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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 289 records · Page 16Linked to original sources
PubMed1989

Postantibiotic and bactericidal effect of imipenem against Pseudomonas aeruginosa.

The postantibiotic effect of imipenem on Pseudomonas aeruginosa was studied at different inocula using one ATCC strain and four clinical isolates. The postantibiotic effect was measured using two different methods: viable counts and bioluminescence assay of intracellular bacterial ATP. The postantibiotic effect could be demonstrated with both methods (viable counts 1-2 h, ATP assay 3-5 h) for all strains at an inoculum of 10(6) CFU/ml. When the inoculum was raised to 10(8) CFU/ml, no postantibiotic effect could be observed with either method using routine growth conditions. This disappearance of the postantibiotic effect coincided with a loss of bactericidal effect of imipenem when high inocula were used. Improved oxygenation of the cultures restored the bactericidal and postantibiotic effects of imipenem at high inocula.

Dose-Response Relationship, Drug↗
PubMed1989

Technical and clinical aspects of ultrasound guided oocyte recovery.

In our experience, as well as that of many other IVF groups, transvaginal, ultrasound-guided follicle aspiration is less invasive and comparable to, or better than laparoscopy with regard to the efficiency of oocyte recovery and safety. For these reasons, we believe that ultrasound-guided follicle aspiration will gradually become the method of choice if the only purpose is to retrieve oocytes.

Female↗
PubMed1989

The new selective D2-dopamine receptor antagonist raclopride--pharmacokinetics, safety and tolerability in healthy males.

Raclopride, a new potential antipsychotic drug, with high selectivity and affinity for central D2-dopamine receptors, was in this first human study administered to 8 healthy male volunteers in single oral doses from 0.1 to 16 mg. Two subjects, known to be slow metabolizers of debrisoquine, were also included. Pharmacokinetics, safety, tolerability, and effect on plasma prolactin levels were evaluated. The maximum plasma concentrations of raclopride (Cmax) and the area under the raclopride curve vs time (AUC) increased proportionally with dose. No deviant kinetic parameters were seen in the slow debrisoquine metabolizers. Only minor deviations in biochemical and physiological safety parameters were found. Raclopride was well tolerated by all subjects at doses up to 8 mg but not at 16 mg because of akathisia. No other extrapyramidal side-effects were recorded. The drug induced a rapid and transient increase of plasma prolactin concentrations.

Administration, Oral↗
PubMed1988

The elongation factor EF-Tu from E. coli binds to the upstream activator region of the tRNA-tufB operon.

The polypeptide chain elongation factor EF-Tu of Escherichia coli is encoded by two genes, tufA and tufB, located in two different operons. Experiments in which either tufA or tufB was inactivated demonstrated that expression of the tRNA-tufB operon is dependent on a functioning tufA and thus on EF-Tu (1, to be published). In order to study a possible role of EF-Tu as trans-activator of the tRNA-tufB operon, we have investigated in vitro binding of an EF-Tu. GDP preparation to various DNA fragments of the operon. We demonstrate that specific binding occurs to a cis-acting region delimited from position -134 to the promoter, previously shown to enhance tufB transcription. Electrophoretic retardation assays reveal the formation of maximally three protein/DNA complexes, indicating that more than one protein molecule can bind to the DNA. The EF-Tu preparation used was obtained by affinity chromatography and appeared to be 95% pure. It lost its DNA binding activity upon further purification. That EF-Tu is nonetheless involved in the DNA binding is suggested by the observation that none of the three complexes is formed in the presence of kirromycin, an antibiotic that binds EF-Tu with high specificity. If so, EF-Tu.GDP most likely binds to the activator region of the tRNA-tufB operon in combination with another non-identified protein or component.

DNA, Bacterial↗
PubMed1988

Mitochondrial targeting sequences. Why 'non-amphiphilic' peptides may still be amphiphilic.

The notion that mitochondrial targeting peptides form amphiphilic alpha-helices with one apolar and one polar, positively charged face is controversial, since some experimental results seem to imply that non-amphiphilic targeting peptides can also function as import signals. However, the standard methods used to assess the amphiphilicity of a peptide may be misleading, since they do not take the flexibility of the amino acid side chains into account. To demonstrate this, we have developed a new method for calculating the amphiphilicity of helical peptides.

Amino Acid Sequence↗
PubMed1988

Molecular dynamics simulations of ribonuclease T1: analysis of the effect of solvent on the structure, fluctuations, and active site of the free enzyme.

Molecular dynamics simulations were performed on ribonuclease T1 (RNase T1; EC 3.1.27.3) to determine a structure for the free enzyme. Simulations starting with the X-ray coordinates for the 2'GMP-RNase T1 complex were done in vacuo and with an 18-A water ball around the active site using stochastic boundary conditions to understand the influence of water on both the structure and fluctuations of the enzyme. Removal of 2'GMP caused structural changes in the loop regions, including those directly interacting with the bound inhibitor in the crystal structure, while regions of secondary structure were less affected. The presence of solvent in the simulation damped the structural changes observed, which may be related to the use of full charges in both simulations. Fluctuations were also affected by the water, which generally increased both at the surface and in the interior of the protein. The active site in vacuo collapsed upon itself, forming a number of protein-protein hydrogen bonds leading to larger structural changes and lowered fluctuations while the presence of water kept the active site open, minimized structural changes, and increased fluctuations. Such fluctuations in the active site may be important for the binding of inhibitors or substrates to the enzyme. Lastly, results from the water simulation allow the prediction of a motion for a hypothetical tryptophan at position 45, which can ultimately be tested experimentally via time-resolved fluorescence using a site-specific mutant of the enzyme.

