it stimulated enzyme activity in a dose-dependent fashion. In the absence of other divalent cations Cd2+ was a potent stimulator of basal adenylate cyclase activity, far more potent than the physiological activator of the system Mg2+. Kact for Cd2+ was 1.0 mM (Kact for Mg2+ 20 mM), whereas the Vmax showed a fourfold increase compared with the Mg2+-stimulated membranes. However, under these conditions, synthetic bovine parathyroid hormone (1-34) or 5'-guanylylimidodiphosphate did not stimulate adenylate cyclase. It is concluded that Cd2+ behaves as a partial agonist in this system, due to its ability to form a new enzymatic substrate complex: Cd-ATP, which competes with the physiological substrate Mg-ATP at the catalytic site of the enzyme. In addition, Cd2+ in the absence of other divalent cation stimulates basal enzyme activity, presumably through interaction at an additional site, closely related to the allosteric metal regulatory site of this enzyme system.

Adenylyl Cyclases↗

Urinary monoamine metabolites as indices of mental stress in healthy males and females.

Concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), the dopamine metabolite homovanillic acid (HVA) and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl glycol (HMPG) were determined in urine samples from healthy male and female students by mass fragmentography. Urine samples were obtained after a demanding examination (mental stress) and a day of ordinary school work (control condition). Self-ratings were obtained of feelings induced by the examination, and of habitual psychosomatic symptoms. The results for both sexes showed that the examination stress induced a significant increase of HVA and HMPG excretion, but not of 5-HIAA. The males excreted significantly more of each of the metabolites than the females. The pattern of correlations between metabolite levels and psychological and psychosomatic variables were strikingly different for the two sexes.

Adolescent↗

Appearance of an arachidonic acid 15-lipoxygenase pathway upon differentiation of the human promyelocytic cell-line HL-60.

The metabolism of arachidonic acid and 15-HPETE was studied in a human promyelocytic cell line (HL-60). Upon exposure to DMSO, HL-60 cells undergo differentiation and acquire a 15-lipoxygenase activity while undifferentiated cells challenged with either arachidonic acid or 15-HPETE did not enzymatically transform these precursors. Products of the arachidonic acid 15-lipoxygenase pathway were identified by HPLC. UV-absorption and gas chromatography-mass spectrometry. Results indicate that upon differentiation HL-60 cells express a 15-lipoxygenase activity as well as the ability to transform 15-HPETE to 8,15-DHETEs and 14,15-DHETE. Moreover, these findings suggest that products of the 15-lipoxygenase cascade may be generated by a single cell system.

Arachidonate Lipoxygenases↗

Stereochemistry, total synthesis, and biological activity of 14,15-dihydroxy-5,8,10,12-eicosatetraenoic acid.

The stereochemistry of the major isomer of 14,15-dihydroxy-5,8,10,12-eicosatetraenoic acid formed from 15-hydroperoxyeicosatetraenoic acid in human leukocytes was determined. The structure (erythro-14(R),15(S]-14,15-dihydroxy-5,8-cis-10,12-trans-eicosatetraenoi c acid) was assigned based on sodium arsenite thin-layer chromatography, NMR spectroscopy, and comparison with material prepared by total synthesis. This compound was found to inhibit leukotriene B4-induced superoxide anion generation in human neutrophils (IC50 = 10(-8)-10(-7) M). Superoxide anion generation induced by either formylmethionyl-leucyl-phenylalanine or arachidonic acid was not affected.

Arachidonic Acid↗

Formation of leukotriene C4 by human leukocytes exposed to monosodium urate crystals.

Monosodium urate (MSU) crystals stimulate the metabolism of arachidonic acid in mixed populations of human leukocytes. Leukocytes exposed to MSU crystals released leukotriene C4. Leukotriene C4 (LTC4) was characterized and detected by high-performance liquid chromatography (HPLC), UV absorption, bioassay with guinea pig ileum, and radioimmunoassay. Results indicate that MSU crystals stimulate the transformation of arachidonic acid and the formation of leukotriene C4 in human leukocytes; an effect inhibited by colchicine. Moreover, they suggest that LTC4 may serve as a mediator of inflammation in crystal-associated diseases.

Chromatography, High Pressure Liquid↗

Formation of leukotrienes and hydroxy acids by human neutrophils and platelets exposed to monosodium urate.

