The dynamic photosynthetic membrane and regulation of solar energy conversion.
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Cell Membrane↗
Biomedical subjects
B Andersson
Publications and source records attributed to B Andersson.
N,N-Dialkylated monophenolic trans-2-phenylcyclopropylamines: novel central 5-hydroxytryptamine receptor agonists.
N,N-Dialkylated monophenolic derivatives of trans-2-phenylcyclopropylamine were synthesized and tested for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor stimulating activity by use of a biochemical test method in rats. A hydroxy substituent in the 2- or 3-position of the phenyl ring was required for 5-HT-receptor stimulation. N,N-Diethyl or N,N-di-n-propyl substitution gave the most potent 5-HT-receptor agonists. The 4-hydroxy and 3,4-dihydroxy derivatives of trans-2-phenyl-N,N-di-n-propylcyclopropylamine were inactive at central DA and 5-HT receptors. In contrast, the corresponding 3-hydroxy derivative 18 and some of its derivatives weakly affected both DA and NE synthesis. Two of the most potent 5-HT-receptor agonists, trans-2-(2-hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (8) and the 3-hydroxy isomer 18 were resolved into the enantiomers. The 1R,2S enantiomers of 8 and 18 displayed 5-HT activity, while the 1S,2R enantiomers were inactive. Compound (1R,2S)-18, but not (1R,2S)-8, weakly affected rat brain DA and NE synthesis.
Alkylation↗
Occurrence and pharmacological significance of metabolic ortho-hydroxylation of 5- and 8-hydroxy-2-(di-n-propylamino)tetralin.
Aromatic ortho-hydroxylation in the liver might be one of several possible reasons for the low bioavailabilities of the potent, centrally acting dopaminergic and serotoninergic agonists 5- and 8-hydroxy-2-(di-n-propylamino)tetralin, respectively. In vitro and in vivo experiments showed that such an oxidative metabolism did indeed take place. However, the amount of hydroxylated metabolites found in the brain was estimated to represent only 0.3% of the total amount of drug administered. The O-methylation rates of these catechols were also measured in vitro and showed that 5,6-dihydroxy-2-(di-n-propylamino)tetralin is a poor substrate for catechol O-methyltransferase (COMT) and that its 7,8-dihydroxy isomer is virtually devoid of substrate activity. No O-methylated metabolites were detected in the in vivo samples analyzed. A new synthetic strategy was applied to achieve the isomeric catechols studied. 5-Methoxy- or 8-methoxy-2-(di-n-propylamino)tetralin was lithiated in the ortho position and the metalated species was subsequently quenched in nitrobenzene, yielding the methoxy hydroxy isomers, which were heated in 48% aqueous HBr to achieve the corresponding catechols.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Role of adherence of Streptococcus pneumoniae in acute otitis media.
The adherence of Streptococcus pneumoniae to human nasopharyngeal epithelial cells was studied as a possible determinant in the development of acute otitis media (AOM). Pneumococcal isolates were obtained from the nasopharynx (NP) and middle ear fluid of infants followed from birth in a prospective study of pneumococcal carriage and infection. The adherence of 33 middle ear fluid isolates from 19 infants with AOM was compared with 143 strains recovered from NP cultures taken from each child both at the time of their acute infections and on other occasions. We studied 171 NP isolates from 29 "carrier" infants, who had no pneumococcal infections, for comparison. Adherence properties were not associated with any particular pneumococcal capsular types, nor were adherent strains more frequent among infants with AOM. There was no evidence to support the hypothesis that pneumococci associated with AOM have a special propensity for adherence. Adherence was a frequent characteristic of pneumococci recovered from the NP, especially in connection with upper respiratory tract infection, and may be required for the establishment of colonization but was not a property that discriminated between carriage strains and those causing AOM.
Bacterial Adhesion↗
On the presence of a nicotinamide nucleotide transhydrogenase in mitochondria from potato tuber.