Aspergillus oryzae↗
PubMed1988

Insulin-like growth factor 1 stimulates the release of acetylcholine from rat cortical slices.

The effect of somatomedin, or insulin-like growth factors (IGF-1 and IGF-2), on the basal and potassium induced release of [3H]acetylcholine ([3H]Ach) from rat cortical slices, previously preincubated with [3H]choline ([3H]Ch), was studied in vitro. IGF-1 (1.4 x 10(-9) to 1.4 x 10(-8) M) had no effect on the basal release of [3H]ACh, while IGF-1 (1.4 x 10(-9) to 4.3 x 10(-8) M) increased the potassium induced release of [3H]ACh from rat brain slices in a concentration-dependent manner. However IGF-2 (1.4 x 10(-8) M) had no effect. Insulin (1.8 x 10(-8) to 5.3 x 10(-8) M), similarly, did not have any influence on the release of [3H]ACh, demonstrating that the facilitatory effect of IGF-1 on [3H]ACh release is not mediated via insulin receptors. This report demonstrates for the first time that IGF-1 has an effect on neurotransmission in the adult brain.

Acetylcholine↗
PubMed1988

Structural and functional studies of the interaction of the eukaryotic elongation factor EF-2 with GTP and ribosomes.

The structure of the guanosine nucleotide binding site of EF-2 was studied by affinity labelling with the GTP analogue, oxidized GTP (oGTP), and by amino acid sequencing of polypeptides generated after partial degradation with trypsin and N-chlorosuccinimide. Native EF-2 contains two exposed trypsin-sensitive cleavage sites. One site is at Arg66 with a second site at Lys571/Lys572. oGTP was covalently bound to the factor between Arg66 and Lys571. After further cleavage of this fragment with the tryptophan-specific cleavage reagent N-chlorosuccinimide, oGTP was found associated with a polypeptide fragment originating from a cleavage at Trp261 and Trp343. The covalent oGTP . EF-2 complex was capable of forming a high-affinity complex with ribosomes, indicating that oGTP, in this respect, induced a conformation in EF-2 indistinguishable from that produced by GTP. Although GTP could be substituted by non-covalently linked oGTP in the factor and ribosome-dependent GTPase reaction, the factor was unable to utilize the covalently bound oGTP as a substrate. This indicates that the conformational flexibility in EF-2 required for the ribosomal activation of the GTPase was inhibited by the covalent attachment of the nucleotide to the factor. EF-2 cleaved at Arg66 were unable to form the high-affinity complex with ribosomes while retaining the ability to form the low-affinity complex and to hydrolyse GTP. The second cleavage at Lys571/Lys572 was accompanied by a total loss of both the low-affinity binding and the GTPase activity.

Affinity Labels↗
PubMed1988

Stereoselective binding of 11C-raclopride in living human brain--a search for extrastriatal central D2-dopamine receptors by PET.

The selective D2-dopamine receptor antagonist raclopride and its pharmacologically inactive (R)-enantiomer FLB472 were labelled with 11C and used in a study with positron emission tomography to examine the stereoselectivity of 11C-raclopride binding to central D2-dopamine receptors in three healthy men. After the injection of 11C-raclopride, there was a high accumulation of radioactivity in the dopamine-rich basal ganglia, whereas after the injection of 11C-FLB472 there was no such accumulation of radioactivity. Thus, the binding of 11C-raclopride is stereoselective. Distribution ratios [radioactivity in a brain region/"free" (not protein-bound) radioactivity in plasma] were calculated for the two enantiomers to study regional differences in the accumulation of radioactivity. The distribution ratios in white matter were similar for the two enantiomers. In the putamen, a three to four-fold higher distribution ratio was found for 11C-raclopride than for 11C-FLB472, reflecting the presence of specific binding of 11C-raclopride binding to D2-dopamine receptors in the basal ganglia. In the temporal and frontal cortices the distribution ratios were, however, only a few per cent higher for 11C-raclopride than for 11C-FLB472, indicating that if D2-dopamine receptors are present in the human neocortex, then their density is indeed very low.

Adult↗
PubMed1988

Molecular dynamics simulations of ribonuclease T1. Effect of solvent on the interaction with 2'GMP.

