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Biomedical subjects

J Brink

Publications and source records attributed to J Brink.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparison of induction chemotherapy before radiotherapy with radiotherapy only in patients with locally advanced squamous cell carcinoma of the lung. The Swedish Lung Cancer Study Group.

The aim of this randomised trial was to investigate the effect of induction chemotherapy before radiotherapy on survival in 302 patients with non-resectable squamous cell carcinoma of the lung. Radiotherapy, 56 Gy to the chest, was given to 154 patients and combined treatment, with chemotherapy preceding the radiotherapy, to 148 patients. Chemotherapy consisted of three courses of cisplatin (120 mg/m2) and etoposide (100 mg/m2 i.v. for 3 days) administered every fourth week. Median survival was 10.5 months in the radiotherapy arm and 11 months in the combined treatment arm. The 2-year survival rate was 17% in the radiotherapy arm and 21% in the combined treatment arm. Addition of chemotherapy seemed to significantly improve survival, according to the Cox multivariate analysis (P = 0.04), but as only a trend according to life-table analysis (P = 0.11). Chemotherapy also accomplished a trend towards improved local control (P = 0.08) and towards decreased metastatic disease (P = 0.10). 2 patients in the combined treatment arm, but none in the radiotherapy arm, died from toxicity. The conclusion was that the value of the chemotherapy used in this study was very modest, but the results strongly support further research for more efficient drugs and combinations.

Aged↗
PubMed1996

Performance of a slow-scan CCD camera for macromolecular imaging in a 400 kV electron cryomicroscope.

The feasibility and limitations of a 1024 x 1024 slow-scan charge-coupled device (CCD) camera were evaluated for imaging in a 400kV electron cryomicroscope. Catalase crystals and amorphous carbon film were used as test specimens. Using catalase crystals, it was found that the finite (24 microns) pixel size of the slow-scan CCD camera governs the ultimate resolution in the acquired images. For instance, spot-scan images of ice-embedded catalase crystals showed resolutions of 8 A and 4 A at effective magnifications of 67,000 x and 132,000 x, respectively. Using an amorphous carbon film, the damping effect of the modulation transfer function (MTF) of the slow-scan CCD camera on the specimen's Fourier spectrum relative to that of the photographic film was evaluated. The MTF of the slow-scan CCD camera fell off more rapidly compared to that of the photographic film and reached the value of 0.2 at the Nyquist frequency. Despite this attenuation, the signal-to-noise ratio of the CCD data, as determined from reflections of negatively-stained catalase crystals, was found to decrease to approximately 50% of that of photographic film data. The phases computed from images of the same negatively-stained catalase crystals recorded consecutively on both the slow-scan CCD camera and photographic film were found to be comparable to each other within 12 degrees. Ways of minimizing the effect of the MTF of the slow-scan CCD camera on the acquired images are also presented.

Animals↗
PubMed1996

Acute traumatic rupture of the thoracic aorta. A comparison of techniques.

Twenty-eight patients were treated for acute blunt thoracic aortic rupture at Groote Schuur Hospital between January 1984 and March 1994. Aortic arch ruptures occurred in 2 patients and were successfully repaired by means of hypothermic circulatory arrest. Descending aortic ruptures were repaired more safely by insertion of an interposition graft as opposed to direct suture reapproximation, and with the aid of partial heparinless bypass as opposed to simple aortic cross-clamping.

Accidents, Traffic↗
PubMed1996

Enteroscopy with enteroclysis.

The authors conclude that their experiences support the conclusion that the combination of enteroscopy and enterocysis is safe and offers quality small bowel examinations in a more comfortable and convenient single diagnostic setting. Although enteroclysis has identified bleeding sources in only 8% of patients who underwent this study, other lesions than angiodysplasia were confidently excluded in the remainder of patients. The combined procedure is well tolerated in the outpatient setting, more comfortable, and safer by decreasing radiation exposures than enteroclysis alone. Use of small bowel enteroscopy at an earlier stage in the evaluation of patients with obscure gastrointestinal bleeding increases cost effectiveness without compromising quality.

Barium Sulfate↗
PubMed1994

Measurement of slice sensitivity profiles in spiral CT.

In conventional computed tomography (CT), ramps, typically thin sheets of aluminum inclined at 45 degrees, are established tools for measurements of slice sensitivity profiles (SSP). In spiral CT, however, they yield inconsistent results for different positions along the longitudinal axis. It is explained herein how ramp profiles result as a superposition of true SSPs and artifacts, the artifacts being caused by the slice interpolation process due to the difficult interpolation condition in this particular geometry. In direct consequence, ramp tests yield spatially variant results. As an alternative tool for measuring the slice sensitivity profile, the use of a thin high-contrast sheet held between two disks which approximate the ideal test of a delta impulse in the longitudinal direction is suggested. Resulting SSPs are shown for both methods; the delta method, in agreement with theoretical predictions, provided smooth symmetrical SSPs independent of table position in agreement with theoretical predictions. It is concluded that ramps are inadequate test objects to determine SSPs in spiral CT.