Mitochondria isolated from potato (Solanum tuberosum L.) tuber were investigated for the presence of a nicotinamide nucleotide transhydrogenase activity. Submitochondrial particles derived from these mitochondria by sonication catalyzed a reduction of NAD(+) or 3-acetylpyridine-NAD(+) by NADPH, which showed a maximum of about 50 to 150 nanomoles/minute.milligram protein at pH 5 to 6. The K(m) values for 3-acetylpyridine-NAD(+) and NADPH were about 24 and 55 micromolar, respectively. Intact mitochondria showed a negligible activity in the absence of detergents. However, in the presence of detergents the specific activity approached about 30% of that seen with submitochondrial particles. The potato mitochondria transhydrogenase activity was sensitive to trypsin and phenylarsine oxide, both agents that are known to inhibit the mammalian transhydrogenase. Antibodies raised against rat liver transhydrogenase crossreacted with two peptides in potato tuber mitochondrial membranes with a molecular mass of 100 to 115 kilodaltons. The observed transhydrogenase activities may be due to an unspecific activity of dehydrogenases and/or to a genuine transhydrogenase. The activity contributions by NADH dehydrogenases and transhydrogenase to the total transhydrogenase activity were investigated by determining their relative sensitivities to trypsin. It is concluded that, at high or neutral pH, the observed transhydrogenase activity in potato tuber submitochondrial particles is due to the presence of a genuine and specific high molecular weight transhydrogenase. At low pH an unspecific reaction of an NADH dehydrogenase with NADPH contributes to the total trans-hydrogenase activity.
Journal Article↗
Acute effects of short-term fasting on blood pressure, circulating noradrenaline and efferent sympathetic nerve activity.
Eleven moderately obese women, aged 46-62 years, with a body mass index of 29-34 and with borderline hypertension (repeated diastolic blood pressure greater than 90 mmHg) fasted for 48 hours. Before the fast and after 48 hours of fasting, plasma noradrenaline, urinary noradrenaline, urine potassium, urine sodium and weight were measured. In six of the patients muscle nerve sympathetic activity was recorded from the peroneal nerve by tungsten microelectrodes for 15 min each time. The efferent muscle sympathetic activity (MSA) was expressed as the number of bursts/min. The recordings were done before the fast and after 48 hours of fasting. We found significant decreases in body weight from 88.4 +/- 2.5 kg to 86.4 +/- 2.5 kg. Systolic blood pressure (BP) was reduced from 158 +/- 3 mmHg to 146 +/- 5 mmHg (p less than 0.001) and diastolic BP from 96 +/- 3 mmHg to 89 +/- 3 mmHg (p less than 0.01) during the fast. MSA was significantly increased from 42.0 +/- 5.5 bursts/min to 44.5 +/- 5.8 (n = 6), while plasma and urine noradrenaline concentrations (n = 11) showed a non-significant tendency to increase. We conclude that the hypotensive response during the first days of extensive caloric reduction is not due to a decreased sympathetic activity. If anything, there may be weak increase of efferent sympathetic nerve activity and venous plasma levels of circulating noradrenaline. The mechanisms behind the acute hypotensive response to negative caloric balance are thus still unclear, but obviously different from long-term adaptation of the blood pressure.
Blood Pressure↗
Effect of terfenadine and placebo on symptoms after nasal allergen provocation.
Terfenadine (60 mg b.i.d.) was compared with placebo in a randomized, double-blind, cross-over study in twenty-three patients with birch pollen allergy. The patients were treated during two 7-day periods separated by a 2-week wash-out period during a season free from birch pollen. Nasal provocations with birch pollen extracts were made at study entry and after each treatment period. Blockage (rhinomanometry), secretion (weight) and sneezings (number) were compared between treatments. The results showed a significant inhibitory effect of terfenadine on secretion and sneezing, but no significant difference between treatments with regard to blockage. Terfenadine showed no signs of sedative properties or inhibition of salivation.
Adult↗
Role of attachment for the virulence of Streptococcus pneumoniae.
Adherence of microorganisms to mucosal surfaces is a general phenomenon among microorganisms infecting the human host. Its role for persistence and colonization as well as production of local inflammation is well established. This paper describes the adhesion of Streptococcus pneumoniae to human epithelial cells. Strains from various anatomical sites or diseases are compared for attaching capacity. Isolates from the same host but at different times are also compared. The molecular mechanisms, the so-called adhesin-receptor interactions, are partially described. The pneumococcus recognizes a sugar sequence; GlcNAc beta 1-3Gal; on the surface of the host epithelial cell. Glycoconjugates containing this disaccharide act as receptors for adhering pneumococci. The adhesin in pneumococcal attachment is less well characterized. It is a heat and trypsin sensitive component, most likely a peptide, which forms a bridge between the receptor and an anchoring site in the pneumococcal cell wall. Receptor active saccharides are part of the adhesion-inhibitory activity found in human milk.
