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M Wulff

Publications and source records attributed to M Wulff.

At least 19 recordsLinked to original sources
PubMed2003

First investigations of the kinetics of the topochemical reaction of p-formyl-trans-cinnamic acid by time-resolved X-ray diffraction.

Under UV irradiation p-formyl-trans-cinnamic acid (p-FCA) crystals in the beta-phase dimerise irreversibly to solid 4,4'-diformyl-beta-truxinic acid. The experimental conditions were chosen in such a way (non-aqueous environment and room temperature) that the product formed is amorphous. The kinetics of this bimolecular reaction, which has not yet been characterised, was investigated by picosecond time-resolved X-ray diffraction. From the experimental results a mechanism for this topochemical reaction is proposed including two observed time constants, one less than 100 ps and another of several seconds. The feasibility of investigating this class of substances by time-resolved X-ray diffraction from third generation synchrotron sources and future free-electron lasers is discussed.

Cinnamates↗
PubMed2002

Coitus-dependent and coitus-independent contraceptive methods in women and men.

OBJECTIVE: To study the use of contraceptives in Sweden. METHODS: Analysis of the population-based survey 'Sex in Sweden. On the Swedish sexual life 1996'. The survey was analyzed in relation to socio-demographic, lifestyle, sexual and behavioral characteristics as well as attitudes to, and evaluation of, personal experiences. The data included 2810 men and women between 18 and 74 years of age. The results were compared with a similar survey carried out in 1967. RESULTS: During the 30-year period between the 1967 and 1996 surveys, condom use more than halved and use of oral contraceptives increased by 6 percentage points. The decline in the use of condoms did not occur among teenagers but among all other age groups in both men and women. In 1996 the majority (72%) used a reliable contraceptive method, but 29% did not. Coitus-dependent methods were more frequently used by men and women who were below the age of 21, smoked, used alcohol simultaneously with coitus, had casual partners, were more highly educated, were breastfeeding, had coitus less frequently and among those who were most satisfied with their sexual life and their partner relationship. CONCLUSION: In order to increase the use of more reliable contraceptive methods, three crucial factors should be focused on in counselling and media campaigns: gender, age and the use of coitus-dependent/coitus-independent methods.

Adult↗
PubMed2001

A molecular movie at 1.8 A resolution displays the photocycle of photoactive yellow protein, a eubacterial blue-light receptor, from nanoseconds to seconds.

The photocycle of the bacterial blue-light photoreceptor, photoactive yellow protein, was stimulated by illumination of single crystals by a 7 ns laser pulse. The molecular events were recorded at high resolution by time-resolved X-ray Laue diffraction as they evolved in real time, from 1 ns to seconds after the laser pulse. The complex structural changes during the photocycle at ambient temperature are displayed in a movie of difference electron density maps relative to the dark state. The step critical to entry into the photocycle is identified as flipping of the carbonyl group of the 4-hydroxycinnamic acid chromophore into an adjacent, hydrophobic environment rather than the concomitant isomerization about the double bond of the chromophore tail. The structural perturbation generated at the chromophore propagates throughout the entire protein as a light-induced "protein quake" with its "epicenter" at the carbonyl moiety of the chromophore.

Bacterial Proteins↗
PubMed2001

Protein conformational relaxation and ligand migration in myoglobin: a nanosecond to millisecond molecular movie from time-resolved Laue X-ray diffraction.

A time-resolved Laue X-ray diffraction technique has been used to explore protein relaxation and ligand migration at room temperature following photolysis of a single crystal of carbon monoxymyoglobin. The CO ligand is photodissociated by a 7.5 ns laser pulse, and the subsequent structural changes are probed by 150 ps or 1 micros X-ray pulses at 14 laser/X-ray delay times, ranging from 1 ns to 1.9 ms. Very fast heme and protein relaxation involving the E and F helices is evident from the data at a 1 ns time delay. The photodissociated CO molecules are detected at two locations: at a distal pocket docking site and at the Xe 1 binding site in the proximal pocket. The population by CO of the primary, distal site peaks at a 1 ns time delay and decays to half the peak value in 70 ns. The secondary, proximal docking site reaches its highest occupancy of 20% at approximately 100 ns and has a half-life of approximately 10 micros. At approximately 100 ns, all CO molecules are accounted for within the protein: in one of these two docking sites or bound to the heme. Thereafter, the CO molecules migrate to the solvent from which they rebind to deoxymyoglobin in a bimolecular process with a second-order rate coefficient of 4.5 x 10(5) M(-1) s(-1). Our results also demonstrate that structural changes as small as 0.2 A and populations of CO docking sites of 10% can be detected by time-resolved X-ray diffraction.