Monosodium urate (MSU) crystals stimulate the production of arachidonic acid metabolites by human neutrophils and platelets. Neutrophils exposed to MSU generated leukotriene B (LTB), 6-trans-LTB4, 12-epi-6-trans-LTB4, and 5S, 12S DHETE from endogenous sources of arachidonate. In addition to these metabolites both monohydroxyeicosatetraenoic acids (i.e., 5-HETE) and omega-oxidation products (i.e., 2O -COOH LTB4) were formed by neutrophils exposed to MSU. Addition of exogenous arachidonic acid led to increased formation of each of these metabolites. When neutrophils were treated with colchicine (10 microM), LTB4 but not 5-HETE formation was impaired. (1-14C)Arachidonate-labeled platelets exposed to MSU released (1-14C)-arachidonate, (14C)-12 HETE, (14C)-HHT and (14C)-thromboxane B2. Results indicate that MSU stimulates arachidonic acid metabolism in both human neutrophils and platelets. Moreover, they suggest not only that metabolites of arachidonate may be considered as possible candidates for mediators of inflammation in crystal-associated diseases, but that colchicine blocks the formation of LTB4.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Inhibition of human natural killer cell activity by (14R,15S)-14,15-dihydroxy-5Z,8Z,10E,12E- icosatetraenoic acid.

The interactions between products of the 15-lipoxygenase cascade and human natural killer (NK) cell activity have been studied. Addition of human leukocyte-derived (14R,15S)-14,15-dihydroxy-5Z,8Z,10E,12E-ic osatetraenoic acid (14,15-DiHETE) to the NK cytotoxicity assay against K562 target cells resulted in inhibition of NK cell activity, whereas addition of other 15-lipoxygenase-associated metabolites [i.e., (15S)-15-hydroperoxy-5Z,8Z,11Z,13E-icosatetra eno ic acid, (15S)-15-hydroxy-5Z,8Z,11Z,13E-icosatetraenoic acid, and (8R,15S)- and (8S,15S)-8,15-dihydroxy-5Z,9E,-11E,13E-icosat etr aenoic acid isomers] resulted in little or no inhibition of NK function. Dose-response studies indicate that leukocyte-derived 14,15-DiHETE and 14,15-DiHETE methyl ester, at micromolar concentrations, inhibit NK function even in the presence of 2.5% fetal calf serum. Synthetic 14,15-DiHETE prepared by total organic synthesis displayed similar biological activities over identical dose ranges. These icosanoids do not inhibit NK target cell binding and they exert only a variable effect in either antibody-dependent cytotoxicity or cytotoxic T-lymphocyte assays. These results demonstrate that the 14,15-DiHETE inhibits NK cell function in vitro. Moreover, they suggest that activation of the 15-lipoxygenase cascade and formation of 14,15-DiHETE in vivo may provide a mode of immune regulation.

Antibody-Dependent Cell Cytotoxicity↗

Note on Type A behavior and cardiovascular responses to challenge in 3-6-yr old children.

Using the MYTH-scale [1], the antecedents of Type A behavior were studied in fifteen healthy 3-6-yr old boys. Boys with scores above ('Type A') and below ('Type B') the median were compared in terms of systolic and diastolic blood pressure and heart rate during rest, and during 'emotional' and 'physical' challenge. It was found that 'Type A boys' responded to challenge with a greater increase in systolic blood pressure than 'Type B boys' (significant during physical challenge), while there were no differences during the rest condition. Diastolic blood pressure and heart rate did not differ markedly between the groups.

Arousal↗

Consistency in catecholamine and cortisol excretion in males and females.

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.

Adolescent↗

Psychophysiological stress responses in postmenopausal women before and after hormonal replacement therapy.

Seventeen females with a history of hot flushes, perspiration, and amenorrhea of at least 6 months' duration, and a serum FSH level exceeding 40 IU/l entered a cyclic treatment with 17 beta-estradiol and estriol combined with norethsterone (Trisekvens, Novo). Each patient took part in three experimental sessions, six weeks apart, in which stress was induced by mental performance tests. To permit separation of treatment and habituation effects the patients were randomly assigned to one of two groups, Group 1 starting therapy after the first, Group 2 after the second session. Treatment eliminated hot flushes and perspiration and reduced serum FSH levels without causing changes in blood pressure or heart rate. There was no correlation between hormonal treatment and excretion of catecholamines during stress. Testosterone and androstenedione serum levels remained unchanged during therapy. Self-reports showed that tiredness, headache, tension and anxiety were significantly reduced following treatment.

Adult↗