Bacterial Adhesion↗
Expression of ABH blood group isoantigen as a prognostic factor in transitional cell bladder carcinoma.
The expression of ABH blood group isoantigen was determined with the avidin-biotin-peroxidase complex method in a retrospective consecutive material of 230 patients with transitional cell bladder carcinoma. The follow-up period was 5 to 9 years. The five-year corrected survival for 65 patients whose primary tumours showed predominant expression of ABH antigens ('positive') was 80% and for 146 patients with predominant deletion ('negative') 60% (p less than 0.01). Of 107 patients with superficial tumours there were 60 negative and 47 positive. In an analysis of early progression, the negative tumours were found to progress more frequently than positive ones (p less than 0.03). Twenty-three per cent of the negative tumours finally progressed during the whole follow-up, compared with 15% of the positive ones; this difference was not significant. Almost all progressing tumours became negative when they reached an advanced stage.
ABO Blood-Group System↗
Mechanisms of pneumococcal attachment.
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Bacterial Adhesion↗
Bacterial adherence in urinary and respiratory tract infection.
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Bacterial Adhesion↗
Tumor necrosis factor and human hematopoiesis: II. Inhibition and mode of action on normal and chronic myelogenous leukemia-derived granulocyte-macrophage progenitor cells.
Recombinant technology-produced tumor necrosis factor alpha (rTNF-alpha) inhibits clonogenic growth of normal granulocyte-macrophage colony-forming cells (GM-CFC) when it is continuously present in the culture medium. In our studies, day 7 and day 14 GM-CFC were inhibited and showed similar response. A decrease in the number of large colonies accounted for most of the inhibition, whereas growth of small clusters was inhibited to a lesser extent. Comparable inhibition was observed when bone marrow cells were cloned at low (2.5 x 10(4)/ml) or high (10 x 10(4)/ml) cell densities. A similar degree of inhibition by rTNF-alpha was found when conditioned medium from the human placenta or a bladder carcinoma cell line was used as the source of the colony-stimulating factors (CSF). The dose-response curve of GM-CFC to rTNF-alpha was sigmoidal, the maximum inhibition (90%) occurring at approximately 100 ng/ml of rTNF-alpha. Short-term treatment of bone marrow in suspension culture for 2 hr did not affect the subsequent colony formation, suggesting that TNF had an antiproliferative rather than a direct toxic effect on normal GM-CFC. GM-CFC derived from previously untreated patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) showed an in vitro dose response to rTNF-alpha similar to that of normal GM-CFC. Inhibition of colony formation by CML-derived GM-CFC was more pronounced than GM-CFC from normal marrows, especially at low concentrations of rTNF-alpha. An increase in the concentration of rTNF-alpha above 250 ng/ml had no further effect on colony formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone Marrow Cells↗
Detection of leukemic clone maturation in vivo by premature chromosome condensation.
The purpose of this study was to determine the feasibility of using the technique of premature chromosome condensation to detect the in vivo maturation of abnormal elements in patients with chronic myelogenous leukemia (CML), myelodysplastic syndrome, and acute leukemia. Patients were chosen for study if there were a clinical suggestion of in vivo maturation and a leukemic clone exhibiting a distinguishable karyotypic abnormality. Mature peripheral blood granulocytes were enriched by two-step Ficoll-Hypaque gradient sedimentation and fused with mitotic Chinese hamster ovary cells to induce the formation of prematurely condensed chromosomes (PCC). These PCC were then analyzed for chromosome number per cell (in the case of patients with a numerical abnormality) or by G-banding (in the case of specific translocations). Of 13 patients chosen for study, 12 showed karyotypic evidence for maturation of the abnormal elements in vivo. Maturation was observed in a number of clinical situations including before treatment in benign CML and myelodysplasia, after low-dose and high-dose chemotherapy in myelodysplasia and acute myelogenous leukemia (AML), and in remission. These results suggest that the technique of premature chromosome condensation can be a powerful tool in better understanding the biology of disease and mode of response to therapy in vivo in patients with leukemia and preleukemic syndromes, especially during treatment with agents thought to induce maturation of the leukemic elements.