Animals↗
PubMed2001

Visualizing photochemical dynamics in solution through picosecond x-ray scattering.

A photoexcited state of molecular iodine in solution is observed using diffuse x-ray scattering at a synchrotron source. The measured changes in the diffuse scattering profile were consistent with earlier models of iodine's photodissociation and geminate recombination reaction, for which the recombined A/A(') state has a 0.4 A greater interatomic spacing than the resting state and has a lifetime of 500 ps in CH2Cl2. This technique should find application in the study of increasingly complicated photochemical systems which undergo structural rearrangements following rapid photolysis.

Journal Article↗
PubMed2001

Picosecond X-ray diffraction probed transient structural changes in organic solids.

In this Letter, we report on the experimental characterization of the geometry of short-lived electronically excited states in organic solids by time-resolved x-ray diffraction. Here, the structure factor of the organic crystal is measured as a function of time. Since this technique gives complete structural information, it is a very useful tool for learning more about atom motions on the excited-state energy surface-"beyond" the broad band typical of conventional spectroscopy. Although we used molecular crystals rather than free molecules, the compounds show detectable transient structural changes on the ps to ns time scale in our study.

Journal Article↗
PubMed2001

Evaluation of the Intelisite capsule to deliver theophylline and frusemide tablets to the small intestine and colon.

The objective of the research was to establish the capability of the Intelisite capsule to deliver the probe drugs, theophylline and frusemide, in the form of split immediate release (IR) tablets, to the small intestine and colon. The two probe drugs were administered together in an open, random, three-way crossover study in eight healthy volunteers, comparing absorption following Intelisite delivery in the small bowel and colon to conventional IR dosing. Gamma scintigraphy was employed to monitor the gastrointestinal transit and activation of the Intelisite capsule. Standard pharmacokinetic parameters, and the percentage remaining in the capsules post defecation were determined. The Intelisite capsule was well tolerated in human volunteers and successfully activated on 15/16 occasions. Pharmacoscintigraphy showed internal marker release from the Intelisite capsule to be approximately 10-fold faster in the small intestine than in the colon. Theophylline and frusemide were both well absorbed following Intelisite activation in the small intestine, whereas complete colonic absorption was only observed in 1/7 subjects for theophylline, and 0/7 subjects for frusemide. The probe drugs were successfully delivered in particulate form from the Intelisite capsule in the small intestine and produced expected pharmacokinetic profiles. However drug release in the colon was incomplete and variable possibly due to: low water content, poor mixing, and a high loading dose.

Adult↗
PubMed2000

Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina.

OBJECTIVE: We sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina. BACKGROUND: Sildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs. METHODS: Two double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 microg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug. RESULTS: The effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, -52/-29 mm Hg) were greater than the effects of placebo plus ISMN on BP (-25/-15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (-36/-21 mm Hg) compared with placebo plus GTN (-26/-12 mm Hg; p < 0.01). CONCLUSIONS: Coadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Towards automated Laue data processing: application to the choice of optimal X-ray spectrum.

Laue data reduction has now reached a level of sophistication that allows nearly automated processing to be performed. The software described enables complete reduction of the data with essentially no user intervention, making Laue processing almost as straightforward as monochromatic data processing. Interactive work is limited to the indexing of only one Laue pattern. More importantly, it is shown that the data quality is substantially enhanced when soft-limited predictions are used. Further improvement obtained by taking advantage of the structure-factor amplitudes from a known closely related structure is described. To determine the most suitable type of insertion device to be used for time-resolved Laue crystallography, the technique described was applied to Laue data sets collected from photoactive yellow protein under identical conditions but with three different insertion devices: a wiggler, a broad-bandpass undulator and a single-line undulator. Although the optimal choice may ultimately be dictated by sample parameters (such as mosaic spread) and by the type of experiment (repeatable or non-repeatable reactions), the results here show that the use of single-line undulators will generally yield by far the best compromise between data quality, acquisition time and radiation damage.