Biophysical Phenomena↗
PubMed1993

Low-dose thickness measurement of glucose-embedded protein crystals by electron energy loss spectroscopy and STEM dark-field imaging.

Electron energy loss spectroscopy and dark-field imaging in a scanning transmission electron microscope were used to determine the thickness of glucose-embedded crotoxin complex crystals. The results demonstrate the feasibility of identifying protein crystals with a thickness of half a unit cell (12.8 nm) under low-dose and low-temperature conditions. The accuracy of this method is limited by the amount of surface coating of the crystal's embedding glucose used for preserving the high-resolution structure of the protein. The histogram of the crystal thickness distribution and the spread of the anticipated crystal thickness allow us to make an estimate of the uncertainty in the glucose layer thickness. This approach can be incorporated as part of the experimental procedure in the three-dimensional data collection for structure determination of protein crystals with variable thicknesses. The measurement can be done on areas approximately 200 nm in diameter so that crystals of suitable thickness can be pre-selected before the high-resolution data is recorded. Accurate determination of the crystal thickness will optimize the data collection efficiency by avoiding the collection and subsequent analysis of unmatchable data for the three-dimensional reconstruction.

Crotoxin↗
PubMed1992

The thickness determination of organic crystals under low dose conditions using electron energy loss spectroscopy.

In the 3-dimensional (3-D) reconstruction of protein crystals with variable thicknesses the electron images and diffraction patterns can only be merged if the crystal thickness is known. Measurement of the thickness using the ratio of the number of inelastically scattered electrons to the number of electrons in the zero loss peak can be accomplished with parallel electron energy loss spectrometry (PEELS). A theoretical analysis of the accuracy of the technique on paraffin crystals of different thicknesses is presented. Our experimental studies with paraffin crystals show the feasibility of measuring a single layer of 47A with good accuracy under low dose and low temperature conditions. A simple experimental apparatus is proposed to obtain thicknesses from small regions of unstained protein crystals prior to collecting the 3-D data sets from the unexposed area of the same crystal.

Crystallography↗
PubMed1992

Computer-controlled spot-scan imaging of crotoxin complex crystals with 400 keV electrons at near-atomic resolution.

400 keV electrons yield a better relative image contrast than 100 keV electrons for a beam-sensitive organic crystal when spot-scan imaging is used [J. Brink and W. Chiu, J. Microscopy 161 (1991) 279]. A FORTRAN 77 program has been written to operate the spot-scan imaging system on a computer workstation under the VMS operating system which is interfaced serially to the JEOL4000 electron microscope. We demonstrate the application of this implementation by imaging crotoxin complex crystals embedded in either vitreous ice or glucose to 2.5 A resolution. The intensity strength of the structure factors of this protein crystal are different at low (> 10 A) resolution but similar at high resolution (< 10 A) for the two embedding media as expected from their scattering contrast difference. Based on our experience as judged from the electron diffraction patterns of highly tilted crystals, flat crystals embedded in glucose can be readily obtained. Furthermore, our spot-scan imaging system also has the option of correcting the focus gradient that is present in images of tilted specimens.

Computers↗
PubMed1991

Contrast analysis of cryo-images of n-paraffin recorded at 400 kV out to 2.1 A resolution.

n-Paraffin was used as a test specimen for evaluating the relative merits of 400-kV versus 100-kV electron microscopy in recording data for electron crystallographic analysis of beam-sensitive materials. The parameter used for comparison, the relative contrast R, is the ratio of amplitudes from the computed Fourier transform of images and amplitudes from an electron diffraction pattern from the same crystal. R will thus be a measure of the contrast from an experimental image relative to that of a perfect image. Electron diffraction patterns and bright-field images were recorded at 400 kV at a specimen temperature of -167 degrees C. Using the flood-beam imaging technique the best R-value is 0.08 for all reflections in the resolution zone from 4 to 3 A. This value is equivalent to that found at 100 kV. In the resolution zone from 3 to 2A we have found R = 0.02. Using the spot-scan imaging technique, on the other hand, R was measured to be 0.42 for the reflections between 4- and 3-A resolution. This amount of relative contrast is 1.7 times that observed at 100 kV. Reflections at 3-2 A displayed an R-value of 0.05. Besides obtaining higher R-values when applying the spot-scan imaging technique at 400 kV, we observe a higher yield of images with isotropic diffraction and/or higher resolution reflections. Various contrast-attenuating factors, including the modulation transfer function of the photographic film and the cryo-holder, envelope functions for spatial and temporal coherence and lens and high-tension instabilities, the contrast transfer function and lastly the radiation damage effects, have been considered in interpreting the observed image contrast. Overall, use of 400 kV in combination with spot-scan does offer important improvements in contrast levels, which can be very useful in determining the three-dimensional structure from protein crystals.