Aneuploidy↗
Determination of specific mercapturic acids in human urine after experimental exposure to toluene or o-xylene.
Volunteers were exposed to toluene and o-xylene for 4 h at 300 mg/m3 and 350 mg/m3, respectively, in an exposure chamber. Urine voided during and after the exposure was analysed for S-benzyl-N-acetylcysteine (toluene mercapturic acid) and S-(o-methylbenzyl)-N-acetylcysteine (o-xylene mercapturic acid). The amount of S-(o-methylbenzyl)-N-acetylcysteine found in urine after exposure corresponded to a metabolic yield of less than about 0.01% of the total uptake. No S-benzyl-N-acetylcysteine was found. Thus, determination of specific mercapturic acids after exposure to toluene or o-xylene can hardly be used for genotoxic monitoring.
Acetylcysteine↗
Heterogeneity in acute undifferentiated leukemia.
From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.
Acute Disease↗
Lipid composition of plasma membranes isolated from light-grown barley (Hordeum vulgare) leaves: identification of cerebroside as a major component.
The total lipid composition of highly purified plasma membranes from light-grown barley (Hordeum vulgare) leaves was investigated. The plasma membranes were separated from intracellular membranes by subfractionation of the microsomal fraction using aqueous polymer two-phase partitioning. A novel finding was that glucocerebroside was a major lipid of the plasma membrane (23 mol%). The most abundant lipid class in the plasma membrane was phospholipid (42 mol%), consisting mainly of phosphatidylcholine and phosphatidylethanolamine, together with free sterols at a level of 28 mol%. The only free sterols of the plasma membrane were campesterol (15%), stigmasterol (23%), and sitosterol (62%). The plasma membrane contained a relatively high proportion of saturated fatty acids compared to the bulk of intracellular membranes, the major components of the plasma membrane being palmitic (16:0), linoleic (18:2), and linolenic (18:3) acids in approximately equal amounts.
Cell Membrane↗
Molecular characteristics of chronic myelogenous leukemia in blast crisis.
We have studied the expression of c-abl and c-myc in leukemic cells of patients in all clinical phases of chronic myelogenous leukemia. We demonstrate that an aberrant 8-Kb c-abl related transcript is present in the RNA of the leukemic cell from all patients with Ph+ CML and that the loss of both normal chromosome #9 is associated with the loss of the normal c-abl related transcripts. This represents direct evidence that the normal c-abl related transcripts derive from the normal c-abl gene locus on the normal chromosome #9, while the aberrant c-abl related transcript in Ph+ CML derives from the hybrid bcr-abl gene formed as a result of the t(9;22). We further demonstrate that trisomy 8 in some instances is associated with enhanced expression of the c-myc oncogene.
Blast Crisis↗
Resolved cis-10-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b- octahydrobenzo[f]quinoline : central serotonin stimulating properties.
cis-10-Hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b -octahydrobenzo[f]quinoline (4) is a centrally acting serotonin (5-HT) receptor agonist of moderate potency. Due to its semirigid character and the obvious similarity between (4aR,10bS)-4 and more potent, centrally acting 5-HT receptor agonist cis-(1S,2R)-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (2), we carried out the preparation (via resolution of 6, a precursor of 4) and the pharmacological testing of the enantiomers of 4. We were able to show that the active enantiomers of 4 and 2 coincide in terms of stereochemistry, i.e., that it is the 4aR,10bS enantiomer of 4 that is the more active one. The absolute configuration was assigned on the basis of single-crystal X-ray analysis of the precursor (+)-6 of the active enantiomer (-)-4. Conformational analysis with molecular mechanics (MM2) calculations were performed on the N-methyl analogues of compounds cis-(1S,2R)-2 (cis-(1S,2R)-3) and cis-(4aR,10bS)-4 (cis-(4aR,10bS)-7). Both ammonium and free amine forms were subjected to these calculations. The results show a preference for the N-equatorial conformation, which is corroborated by the X-ray structure of (+)-6.HCl. The relatively low potency of compound cis-(4aR,10bS)-4 might be explained by unfavorable direction of the N-lone pair (or ammonium hydrogen) bond in this compound as compared to cis-(1S,2R)-2 and trans-(4aR,10bR)-5, which can be predicted to be the more active enantiomer of compound 5.
Animals↗