Bacterial Proteins↗
PubMed1999

Solid state studies of drug-cyclodextrin inclusion complexes in PEG 6000 prepared by a new method.

The melting method was investigated as a possible method for producing drug-cyclodextrin (CD) inclusion compounds in a carrier. Various solid dispersions of alpha-, beta- and gamma-CD in polyethylene glycol (PEG) 6000 with and without the addition of 5% w/w indomethacin or griseofulvin were prepared using the original components. Characterisations of the samples included X-ray powder diffraction, modulated-temperature differential scanning calorimetry and dissolution tests by the paddle method according to USP XXI standard. Evidence of a complex between indomethacin and beta-CD in PEG 6000 was found. An indomethacin-gamma-CD complex formed a well defined phase in the PEG carrier, with tetragonal structure and unit cell parameters a=23.885(35) A and c=23.181(64) A. No complexation of indomethacin with alpha-CD, or with griseofulvin and beta-CD could be detected. It is suggested that competition between PEG and the drug for the binding to different CDs along with varying patterns of water loss from the CDs influence the inclusion reaction. The formation of complexes was accompanied by a decrease in the relative crystallinity of the dispersions. Dissolution tests showed that the CDs have a delaying effect on the release of indomethacin from PEG 6000 in the order alpha-CD<gamma-CD</=beta-CD.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

The effect of smelter work on fecundity.

Time to pregnancy (TTP) has been proposed as a screening instrument for the detection of environmental and occupational hazards to reproduction. Our aim was to determine whether reduced fecundity could be found among smelter workers and couples living near the smelter. The number of Months required to achieve a pregnancy was determined via a questionnaire, and TTP was analyzed using a logistic regression model with a cutoff at 12 months. No significant findings were found for a risk of having to wait for more than 12 months to achieve pregnancy because of occupational or environmental exposure. It could be that the exposure variables tested were not sensitive enough in detecting hazards to reproduction or that they were of minor importance. A tendency toward a prolonged TTP was found for couple living near the smelter.

Adult↗
PubMed1998

Energy transduction on the nanosecond time scale: early structural events in a xanthopsin photocycle.

Photoactive yellow protein (PYP) is a member of the xanthopsin family of eubacterial blue-light photoreceptors. On absorption of light, PYP enters a photocycle that ultimately transduces the energy contained in a light signal into an altered biological response. Nanosecond time-resolved x-ray crystallography was used to determine the structure of the short-lived, red-shifted, intermediate state denoted [pR], which develops within 1 nanosecond after photoelectronic excitation of the chromophore of PYP by absorption of light. The resulting structural model demonstrates that the [pR] state possesses the cis conformation of the 4-hydroxyl cinnamic thioester chromophore, and that the process of trans to cis isomerization is accompanied by the specific formation of new hydrogen bonds that replace those broken upon excitation of the chromophore. Regions of flexibility that compose the chromophore-binding pocket serve to lower the activation energy barrier between the dark state, denoted pG, and [pR], and help initiate entrance into the photocycle. Direct structural evidence is provided for the initial processes of transduction of light energy, which ultimately translate into a physiological signal.

Bacterial Proteins↗
PubMed1998

A comparison of two methods of securing an endotracheal tube.