Crystallography↗
PubMed1988

Electron microscopy and image analysis of the complexes I and V of the mitochondrial respiratory chain.

The results of Section IV can be summarized in a simple ATP synthase model. This model implies that either the alpha or the beta subunits must be closer to the membrane. The work of Gao and Bauerlein (1987) indicates that the alpha subunits are closer to the membrane. Although the overall structure is more or less clear, important questions need to be clarified. First, the number and the arrangement of the subunits in the F0 part must be known. Second, the exact shape of F1, and particularly the shape of the large subunits needs to be elucidated. On the basis of fluorescence resonance energy transfer measurements by McCarty and Hammes (1987), a model was presented showing large oblong subunits. Such 'banana-shaped' subunits, which are also presented in the many phantasy models (e.g. Walker et al., 1982), are very unlikely in view of the electron microscopical results, although the large subunits do not need to be exactly spherical. The third and most interesting central question is on the changes in the structure that take place during the different steps in the synthesis of ATP. It can now be taken as proven that the energy transmitted to the ATP synthase is used to induce a conformational change in the latter enzyme, in such a way as to bring about the energy-requiring dissociation of already synthesized ATP (Penefsky, 1985 and reviewed in Slater, 1987). But the way in which the three parts of the ATP synthase are involved is completely unknown. It is rather puzzling that such a long distance exists between the catalytic sites, which are on the interface of the alpha and beta subunits and the F0 part where the proton movements occur, which, according to Mitchell's theory (1961), is the driving force for the synthesis of ATP. Perhaps alternative mechanisms such as the collision hypothesis formulated by Herweijer et al. (1985) are more realistic in describing the mechanism of ATP synthesis. It would bring the complexes I and V close together, not only in the artificial way treated in this paper, but in a useful way for energy conversion.

Animals↗
PubMed1987

The structure of NADH:ubiquinone oxidoreductase from beef-heart mitochondria. Crystals containing an octameric arrangement of iron-sulphur protein fragments.

We have investigated the structure of two-dimensional crystals from preparations of NADH:ubiquinone oxidoreductase from beef-heart mitochondria. The crystal structure of these crystals was previously determined to be equivalent with two native enzyme molecules per unit cell, i.e. a p2 symmetry [Boekema, E. J., Van Heel, M. G. & Van Bruggen, E. F. J. (1984) Biochim. Biophys. Acta 787, 19-26]. However, the optical diffraction patterns of the crystals displayed a clear fourfold symmetry. A Fourier analysis carried out on the calculated diffraction pattern proved unambiguously that the crystal symmetry was p42(1)2. Following crystallographic rules the unit cell therefore contained eight identical molecules. As a consequence, only a subcomplex of the enzyme rather than the intact enzyme formed the crystal. Electron microscopy of isolated, single molecules of the iron-sulphur protein, a dissociation product of complex I, revealed the presence of square complexes with sides of approximately 15 nm. Since these complexes were indistinguishable from the building blocks (unit cells) of the two-dimensional crystals, the crystals could be composed of Fe-S protein fragments only. The nature of the fragments in the unit cell was probed by immuno-labelling with monovalent antibodies (Fab's), raised against the 75-kDa subunit from the Fe-S protein, followed by image analysis. We found at least four binding sites for the anti-(75-kDa subunit) Fab per unit cell, indicating the presence of at least four copies of the antigen. In order to account for these observations we postulate the hypothesis that the two-dimensional crystals obtained from complex I are composed of iron-sulphur protein molecules in an octameric arrangement.

Animals↗
PubMed1983

A simple procedure for the synthesis of [32P]phosphoenolpyruvate via the pyruvate kinase exchange reaction at equilibrium.

A one step procedure is presented for the preparation of [32P]phosphoenolpyruvate from [gamma-32P]ATP using pyruvate kinase. The reaction is carried out at chemical equilibrium and involves only an exchange of isotope between ATP and phosphoenolpyruvate. The initial phosphoenolpyruvate/ATP ratio in the reaction mixture determines the degree of 32P incorporation into phosphoenolpyruvate when isotopic equilibrium is achieved.

Adenosine Triphosphate↗
PubMed1976

Femoral shaft fractures in brain-injured children.

Thirty-nine head injured, initially comatose children with 44 femoral shaft fractures were treated by various methods. Thirty-two eventually ambulated. Tibial skeletal traction and skin traction were ineffective methods of management. Internal fixation or distal femoral traction are advised.

Adolescent↗