Molecular dynamics simulations in vacuum and with a water sphere around the active site were performed on the 2'GMP-RNase T1 complex. The presence of water led to the maintenance of the 2'-GMP-RNase T1 interactions as compared to the X-ray structure, including the hydrogen bonds implicated in the enzyme-inhibitor recognition process. The sidechain of His92 in the molecular dynamics water simulation, however, hydrogen bonds directly to the phosphate of 2'GMP in contrast to the X-ray structure but in support of the role of that residue in the enzyme's catalytic mechanism. Fluctuations of active-site residues are not strongly influenced by water, possibly owing to the exclusion of water by the bound 2'GMP, which did show an increase in mobility. Analysis of the 2'GMP-RNase T1 interactions versus time reveal an equilibrium fluctuation in the presence of water, leading to a less favorable 2'GMP-RNase T1 interaction energy, suggesting a possible relationship between picosecond fluctuations and inhibitor dissociation occurring in the millisecond time domain.

Endoribonucleases↗
PubMed1988

Influence of fried meat and fiber on cytochrome P-450 mediated activity and excretion of mutagens in rats.

Fried meat was included in the diet of Sprague-Dawley rats during one week. Ingested and excreted amounts of mutagenic activity were determined daily by the use of the Ames' Salmonella/mammalian microsome test on extracts of the diet, urine and feces. In addition, the effect of the fried meat on ethoxyresorufin-O-deethylase activity in the small intestine and in the liver was measured. The results were compared to those from a control group of rats receiving boiled instead of fried meat as their source of protein. The diet containing boiled meat was not mutagenic and none of the samples from the control group, neither urine nor feces, contained any mutagenicity. The activity of ethoxyresorufin O-deethylase in the small intestine was increased by fried meat whereas this enzyme activity in the liver was unaffected. O-deethylation of ethoxyresorufin is catalyzed by cytochrome P-450 dependent enzyme(s) and induction of the enzyme activity might indicate an increased metabolic activation of premutagens and precarcinogens in the intestine. It is not yet known whether the mutagens excreted by the animals receiving the fried meat diet represent unmetabolized dietary mutagens or are formed as a result of metabolic activation of compounds in fried food. Dietary fibers i.e. wheat bran, pectin, cellulose or ViSiblin were included in the above-described diets and were shown to lower the mutagenic activity in urine and feces of the rats. Pectin significantly increased the hepatic ethoxyresorufin-O-deethylase and decreased the 16 alpha-hydroxylation of 4-androstene-3,17-dione.

Animals↗
PubMed1988

Structural fluctuations of a helical polypeptide traversing a lipid bilayer.

Time-resolved fluorescence anisotropy (FA) measurements are reported for five helical bilayer-spanning henicosapeptides, each containing one tryptophan at sequence position 1, 6, 11, 16, or 21. The FA decay reflects two molecular processes in all cases: local internal fluctuations of the tryptophan side chain with a relaxation time of 200-500 ps, and motions of the whole polypeptide molecule with a relaxation time of 9-10 ns. The amplitudes of the fast fluctuation are largest at the helix ends and decrease toward the center of the helix. A similar observation was made for the helical polypeptides dissolved in organic solvents showing that the mobility gradient along the polypeptide sequence is an inherent property of the polypeptide helix and not due to the lipid bilayer. However, the amplitudes of the fast fluctuations can be modulated by the physical state of the lipid bilayer. With decreasing temperature, the internal mobility of the tryptophan in all positions decreases with an abrupt change at the lipid-phase transition. Concomitant molecular dynamics calculations indicate a correlation between the fast FA decay and conformational fluctuations within the helix. According to the simulation, the conformation of the polypeptide is on average predominantly helical, but actually the molecule can fluctuate between a variety of different substructures. The conformational fluctuations are largest at the helix ends and provide the free space required for rotation of the indole ring around the tryptophan side chain bonds.

Amino Acid Sequence↗
PubMed1988

Sonographic techniques in human in-vitro fertilization programmes.

The value of ultrasound in programmes of in-vitro fertilization is discussed. In order to reach the ovaries, the transvesical route was first introduced, and proved less invasive than laparoscopy. The periurethral route has also been used. The transvaginal approach, especially using a vaginal transducer with an attached needle guide, has attracted many IVF groups and is widely used today. Details of this method are presented. Ultrasound has also been used to assist in the replacement of embryos into the uterus, and the various methods are described.

Female↗
PubMed1988

Postantibiotic effect of aminoglycosides on gram-negative bacteria evaluated by a new method.

The in-vitro postantibiotic effect (PAE) of amikacin, gentamicin, netilmicin and tobramycin was investigated by a bioluminescent assay of bacterial ATP. Two strains each of Escherichia coli and Pseudomonas aeruginosa were exposed for 1 h to different concentrations of the aminoglycosides. The aminoglycoside was removed by a 10(-3) dilution, and regrowth of bacteria was followed at hourly intervals by monitoring bacterial ATP. This method simplified the PAE studies and made such studies possible at high aminoglycoside concentrations. The length of the PAE was dose-dependent for all the aminoglycosides studied. The PAEs ranged between three and seven hours for all four strains at the aminoglycoside concentrations normally reached in serum during standard dosing. The long PAE of aminoglycosides, especially after exposure to high drug concentrations, constitutes an argument in favour of administering aminoglycosides in higher-than-usual doses with longer intervals between doses. This proposal is also supported by recent pharmacokinetic, bacteriological and toxicity data.

Adenosine Triphosphate↗