While a variety of methods exist for securing an endotracheal tube (ETT), there has been little research on their safety and efficacy. This study aimed to test the equivalence of two methods in three critical care settings by randomly assigning patients to receive either the knot, which requires scissors or blade to remove the ETT tape, or the bow, which can be removed manually. These methods were evaluated by comparing ETT movement, malposition, dislodgement, inadvertent extubation, reduced skin integrity, the cutting of the pilot tube and nurse satisfaction. The 5-month study was conducted in three critical care settings in a large tertiary hospital. Of the 230 patients enrolled, 222 completed the trial. Results, based on a randomised, active control equivalence design, demonstrated the two methods to be equally effective with regard to ETT movement > 2 cm (knot = 21 per cent, bow = 19 per cent; 95 per cent confidence interval for the [2 per cent] difference-8 to 12.5 per cent). The incidence of ETT-related complications was similar for both methods. No pilot tubes were cut using either method. Nurses found that patient mouth care was easier and patient comfort and skin integrity enhanced with the bow method. On the other hand, nurses perceived the knot-tying method to be more secure and easier to apply. Given the equivalence of the two methods, the bow would seem preferable for reasons of safety and comfort.

Adult↗
PubMed1997

Infertility in an industrial setting--a population-based study from Northern Sweden.

OBJECTIVE: To analyze the possible environmental effects on infertility among couples living in the immediate neighborhood of a smelter and to study prevalence and risk factors of infertility as well as care seeking behavior among infertile couples in a random sample of a local population. METHODS: A questionnaire was distributed to 1,784 women between 25 and 44 years of age working at or living close to a copper smelter, and to women living further away from the smelter. The results were analyzed with a logistic regression. RESULTS: No environmental effects on infertility rates among couples living near the smelter were found. The prevalence of infertility, defined as having experienced a period of inability to conceive within 12 months of regular intercourse without contraception at some point in life, was the same between the neighbors and the reference population. The prevalence of primary and secondary infertility was 6% and 3%, respectively. Infertile women were characterized by having a significantly shorter education, OR 1.8 (CI 1.2-2.7), compared to women who had not experienced any fertility problems. Risk estimates for not seeking health care when having a low socio-economic status was OR 2.1 (CI 1.0-4.4) compared to those with a higher socio-economic status. CONCLUSION: No environmental effects on infertility could be demonstrated. Infertile women were characterized by having a shorter education compared to the non infertile, and women with lower socio-economic status were less prone to seek help.

Adult↗
PubMed1996

Photolysis of the carbon monoxide complex of myoglobin: nanosecond time-resolved crystallography.

The biological activity of macromolecules is accompanied by rapid structural changes. The photosensitivity of the carbon monoxide complex of myoglobin was used at the European Synchrotron Radiation Facility to obtain pulsed, Laue x-ray diffraction data with nanosecond time resolution during the process of heme and protein relaxation after carbon monoxide photodissociation and during rebinding. These time-resolved experiments reveal the structures of myoglobin photoproducts, provide a structural foundation to spectroscopic results and molecular dynamics calculations, and demonstrate that time-resolved macromolecular crystallography can elucidate the structural bases of biochemical mechanisms on the nanosecond time scale.

Carbon Monoxide↗
PubMed1996

The structure of the Escherichia coli EF-Tu.EF-Ts complex at 2.5 A resolution.

The crystal structure of the EF-Tu.EF-Ts complex from Escherichia coli has been determined to a resolution of 2.5 A. The complex contains two subunits of each of the elongation factors. The two EF-Ts molecules form a tight dimer, but there is little contact between the two EF-Tu molecules. The interaction of EF-Ts with EF-Tu results principally in the disruption of the Mg2+ ion binding site, thereby reducing the affinity of EF-Tu for guanine nucleotides.

Amino Acid Sequence↗
PubMed1996

Congenital malformations in the vicinity of a smelter in Northern Sweden, 1973-1990.

The objective was to evaluate the rates of congenital malformation in children born in a population living around a smelter and to employees at the smelter, in a community in northern Sweden. By means of record linkage of the birth register and various registers of congenital malformations, a retrospective study of a birth cohort according to place of parental residence and employment was carried out to assess rates of congenital malformation occurring between 1973-1990. Neither a general, nor specific, significantly increased risk of congenital malformation was seen in the 2724 children born to women living close to the smelter or to employees of the smelter compared with the 15191 children in the reference population. No increased risk could be ascertained although there are reservations concerning the small sample size of the study group.

Case-Control Studies↗